natriuretic-peptide--brain and Hypertension--Pulmonary

Topics: Biomarkers; Diagnostic Tests, Routine; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Pulmonary Arterial Hypertension; Scleroderma, Systemic

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Topics: Familial Primary Pulmonary Hypertension; Hemodynamics; Humans; Hypertension, Pulmonary; Iron Deficiencies; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Arterial Hypertension

There is significant controversy relating to whether chronic thromboembolic pulmonary hypertension (CTEPH) can be treated with pulmonary arterial hypertension- (PAH-) targeted therapies and which therapy is the optimal choice for patients. A large number of randomized controlled trials (RCTs) have compared PAH-targeted therapies with placebo or conventional therapies. In this study, we aimed to compare all of the PAH-targeted medications that are used to treat CTEPH and rank their efficacy by the application of network meta-analysis (NMA).. We searched PubMed, EMBASE, Web of Science, the Cochrane Central Register, https://clinicaltrials.gov, and who.int/trialsearch/, for relevant RCTs published up to January 2020. In addition to traditional meta-analysis, we also performed NMA in our systematic review, as deployed in a previous protocol (PROSPERO: CRD42020173765).. Our study identified eight eligible RCTs that evaluated seven PAH-targeted therapies in 703 patients with CTEPH. NMA revealed that riociguat was ranked first as the most optimized therapy for ameliorating the 6-minute walk distance with a probability of 80.4%. Bosentan was significantly better than others with regard to reducing brain natriuretic peptide/N-terminal pro-B-type natriuretic peptide with a probability of 84.3%. Sildenafil was identified as the best drug in terms of improving the New York Heart Association/World Health Organization functional class with a probability of 87.3%. Treprostinil and macitentan were more beneficial than other drugs in reducing pulmonary vascular resistance and lowering the incidence of clinical worsening with probabilities of 86.2% and 79.2%, respectively.. Analysis revealed positive advantages for the use of PAH-targeted drugs in patients with CTEPH. Overall, treprostinil and riociguat were superior to all other PAH-targeted medications in most of the outcomes investigated.

Topics: Antihypertensive Agents; Bosentan; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Network Meta-Analysis; Sildenafil Citrate; Treatment Outcome; Vasodilator Agents

To systematically review the diagnostic accuracy of brain natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in bronchopulmonary dysplasia (BPD) and BPD-pulmonary hypertension (PH).. PubMed, Embase, the Web of Science, and the Cochrane Library were searched in March 2019. We included studies that evaluated BNP or NT-proBNP in preterm neonates as a marker for predicting BPD, BPD or death, and BPD-PH.. Nine studies evaluating NT-proBNP/BNP were included. The quality of evidence was low, using GRADE criteria. The diagnostic accuracy of NT-proBNP and BNP for diagnosing BPD-PH showed high sensitivity and specificity in infants with BPD. Lower sensitivities and specificities of NT-proBNP and BNP were reported for predicting BPD, BPD or death, compared with that for BPD-PH.. Low quality evidence suggests that NT-proBNP and BNP have adequate diagnostic accuracy for diagnosing and monitoring BPD-PH and may be used to triage patients to receive an echocardiogram.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Natriuretic Peptide, Brain; Peptide Fragments; Reference Standards; ROC Curve; Sensitivity and Specificity

Pulmonary arterial hypertension (PAH) is a major complication of systemic sclerosis (SSc) and screening is recommended for a timely initiation of disease-targeted drug therapy to modify disease progression. Patients with SSc-PAH have a better prognosis when detected and treated early. The PAH can occur in all disease stages and subsets of SSc. Regular screening tests, which are indicative for PAH, e.g. echocardiography, diffusion capacity, brain natriuretic protein (BNP) and a 6-min walking test, are recommended to enhance the suspicion, since clinical symptoms are unspecific and occur late in the course of PAH. In patients with suspected PAH, the diagnosis should be confirmed by right heart catheterization. A multidisciplinary approach in expert centres including rheumatologists and respiratory physicians and cardiologists specialized in pulmonary hypertension is mandatory for management of patients with SSc at risk for or with manifest pulmonary arterial hypertension.

Topics: Cardiac Catheterization; Early Diagnosis; Early Medical Intervention; Echocardiography; Exercise Test; Humans; Hypertension, Pulmonary; Interdisciplinary Communication; Intersectoral Collaboration; Natriuretic Peptide, Brain; Prognosis; Pulmonary Diffusing Capacity; Scleroderma, Systemic

Pulmonary hypertension has emerged as a major cause of morbidity and mortality in patients with hemoglobinopathies and chronic hemolytic anemias. These hematological diseases include - but are not limited to - sickle cell disease (SCD), thalassemia, paroxysmal nocturnal hematuria, and hereditary spherocytosis. Although most studies have been based on the use of echocardiography as a screening tool for pulmonary hypertension as opposed to the gold standard of right heart catheterization for definitive diagnosis, the association between chronic hemolytic anemia and pulmonary hypertension is evident. Studies have shown that patients with SCD and a tricuspid regurgitant velocity (TRV) ≥ 2.5 m/sec are at increased risk of pulmonary hypertension and are at increased mortality risk. Additional markers of risk of pulmonary hypertension and increased mortality include a pro-BNP >160 pg/mL combined with a 6-min walk distance of <333 m. There is currently a lack of concrete data to support the use of targeted oral pulmonary arterial hypertension therapy in chronic hemolytic anemia. As a result, management is generally targeted towards medical optimization of the underlying anemia. This literature review aims to discuss the pathophysiology, diagnostic and prognostic tools, recent studies and current protocols that are essential in guiding management of pulmonary hypertension in chronic hemolytic anemias.

Topics: Anemia, Hemolytic; Anemia, Sickle Cell; Cardiac Catheterization; Chronic Disease; Echocardiography; Exercise Tolerance; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Prognosis; Risk Factors; Walk Test

This study aims to review pediatric pulmonary hypertension (PH) by comparing the guidelines of the European Society of Cardiology (ESC)/European Respiratory Society (ERS), the American Heart Association (AHA)/American Thoracic Society (ATS), and the European Pediatric Pulmonary Vascular Disease Network (EPPVDN). All three sets of guidelines define PH as having a mean pulmonary artery pressure of ≥25 mmHg and accept the validity of the World Health Organization (WHO) classification system. Every child with a high index of suspicion for PH should undergo an initial work-up of chest X-rays, electrocardiography, and echocardiography. The AHA/ATS guidelines emphasize the necessity of cardiac catheterization and hemodynamic studies. As mentioned in the AHA/ATS guidelines, the symptoms and tests that can detect PH include right ventricle failure, WHO functional class, syncope, echocardiography findings, hemodynamic data, brain natriuretic peptide (BNP)/N-terminal pro-BNP, the 6-min walk test, and cardiopulmonary exercise tests. The EPPVDN guidelines refer to positive acute vasoreactivity test results and growth as risk factors. All three guidelines highlight the importance of treating and following affected children in specialized centers and recommend calcium channel blockers as a first-line treatment in children (aged >12 months) who have a positive acute vasoreactivity test. Children with PH have distinct clinical features. In order to overcome the controversies related to the optimal management of pediatric PH, well-designed clinical studies should be carried out on a large cohort of affected children.

Topics: Calcium Channel Blockers; Cardiac Catheterization; Child; Echocardiography; Electrocardiography; Hemodynamics; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Predictive Value of Tests; Radiography, Thoracic; Randomized Controlled Trials as Topic; Syncope

Riociguat is a soluble guanylate cyclase stimulator that has been approved for the treatment of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension following pulmonary endarterectomy. Riociguat is administered using an 8-week individual dose-adjustment scheme whereby a patient initially receives riociguat 1.0 mg three times daily (tid), and the dose is then increased every 2 weeks in the absence of hypotension, indicated by systolic blood pressure measurements and symptoms, up to a maximum dose of 2.5 mg tid. The established riociguat dose-adjustment scheme allows the dose of riociguat to be individually optimized in terms of tolerability and efficacy. The majority of patients in the phase III clinical trials and their long-term extension phases achieved the maximum riociguat dose, whereas some patients remained on lower doses. There is evidence that these patients may experience benefits at riociguat doses lower than 2.5 mg tid, with improvement in exercise capacity being observed after only 2-4 weeks of treatment in the phase III studies and in the exploratory 1.5 mg-maximum patient group of PATENT-1. This review aims to provide an overview of the rationale behind the riociguat dose-adjustment scheme and examine its application to both clinical trials and real-life clinical practice.

Topics: Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Enzyme Activators; Exercise Tolerance; Guanylate Cyclase; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Pulmonary Embolism; Pyrazoles; Pyrimidines; Vascular Resistance; Walk Test

Topics: Biomarkers; Cost-Benefit Analysis; Early Diagnosis; Echocardiography, Doppler; False Positive Reactions; Genetic Testing; Humans; Hypertension, Pulmonary; Mass Screening; Natriuretic Peptide, Brain; Respiratory Function Tests; Scleroderma, Systemic

This study aims to evaluate the survival of patients with systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) by a systematic review and meta-analysis.. Studies were searched from MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trial and Scopus databases, and were selected according to the inclusion and exclusion criteria. Two independent reviewers extracted data from selected studies. Quality assessments were also performed using the Newcastle-Ottawa Scale. All pooled analyses were conducted both for random-effects model and fixed-effects model. Subgroup analysis and sensitivity analysis were conducted to investigate the origins of heterogeneity. Publication bias was evaluated using Begg's funnel plots and Egger's test.. Six studies encompassing 323 patients with SLE-associated PAH were included in the meta-analysis. The pooled 1-, 3- and 5-year survival rates were 88% (95% CI, 0.80-0.93), 81% (95% CI, 0.67-0.90) and 68% (95% CI, 0.52-0.80), respectively. No significant publication bias was shown. WHO Functional class (Fc) III/IV was found to be an independent prognostic factor of mortality. Higher mean pulmonary arterial pressure (mPAP), higher pulmonary vascular resistance (PVR), lower six minutes walking distance (6MWD), higher brain natriuretic peptide (BNP) and higher N-terminal proBNP (NT-proBNP) level were also related to poor survival.. The long-term survival of patients with SLE-associated PAH is poor, which is worth paying greater clinical and academic attention. This study suggested that early diagnosis and management are recommended in patients with SLE-associated PAH for a better outcome of survival.

Topics: Early Diagnosis; Humans; Hypertension, Pulmonary; Lupus Erythematosus, Systemic; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Topics: Adult; Diagnosis, Differential; Disease Progression; Female; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments

Significant advances in the treatment of pulmonary arterial hypertension (PAH) over the last two decades have led to the introduction of multiple classes of oral therapy, but the disease remains devastating for many patients. Disease progression, in spite of oral monotherapy, is a major problem, and alternative therapy, such as infusion of prostacyclins, is cumbersome and carries considerable potential morbidity. Use of combination oral therapy, including drugs from both the endothelin receptor antagonist and phosphodiesterase-5 inhibitor classes, has increased, and there is some evidence to support this approach. Given the multiple options now available in pulmonary hypertension (PH) therapy, biomarkers to guide treatment decisions could be helpful. Here, we review the evidence for and against the clinical use of molecular biomarkers relevant to PH pathogenesis, emphasizing assayable markers that may also inform more rational selection of agents that influence pathways targeted by treatment. We emphasize the interactive nature of changes in mediators and messengers, such as endothelin-1, prostacyclin, brain natriuretic peptide (which has demonstrated biomarker utility), nitric oxide derivatives, and cyclic guanosine monophosphate, which play important roles in processes central to progression of PAH, such as vascular remodeling, vasoconstriction, and maladaptive right ventricular changes, and are relevant to its therapy. Accordingly, we propose that the identification and use of a molecular biomarker panel that assays these molecules in parallel and serially might, if validated, better inform unique patient phenotypes, prognosis, and the rational selection and titration of combination oral and other therapy in individual patients with PH/PAH.

Topics: Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Biomarkers; Cyclic AMP; Cyclic GMP; Endothelin-1; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Nitric Oxide; S-Nitrosothiols; Treatment Outcome

Despite the introduction of targeted therapies in pediatric pulmonary arterial hypertension (PAH), prognosis remains poor. For the definition of treatment strategies and guidelines, there is a high need for an evidence-based recapitulation of prognostic factors. The aim of this study was to identify and evaluate prognostic factors in pediatric PAH by a systematic review of the literature and to summarize the prognostic value of currently reported prognostic factors using meta-analysis.. Medline, EMBASE and Cochrane Library were searched on April 1st 2014 to identify original studies that described predictors of mortality or lung-transplantation exclusively in children with PAH. 1053 citations were identified, of which 25 were included for further analysis. Hazard ratios (HR) and 95% confidence intervals were extracted from the papers. For variables studied in at least three non-overlapping cohorts, a combined HR was calculated using random-effects meta-analysis. WHO functional class (WHO-FC, HR 2.7), (N-terminal pro-) brain natriuretic peptide ([NT-pro]BNP, HR 3.2), mean right atrial pressure (mRAP, HR 1.1), cardiac index (HR 0.7), indexed pulmonary vascular resistance (PVRi, HR 1.3) and acute vasodilator response (HR 0.3) were identified as significant prognostic factors (p ≤ 0.001).. This systematic review combined with separate meta-analyses shows that WHO-FC, (NT-pro)BNP, mRAP, PVRi, cardiac index and acute vasodilator response are consistently reported prognostic factors for outcome in pediatric PAH. These variables are useful clinical tools to assess prognosis and should be incorporated in treatment strategies and guidelines for children with PAH.

Topics: Biomarkers; Child; Child, Preschool; Heart Rate; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Pediatric pulmonary arterial hypertension (PAH) is an uncommon disease that can occur in neonates, infants, and children, and is associated with high morbidity and mortality. Despite advances in treatment strategies over the last two decades, the underlying structural and functional changes to the pulmonary arterial circulation are progressive and lead eventually to right heart failure. The management of PAH in children is complex due not only to the developmental aspects but also because most evidence-based practices derive from adult PAH studies. As such, the pediatric clinician would be greatly aided by specific characteristics (biomarkers) objectively measured in children with PAH to determine appropriate clinical management. This review highlights the current state of biomarkers in pediatric PAH and looks forward to potential biomarkers, and makes several recommendations for their use and interpretation.

Topics: Atrial Natriuretic Factor; Biomarkers; Breath Tests; Cell-Derived Microparticles; Child; Cytokines; Echocardiography; Endothelial Cells; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging; MicroRNAs; Natriuretic Peptide, Brain; Peptide Fragments; Tomography, X-Ray Computed; Vascular Remodeling

Lung diseases are one of the most frequent causes of pulmonary hypertension (PH). The development of PH influences the course of lung disease, worsening the clinical symptoms and prognosis. According to the most recent publications, PH in the course of lung diseases develops as a result of both "parenchymal" and vascular pathology, in the patients with genetic predisposition. Prolonged infection (especially viral one) may be an additional promoting factor. Right heart catheterization (RHC), which is an invasive procedure, is the only objective method of diagnosing PH. According to the latest recommendations, the management algorithm of PH and coexisting interstitial lung disease is based on RHC and the results of pulmonary function tests. Majority of the patients develop mild PH in the course of advanced lung disease. Best treatment of underlying lung pathology combined with long term oxygen treatment is recommended in this group. In case of severe PH (mean resting pulmonary artery pressure (mPAP) ≥ 35 mm Hg) the alternate cause of PH has to be sought. PAH-specific drugs use should be limited to patients with severe PH participating in clinical trials. In this review, the value of various non-invasive methods (echocardiography, radiological examination, exercise capacity and brain natriuretic peptides assessment) in the process of screening for PH is presented, and the results of recent randomized clinical trials with PAH-specific drugs in patients with diffuse parenchymal lung diseases are discussed.

Topics: Cardiac Catheterization; Clinical Trials as Topic; Echocardiography; Exercise; Female; Humans; Hypertension, Pulmonary; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Prognosis; Respiratory Function Tests

Pulmonary hypertension (PH) is a life-threatening disease with a high mortality rate and a broad variety of underlying etiologies. The current golden standard for diagnosing PH and monitoring efficiency of treatment is right heart catheterization. As an alternative, serum biomarkers have been suggested. Cardiac troponin T (TnT), brain natriuretic peptide (BNP), and NT-proBNP seem the most potential. The aim of this systematic review was to evaluate the current literature on the prognostic value of these biomarkers in children with PH and their usefulness as a diagnostic tool. A systematic literature search yielded 14 studies on patients ≤18 years with proven PH with (NT-pro)BNP or TnT as primary outcome. TnT is suggested to be a promising biomarker, but its usefulness in clinical practice has not been proven. The levels of (NT-pro)BNP seemed to be reliable within one PH category, but differed significantly between categories. NT-proBNP showed a good correlation with mortality and might have a prognostic value.. The lack of absolute levels makes (NT-pro)BNP unsuitable as a diagnostic marker, but in view of the relative changes, it could be used to monitor patients. Further investigation should explore differences in normal (NT-pro)BNP levels between the different categories of PH.. • Pulmonary hypertension is a life-threatening disease. Diagnosis can be challenging in children; the current diagnostic options-right heart catheterization and echocardiography-are invasive and/or investigator-dependent procedures. • Biomarkers could be useful in this context because they are investigator independent and easy to obtain through blood samples. Brain natriuretic peptide (BNP) and its N-terminal cleavage product (NT-proBNP) seem to be the most promising. The value of these biomarkers in the diagnostic approach of PH has already been investigated in adults, with promising results. Pediatric studies are still scarce. What is new: • The levels of BNP and NT-proBNP in pediatric patients differ strongly between the different categories of PH. Within the same category, the levels are more or less equal. • The relative changes could render them a prognostic marker in the follow-up of a certain individual patient. At this moment there is not enough evidence to rely on BNP or NT-proBNP in clinical treatment of patients with PH.

Topics: Biomarkers; Child; Global Health; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Survival Rate

Pulmonary arterial hypertension (PAH) is a frequent complication in connective tissue diseases (CTD), especially in systemic sclerosis (SSc), and is associated with a high degree of morbidity and mortality. We undertook a systematic review for the screening tests for CTD-PAH.. A systematic literature search of PAH in CTD was performed in available databases through June 2012. Our evaluation of diagnostic tests was focused on patients with PAH confirmed by right heart catheterization (RHC).. The search resulted in 2805 titles and 838 abstracts. Our final inclusion encompassed 22 articles-six of which were case-control studies and 16 were cohort studies. Twelve studies assessed the tricuspid regurgitation velocity (VTR) or equivalent right ventricular systolic pressure (RVSP) using transthoracic echocardiogram (TTE) as a threshold for RHC in patients suspected as having PAH. The screening threshold for RHC was VTR from >2.73 to >3.16 m/s without symptoms or 2.5-3.0m/s with symptoms and resulted in 20-67% of patients having RHC-proven PAH. Three studies looked at pulmonary function tests and found that a low lung diffusing capacity for carbon monoxide (DLCO) (45-70% of predicted) is associated with a 5.6-7.4% development of PAH, and a decline in DLCO% is associated with an increase in the specificity (for DLCO ≤ 60%, spec = 45%; and for DLCO ≤ 50%, spec = 90%) for PAH. Five studies assessed N-terminal prohormone of brain natriuretic peptide (NT-ProBNP), where a cutoff >239 pg/ml had a sensitivity of 90-100%.. Our systematic review revealed that most evidence exists for TTE, pulmonary function tests, and NT-ProBNP for screening and diagnosis of SSc-PAH; however, more robust studies are needed.

Topics: Connective Tissue Diseases; Echocardiography; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Respiratory Function Tests; Sensitivity and Specificity

To evaluate new development in the utility of brain natriuretic peptide and N-Terminal brain natriuretic peptide (BNP/NT-Pro-BNP) in the management of various cardiovascular diseases. The determination of plasma BNP levels has an established role in the discrimination of pulmonary oedema from other causes of acute dyspnoea, and there is increasing evidence of the utility of BNP/NT-Pro-BNP assay both as a prognostic tool in chronic heart failure and as a means of guiding therapy in heart failure patients aged below 70 years.. Findings have substantially extended the clinical utility of BNP/NT-Pro-BNP assay. In heart failure with preserved left ventricular ejection fraction, BNP elevation may also facilitate diagnosis, although its precise utility is uncertain.In the acute catecholamine-induced myocardial inflammatory condition of Tako-Tsubo cardiomyopathy (TTC), BNP/NT-Pro-BNP elevations are marked and persist for at least 3 months, despite the absence of pulmonary oedema. In TTC, BNP/NT-Pro-BNP therefore serves as an ancillary diagnostic measure as well as a marker of recovery. Among other conditions in which BNP assay may provide prognostic information are atrial fibrillation (in which the extent of elevation predicts thromboembolic risk) and pulmonary hypertension.. BNP/NT-Pro-BNP assay has widespread utility as an adjunct to cardiovascular disease diagnosis and management.

Topics: Aging; Biomarkers; Heart Diseases; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Stroke Volume

Pulmonary hypertension is common in bronchopulmonary dysplasia and is associated with increased mortality and morbidity. This pulmonary hypertension is due to abnormal microvascular development and pulmonary vascular remodeling resulting in reduced cross-sectional area of pulmonary vasculature. The epidemiology, etiology, clinical features, diagnosis, suggested management, and outcomes of pulmonary hypertension in the setting of bronchopulmonary dysplasia are reviewed. In summary, pulmonary hypertension is noted in a fifth of extremely low birth weight infants, primarily those with moderate or severe bronchopulmonary dysplasia, and persists to discharge in many infants. Diagnosis is generally by echocardiography, and some infants require cardiac catheterization to identify associated anatomic cardiac lesions or systemic-pulmonary collaterals, pulmonary venous obstruction or myocardial dysfunction. Serial echocardiography and B-type natriuretic peptide measurement may be useful for following the course of pulmonary hypertension. Currently, there is not much evidence to indicate optimal management approaches, but many clinicians maintain oxygen saturation in the range of 91 to 95%, avoiding hypoxia and hyperoxia, and often provide inhaled nitric oxide, sometimes combined with sildenafil, prostacyclin, or its analogs, and occasionally endothelin-receptor antagonists.

Topics: Bronchopulmonary Dysplasia; Humans; Hypertension, Pulmonary; Infant, Extremely Low Birth Weight; Infant, Newborn; Natriuretic Peptide, Brain; Oxygen

The development of pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) is multifactorial with a number of biomarkers serving as mediators of neurohormonal activation [B-type natriuretic peptide (BNP) and its N-terminal-pro-fragment (NT-proBNP)], endothelial dysfunction [asymmetric dimethylarginine (ADMA)] and cellular proliferation [vascular endothelial growth factor (VEGF)].. We systematically reviewed the literature for trials studying the role of these biomarkers in the clinical evaluation, prognosis and management of patients with PAH related to CHD (CHD-PAH).. Twenty-six studies were included in the systematic review, involving a total of 1113 patients with CHD-PAH. These patients had higher BNP, NT-proBNP and ADMA levels and higher VEGF expression when compared with healthy controls. Baseline and serial values of plasma levels of natriuretic peptides were shown to be significant predictors of survival. ADMA concentration was elevated in patients with CHD-PAH when compared with patients with simple CHD without PAH, whereas VEGF expression was particularly high in patients with CHD and persistent PAH after corrective surgery of the underlying heart disease.. Right heart dysfunction, endothelial inflammation and proliferation are mirrored by plasma levels of the corresponding biomarkers among patients with CHD-PAH. There is early evidence to suggest that natriuretic peptides, in particular, may be a simple and effective tool for determining prognosis and timing for therapeutic interventions in patients with CHD-PAH.

Topics: Animals; Biomarkers; Cross-Sectional Studies; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Prospective Studies; Retrospective Studies; Vascular Endothelial Growth Factor A

Pulmonary hypertension is frequent in advanced chronic respiratory diseases, with an estimated prevalence at the time of pulmonary transplantation of 30-50 % in idiopathic pulmonary fibrosis, 30-50 % in chronic obstructive pulmonary disease, 50 % in combined pulmonary fibrosis and emphysema, 75 % in sarcoidosis, and more than 75 % of cases in pulmonary Langerhans cell histiocytosis. Histologic features include varying degrees of pulmonary arterial remodeling (prominent), vascular rarefaction (emphysema), fibrosis or specific involvement of the pulmonary arteries (idiopathic pulmonary fibrosis, sarcoidosis, lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis), in situ thrombosis, and frequently associated involvement of the pulmonary veins (idiopathic pulmonary fibrosis, sarcoidosis). Pulmonary hypertension is usually detected using echocardiography with Doppler, however right heart catheterisation is required to confirm precapillary pulmonary hypertension defined by pulmonary artery pressure ≥ 25 mm Hg, with pulmonary artery wedge pressure ≤ 15 mm Hg. When present, it is associated with decreased exercise capacity and worse mortality. Pulmonary hypertension in chronic respiratory disease is almost invariably multifactorial; hypoxia is one of its main determinants, however supplemental oxygen therapy rarely reverses pulmonary hypertension. Management of pulmonary hypertension in chronic respiratory disease is mostly based on the optimal treatment of the underlying disease. Available data do not support the use of drug therapies specific for pulmonary hypertension in the setting of chronic respiratory diseases, however very few clinical studies have been conducted so far specifically in this context.

Topics: Antihypertensive Agents; Biomarkers; Cardiac Catheterization; Chronic Disease; Dyspnea; Echocardiography, Doppler; Exercise Tolerance; Humans; Hypertension, Pulmonary; Lung Transplantation; Natriuretic Peptide, Brain; Oxygen Inhalation Therapy; Prognosis; Respiratory Tract Diseases; Severity of Illness Index; Vascular Resistance; Vasodilator Agents

Pulmonary arterial hypertension (PAH) is a classical complication of connective tissue diseases (CTD), particularly in systemic sclerosis (SSc), systemic lupus erythematous (SLE) or mixed connective tissue diseases (MCTD). The prevalence of PAH in SSc, as measured by right heart catheterization (RHC), is estimated between 7.85 to 13%. The detection of PAH in SSc is based on trans-thoracic echocardiography. Early detection in pulmonary hypertension is the best way to improve the survival in these diseases. In the DETECT study, 19% of high-risk PAH patients with SSc (SSc diagnosed less than 3 years before and DLco<60% predicted) have PAH as measured by RHC. Specific treatments for PAH are less efficient in PAH related to SSc than in idiopathic PAH. The main characteristic of PAH related to CTD other than SSc is a good response to immunosuppressive treatment, with an improvement in 50% of cases in SLE or MCTD. The prognosis of PAH associated with CTD seem to improve with the diversification of treatments available, but remains reserved. Therapeutic combinations and new molecules should allow to improve the prognosis.

Topics: Antibodies; Anticoagulants; Antihypertensive Agents; Atrial Septum; Biomarkers; Cardiac Catheterization; Connective Tissue Diseases; Diuretics; Drug Therapy, Combination; Echocardiography; Electrocardiography; Endothelin Receptor Antagonists; Exercise Test; Humans; Hypertension, Pulmonary; Immunosuppressive Agents; Lung Transplantation; Magnetic Resonance Imaging, Cine; Natriuretic Peptide, Brain; Oxygen Inhalation Therapy; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Prognosis; Respiratory Function Tests

Portopulmonary hypertension (PoPH) is defined by the combination of portal hypertension and precapillary pulmonary hypertension (mPAP ≥ 25 mmHg, PCWP < 15 mmHg and PVR > 3 Wood units). PoPH is characterised by pathobiological mechanisms that are similar to other forms of pulmonary arterial hypertension. Prevalence of PoPH is estimated at 0.5-5% among patients with portal hypertension with or without cirrhosis. Treatment strategies most commonly employed for PoPH patients are based on recommendations for idiopathic PAH management. Indeed, the choice of specific PAH treatment must take account the severity of the underlying liver disease. Prognosis of PoPH patients is dependent on both the severity of PAH and of the underlying liver disease. PoPH may be a contraindication for orthotopic liver transplantation (OLT) if mean pulmonary arterial pressure is > 35 mmHg associated with severe right ventricular dysfunction or high level of pulmonary vascular resistance (> 3-4 Wood units). Bridge therapy with specific PAH therapies should be considered in those patients in an attempt to improve pulmonary hemodynamic and thereby allow OLT with acceptable risk. Recent data suggest that stabilize, improve or cure PoPH seems to be possible by combining specific PAH therapies and liver transplantation in selected patients. Clinical and experimental evidences suggest that IFN therapy may be a possible risk factor for PAH.

Topics: Algorithms; Anticoagulants; Antihypertensive Agents; Antiviral Agents; Biomarkers; Calcium Channel Blockers; Cardiac Catheterization; Diagnostic Imaging; Electrocardiography; Humans; Hypertension, Pulmonary; Interferon-alpha; Interferon-beta; Liver Diseases; Liver Transplantation; Natriuretic Peptide, Brain; Oxygen Inhalation Therapy; Phosphodiesterase 5 Inhibitors; Postoperative Care; Preoperative Care; Prevalence; Telangiectasia, Hereditary Hemorrhagic

The optimal timing of valve surgery remains controversial. Biomarkers can be serially monitored and are objective laboratory measurements. Plasma B-type natriuretic peptide (BNP) and its N-terminal pro-form are well known predictors in heart failure. Diastolic stretch induces cardiomyocyte BNP expression in volume-loaded conditions like aortic or mitral regurgitation (MR) or pressure-loaded conditions like aortic stenosis (AS). Here, we review the value of natriuretic peptide measurements in valve disease. Cardiac decompensation is reflected by increased BNP in AS and in MR. Repeated marked increases in natriuretic peptides are a potential indication for valve replacement in severe asymptomatic AS with normal ejection fraction and exercise test results. High BNP level also predicts postoperative outcome. Increased BNP level is associated with low-flow AS, impaired left ventricular longitudinal strain, and myocardial fibrosis. The BNP ratio to the reference value for age and sex incrementally predicts mortality in AS. Increased BNP reflects the hemodynamic consequences of MR and is associated with exercise-induced pulmonary-arterial hypertension and reduced contractile reserve. In severe primary MR, increased and serially increasing BNP or N-terminal pro-form BNP might be helpful in guiding early mitral replacement. In conclusion, baseline (N-terminal pro-form) BNP should be obtained in all severe valve disease patients and interpreted together with clinical and echocardiography findings. Very high BNP values are associated with increased mortality and should lead to close monitoring peri- and postoperatively. Progressively increasing BNP in asymptomatic patients points to advancing valve disease. BNP adds important incremental prognostic information that is useful for valve patient management and for optimal timing of surgery in particular.

Topics: Age Factors; Aortic Valve Insufficiency; Aortic Valve Stenosis; Biomarkers; Female; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Male; Mitral Valve Insufficiency; Mitral Valve Stenosis; Natriuretic Peptide, Brain; Sex Factors; Tricuspid Valve Insufficiency

Pulmonary hypertension (PH) is a hemodynamic condition that has a poor prognosis and can lead to right-sided heart failure. It may result from common diseases such as left-sided heart or lung disease or may present as the rare entity of idiopathic pulmonary arterial hypertension. Biomarkers that specifically indicate the pathologic mechanism, the severity of the disease, and the treatment response would be ideal tools for the management of PH. In this review, markers related to heart failure, inflammation, hemostasis, remodeling, and endothelial cell-smooth muscle cell interaction are discussed, and their limitations are emphasized. Anemia, hypocarbia, elevated uric acid, and C-reactive protein levels are unspecific markers of disease severity. Brain natriuretic peptide and N-terminal fragment of pro-brain natriuretic peptide have been recommended in current guidelines, whereas other prognostic markers, such as growth differentiation factor-15, osteopontin, and red cell distribution width, are emerging. Chemokines of the CC family and matrix metalloproteases have been linked to the vascular pathologic mechanisms, and new markers such as apelin have been described. Circulating endothelial and progenitor cells have received much attention as markers of disease activity, but with controversial findings. A lack of standards for cell isolation and characterization methods and differences in the pathologic mechanisms of the investigated patients may have contributed to the discrepancies. In conclusion, although several promising markers have been identified over the past few years, the development of more specific markers, standardization, and prospective validation are warranted.

Topics: Biomarkers; Endothelial Cells; Familial Primary Pulmonary Hypertension; Growth Differentiation Factor 15; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Osteopontin; Peptide Fragments; Prognosis

Pulmonary arterial hypertension (PAH) is a progressive vasculopathy that is advanced by the time symptoms develop. As symptoms are nonspecific and the condition uncommon, continued progression toward end-stage disease occurs for an average of 2 years between symptom onset and diagnosis. There is need for earlier diagnosis and treatment, as most patients are severely symptomatic when diagnosed and their mortality is high despite therapy. Screening can help; however, it is not straightforward due to the diversity of patient profiles and lack of sufficiently accurate tools. Echocardiography, currently the best available screening tool, lacks both sensitivity and specificity. The low prevalence of PAH renders many screening tools unfit for purpose. However, this may be overcome, in some instances, by using enrichment tools to preselect screening populations. The majority of data are available for systemic sclerosis. A recent study has demonstrated how lung function can be used to enrich PAH prevalence in a systemic sclerosis population. A screening bundle then selects patients for right heart catheterisation with improved rates of sensitivity compared to current guidelines.

Topics: Algorithms; Biomarkers; Diagnostic Techniques and Procedures; Disease Progression; Early Diagnosis; Echocardiography; Exercise Test; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Lung; Natriuretic Peptide, Brain; Peptide Fragments; Practice Guidelines as Topic; Predictive Value of Tests; Prognosis; Respiratory Function Tests; Risk Factors; Scleroderma, Systemic; Time Factors

Brain natriuretic peptide (BNP) and N-terminal brain natriuretic peptide (NT-proBNP) are important biomarkers for pediatric cardiovascular diseases. Peptide levels are associated with age and gender. Current studies have shown that BNP and NT-proBNP are valuable in the diagnosis of heart failure, with a high specificity and sensitivity. They also contribute to differentiating heart failure from acute respiratory distress induced by simple pulmonary factors. In addition, BNP and NT-proBNP are useful in the evaluation of disease severity and treatment guidance in children with pulmonary hypertension, cardiomyopathy and Kawasaki disease. Current limitations include the relatively small sample size of the study, the detection method and a range of normal values that are not completely uniform.

Topics: Cardiomyopathies; Cardiovascular Diseases; Child; Dyspnea; Familial Primary Pulmonary Hypertension; Heart Failure; Humans; Hypertension, Pulmonary; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments

The right ventricle (RV) is in charge of pumping blood to the lungs for oxygenation. Pulmonary arterial hypertension (PAH) is characterized by high pulmonary vascular resistance and vascular remodeling, which results in a striking increase in RV afterload and subsequent failure. There is still unexploited potential for therapies that directly target the RV with the aim of supporting and protecting the right side of the heart, striving to prolong survival in patients with PAH.

Topics: Exercise Tolerance; Health Status Indicators; Heart Failure; Heart Ventricles; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging, Cine; Natriuretic Peptide, Brain; Oxygen Consumption; Ultrasonography; Ventricular Function, Left; Ventricular Function, Right; Ventricular Remodeling

Pulmonary hypertension (PH) is characterized hemodynamically by significantly elevated pulmonary artery pressure, which if sustained can result in clinical deterioration due to progressive right-sided heart failure and death. Establishing the etiology of PH in a patient before treatment is imperative. Effective evidence-based therapeutic agents for treating PH have been developed. However, appropriately powered, randomized trials in PH associated with left-sided heart failure are sparse, and those that have been performed have shown no benefit or harm. An improved understanding of the pathophysiology, definition, and development of new therapies for treating PH associated with left-sided heart failure is urgently needed.

Topics: Calcium Channel Blockers; Endothelins; Heart Diseases; Heart Failure; Hemodynamics; Humans; Hypertension, Pulmonary; Natriuretic Agents; Natriuretic Peptide, Brain; Phosphodiesterase 5 Inhibitors; Prognosis; Stroke Volume; Ventricular Function, Left

Effective management of patients with pulmonary arterial hypertension (PAH) requires comprehensive prognostic evaluation in order to determine optimal management strategies. Although a number of clinical and hemodynamic parameters linked to PAH prognosis have been identified, some are associated with significant limitations (eg, invasive techniques, subjective measures). There is a need for noninvasive and objective measures to be established that function as biomarkers for the diagnosis and assessment of disease prognosis, and that determine response to therapy in patients with PAH. Reflecting the highly complex etiology of the disease, a large number of potential biomarkers have been, and continue to be, investigated in PAH, including those reflecting right heart function, endothelial dysfunction, and markers of inflammation and second organ failure. However, it has become clear that scientifically interesting biomarkers may not necessarily be clinically useful. Of the range of biomarkers investigated in PAH to date, only brain natriuretic peptide and its N-terminal cleavage product have been included as prognostic parameters in treatment guidelines. It is unlikely that any single biomarker will provide all the relevant information required for an individual patient, and the potential for combining markers is currently of considerable interest. Future studies are required to determine the optimal combination of existing and emerging biomarkers in the clinical setting.

Topics: Biomarkers; Creatinine; Endothelium, Vascular; Familial Primary Pulmonary Hypertension; Heart Failure; Humans; Hypertension, Pulmonary; Inflammation; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Prognosis; Sodium; Troponin T

The long-term prognosis for patients with pulmonary arterial hypertension (PAH) remains poor, despite advances in treatment options that have been made in the past few decades. Recent evidence suggests that World Health Organization functional class I or II patients have significantly better long-term survival rates than patients in higher functional classes, thus providing a rationale for earlier diagnosis and treatment of PAH. However, early diagnosis is challenging and there is frequently a delay between symptom onset and diagnosis. Screening programmes play an important role in PAH detection and expert opinion favours echocardiographic screening of asymptomatic patients who may be predisposed to the development of PAH (i.e. those with systemic sclerosis or sickle cell disease), although current guidelines only recommend annual echocardiographic screening in symptomatic patients. This article reviews the currently available screening programmes, including their limitations, and describes alternative screening approaches that may identify more effectively those patients who require right heart catheterisation for a definitive PAH diagnosis.

Topics: Anemia, Sickle Cell; Antihypertensive Agents; Bosentan; Early Diagnosis; Echocardiography, Doppler; Exercise Test; Humans; Hypertension, Pulmonary; Mass Screening; Natriuretic Peptide, Brain; Peptide Fragments; Piperazines; Practice Guidelines as Topic; Purines; Respiratory Function Tests; Risk Factors; Scleroderma, Systemic; Sildenafil Citrate; Sulfonamides; Sulfones; Vasodilator Agents

Pulmonary hypertension (PH) is a well-recognized complication of sarcoidosis. Patients with sarcoidosis-associated PH (SAPH) have poorer functional status and greater supplemental oxygen requirements than sarcoidosis patients without PH, and are more likely to be listed for lung transplantation. PH is an independent risk factor for mortality in sarcoidosis patients awaiting lung transplantation. The pathophysiology of SAPH is complex, with multiple mechanisms contributing to pathogenesis, including the fibrous destruction of the pulmonary vascular bed, extrinsic compression of the central pulmonary vessels and an intrinsic vasculopathy. Recognition of SAPH may be delayed as it can be masked by the clinical picture of underlying pulmonary sarcoidosis, and right heart catheter remains the gold-standard for diagnosis. Management of SAPH is based on reversal of resting hypoxaemia, treatment of comorbidities and treatment of the underlying sarcoidosis. The use of corticosteroids in SAPH is controversial. Specific PH therapy is not routinely recommended in SAPH as there are no successful placebo-controlled trials, although there is limited data to suggest that endothelin receptor antagonists and phosphodiesterase-5 inhibitors may be useful.

Topics: Cardiomyopathies; Endothelin-1; Humans; Hypertension, Pulmonary; Lung; Natriuretic Peptide, Brain; Sarcoidosis, Pulmonary; Ultrasonography; Vasoconstriction

The review provides an update of the epidemiology, pathogenesis, risk factors, screening and treatment of pulmonary arterial hypertension in systemic sclerosis.. Several recent studies have investigated the utility of several noninvasive screening methods and the propagation of new treatments promise the clinician better outcomes than the current median survival time of 1 year for patients with scleroderma-related pulmonary arterial hypertension.. Pulmonary hypertension is a frequent cause of morbidity and mortality in patients with systemic sclerosis. This review discusses the recent changes in the classification of pulmonary hypertension, especially the significance for the rheumatologist. A high clinical suspicion should be maintained, even in early scleroderma. Despite progress in echocardiography and biomarkers, right heart catheterization remains the only test that can diagnose pulmonary hypertension and differentiate pulmonary veno-occlusive disease from pulmonary arterial hypertension. The differentiation of these causes of pulmonary hypertension in the scleroderma patient is essential because the initiation of pulmonary vasodilators in veno-occlusive disease often leads to increased mortality. The role of screening with serum biomarkers and noninvasive testing remains controversial, and in this review we discuss the controversies and new recommendations in detail.

Topics: Biomarkers; Cardiac Catheterization; Echocardiography; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Respiratory Function Tests; Risk Factors; Scleroderma, Systemic

A biological marker can be defined as any substance that can be objectively measured and evaluated as an indicator of a normal biological process, a pathogenic process or pharmacological responses to a therapeutic intervention. In pulmonary hypertension (PH), in addition to routine markers (hemodynamic and functional), there are a growing number of biomarkers that allow an increasingly comprehensive approach to knowledge of susceptibility to this disease and to diagnosis, prognosis and treatment response. These markers can be both constitutive (genetic) and disease-related (related to right ventricular failure, such as BMP/NT-proBNP, endothelial dysfunction, such as endothelin-1, or inflammation, such as certain cytokines and chemokines). Novel insights in genomics and proteomics may allow major advances in this field.

Topics: Biomarkers; Blood Proteins; Bone Morphogenetic Protein Receptors, Type II; Cytokines; Endothelins; Genetic Predisposition to Disease; Humans; Hypertension, Pulmonary; Intracellular Signaling Peptides and Proteins; Natriuretic Peptide, Brain; Peptide Fragments; Polymorphism, Single Nucleotide; Prognosis; Troponin T

The prevalence of primary (hereditary) hemochromatosis and secondary iron overload (hemosiderosis) is reaching epidemic levels worldwide. Iron-overload leads to excessive iron deposition in a wide variety of tissues, including the heart and endocrine tissues.. Iron-overload cardiomyopathy is the primary determinant of survival in patients with secondary iron overload, while also being a leading cause of morbidity and mortality in patients with primary hemochromatosis. Iron-induced cardiovascular injury also occurs in acute iron toxicosis (iron poisoning), myocardial ischemia-reperfusion injury, cardiomyopathy associated with Friedreich ataxia, and vascular dysfunction. The mainstay therapies for iron overload associated with primary hemochromatosis and secondary iron overload is phlebotomy and iron chelation therapy, respectively. L-type Ca(2+) channels provide a high-capacity pathway for ferrous (Fe(2+)) uptake into cardiomyocytes in iron-overload conditions; calcium channel blockers may represent a new therapeutic tool to reduce the toxic effects of excess iron.. Iron-overload cardiomyopathy is a an important and potentially reversible cause of heart failure at an international scale and involves diastolic dysfunction, increased susceptibility to arrhythmias and a late-stage dilated cardiomyopathy. The early diagnosis of iron-overload cardiomyopathy is critical since the cardiac dysfunction is reversible if effective therapy is introduced before the onset of overt heart failure.

Topics: Anemia; Antioxidants; Biopsy; Calcium Channel Blockers; Cardiomyopathies; Chelation Therapy; Echocardiography; Endocardium; Endothelium, Vascular; Ferritins; Genetic Testing; Humans; Hypertension, Pulmonary; Iron Overload; Magnetic Resonance Imaging, Cine; Natriuretic Peptide, Brain; Phlebotomy; Transferrin; Ventricular Dysfunction, Right

The diagnosis and assessment of pulmonary arterial hypertension is a rapidly evolving area, with changes occurring in the definition of the disease, screening and diagnostic techniques, and staging and follow-up assessment. The definition of pulmonary hypertension has been simplified, and is now based on currently available evidence. There has been substantial progress in advancing the imaging techniques and biomarkers used to screen patients for the disease and to follow up their response to therapy. The importance of accurate assessment of right ventricular function in following up the clinical course and response to therapy is more fully appreciated. As new therapies are developed for pulmonary arterial hypertension, screening, prompt diagnosis, and accurate assessment of disease severity become increasingly important. A clear definition of pulmonary hypertension and the development of a rational approach to diagnostic assessment and follow-up using both conventional and new tools will be essential to deriving maximal benefit from our expanding therapeutic armamentarium.

Topics: Antihypertensive Agents; Blood Pressure; Echocardiography, Doppler; Epoprostenol; Exercise Tolerance; Hemodynamics; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Reference Values; Ventricular Function, Right

Chronic obstructive pulmonary disease (COPD) is commonly associated with heart failure. Individuals with COPD have a 4.5-fold greater risk of developing heart failure than those without. The sensitivity and specificity of clinical judgment in the diagnosis of heart failure in patients with COPD can be enhanced by biological markers such as B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide. Correct interpretation of imaging results (mainly echocardiographic findings) and lung function tests can also help establish the co-occurrence of both conditions. There is little evidence on the management of patients with COPD and heart failure, although treatment of COPD undeniably affects the clinical course of patients with heart failure and viceversa.

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Bronchodilator Agents; C-Reactive Protein; Combined Modality Therapy; Contraindications; Drug Interactions; Heart Failure; Heart Function Tests; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Oxygen Inhalation Therapy; Peptide Fragments; Pulmonary Disease, Chronic Obstructive; Pulmonary Heart Disease; Respiration, Artificial; Respiratory Function Tests

Sodium-uretic peptides (SUP) are the main humoral system opposing pathological remodeling of vascular bed in diseases of cardiovascular system and kidneys. In the paper, pathogenetic and clinical significance of the cerebral SUP in pulmonary arterial hypertension, including the one associated with interstitial diseases of the lungs.

Topics: Animals; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Natriuretic Peptide, Brain

It is known that prognosis of pulmonary hypertension (PH), especially connective tissue disease related PH (CTD-PH), is serious. CTD-PH is caused by not only pulmonary arterial hypertension, but also interstitial pneumonitis, hypoxia, chronic thromboembolism of pulmonary artery, or left heart diseases. Recently, prognosis of PH is improved by progress of diagnostic measures including echocardiography and development of effective vasodilators. However, early diagnosis of PH is necessary for further improvement of the prognosis. Previous reports have shown that diffusion lung capacity for carbon monoxide (DLco) is reduced in the early phase of PH, and we have shown that serum lactate dehydrogenase level is also elevated in this phase. Furthermore, we have been studying significance of stress echocardiography. Therefore, if reduced DLco or LDH elevation are recognized, follow up of laboratory data such as blood levels of KL-6, NT-proBNP, D-dimer, echocardiography, high resolution CT of the lung, in addition to clinical findings are important for prediction of PH.

Topics: Biomarkers; Carbon Monoxide; Chronic Disease; Connective Tissue Diseases; Early Diagnosis; Echocardiography; Humans; Hypertension, Pulmonary; L-Lactate Dehydrogenase; Lung; Lung Diseases, Interstitial; Lung Volume Measurements; Mucin-1; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Embolism; Tomography, X-Ray Computed

Vascular disease is present in every patient with scleroderma and is a major source of morbidity and mortality. There is a subset of patients who will develop severe and sometimes life-threatening vascular events. We have good evidence that an insult to the microvasculature occurs early in the disease course, but there is a subset of patients who have an ongoing chronic process, the end result of which are events such as digital loss and pulmonary arterial hypertension. The ability to detect this process at an early stage by simple means would be of great value as our ability to treat these vascular complications improves with time. We have a significant amount of evidence of vascular perturbation from studies of peripheral blood in scleroderma, but know very little about the ability of these biomarkers to predict vascular outcomes. In this review, we will critically assess our current knowledge of the use of biomarkers of vascular disease in scleroderma and the possible directions of future research in this area.

Topics: Biomarkers; Carbon Dioxide; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Diffusing Capacity; Scleroderma, Systemic; Vascular Endothelial Growth Factor A

Mild-to-moderate pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD); such a complication is associated with increased risks of exacerbation and decreased survival. Pulmonary hypertension usually worsens during exercise, sleep and exacerbation. Pulmonary vascular remodelling in COPD is the main cause of increase in pulmonary artery pressure and is thought to result from the combined effects of hypoxia, inflammation and loss of capillaries in severe emphysema. A small proportion of COPD patients may present with "out-of-proportion" pulmonary hypertension, defined by a mean pulmonary artery pressure >35-40 mmHg (normal is no more than 20 mmHg) and a relatively preserved lung function (with low to normal arterial carbon dioxide tension) that cannot explain prominent dyspnoea and fatigue. The prevalence of out-of-proportion pulmonary hypertension in COPD is estimated to be very close to the prevalence of idiopathic pulmonary arterial hypertension. Cor pulmonale, defined as right ventricular hypertrophy and dilatation secondary to pulmonary hypertension caused by respiratory disorders, is common. More studies are needed to define the contribution of cor pulmonale to decreased exercise capacity in COPD. These studies should include improved imaging techniques and biomarkers, such as the B-type natriuretic peptide and exercise testing protocols with gas exchange measurements. The effects of drugs used in pulmonary arterial hypertension should be tested in chronic obstructive pulmonary disease patients with severe pulmonary hypertension. In the meantime, the treatment of cor pulmonale in chronic obstructive pulmonary disease continues to rest on supplemental oxygen and a variety of measures aimed at the relief of airway obstruction.

Topics: Biomarkers; Disease Progression; Emphysema; Humans; Hypertension, Pulmonary; Hypoxia; Lung; Lung Transplantation; Natriuretic Peptide, Brain; Oxygen; Prognosis; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Medicine; Sleep

In contrast to their established role in the evaluation of acute dyspnea in emergency department (ED) patients, applications of B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP) in patients outside of the ED are less well defined. A PubMed-based electronic and hand search for articles dealing with BNP and NT-proBNP in settings other than the ED was performed. We found that currently available evidence is sufficient to support the use of BNP and NT-proBNP in four cardiovascular settings outside of the ED: i) evaluation of patients with suspected heart failure (HF) referred from primary care, ii) risk stratification in patients with HF, iii) risk stratification in stable coronary artery disease, and iv) risk stratification in pulmonary artery hypertension. Recent studies indicate that BNP and NT-proBNP might also be helpful in guiding therapy in patients with chronic HF. Despite active research in many additional fields, the use of BNP/NT-proBNP in other settings is not yet based on solid evidence and, therefore, seems not to be useful.

Topics: Biomarkers; Coronary Disease; Dyspnea; Emergency Service, Hospital; Heart Failure; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments

Recent discoveries in the disease pathophysiology of pulmonary arterial hypertension have been translated into effective therapies tested in clinical trials. The studies have focused on surrogate and intermediate end points, thought to reflect quantity and quality of life, respectively. The authors present the necessary requirements for establishing the reliability and validity of such end points before they may be used dependably. The authors also review the available data, strengths, and weaknesses of potential end points in pulmonary arterial hypertension.

Topics: Biomarkers; Exercise Test; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Quality of Life; Randomized Controlled Trials as Topic; Reproducibility of Results; Treatment Outcome

Pulmonary hypertension (PH) has long been recognized as a complication of chronic respiratory disease. Recent studies have highlighted the adverse impact PH has on the clinical course of these conditions and have cast doubt on the role of hypoxia in their pathogenesis. Clinicians should carefully consider the possibility of PH during the diagnostic evaluation of chronic respiratory disorders. The usefulness of pharmacologic therapy directed toward PH remains to be determined.

Topics: Chronic Disease; Comorbidity; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Natriuretic Peptide, Brain; Oxygen Inhalation Therapy; Positive-Pressure Respiration; Pulmonary Disease, Chronic Obstructive; Pulmonary Wedge Pressure; Respiratory Tract Diseases; Sleep Apnea Syndromes

B-type natriuretic peptide (BNP) and N-terminal-pro-BNP (NTpBNP) have a major role in screening and diagnosis of cardiac disease and monitoring of the treatment response in children and adults. This review discusses the evidence underpinning the potential benefits of these natriuretic peptides in neonatology. They may serve as a useful adjunct to echocardiography in the diagnosis of patent ductus arteriosus and its response to treatment and the diagnosis of persistent pulmonary hypertension of the newborn. However, more work is needed to explore the possible roles of BNP/NTpBNP in the management of sepsis and monitoring of cardiac performance in neonates.

Topics: Biomarkers; Cardiovascular Diseases; Ductus Arteriosus, Patent; Humans; Hypertension, Pulmonary; Infant, Newborn; Natriuretic Peptide, Brain; Peptide Fragments; Reference Values

Hypoxia and endothelial dysfunction play a central role in the development of pulmonary hypertension. Cor pulmonale is a maladaptive response to pulmonary hypertension. The presence of peripheral edema in cor pulmonale is almost invariably associated with hypercapnia. Correction of abnormalities of gas exchange and ventilation can ameliorate pulmonary hypertension and improve survival. This review focuses on new information about the pathogenesis and treatment of pulmonary hypertension in COPD including information derived from lung volume reduction surgery, the role of brain natriuretic peptide, exhaled nitric oxide for diagnosis, and the treatment of cor pulmonale with recently available specific pulmonary vasodilators.

Topics: Chronic Disease; Comorbidity; Humans; Hypertension, Pulmonary; Natriuretic Agents; Natriuretic Peptide, Brain; Nitric Oxide; Phlebotomy; Pulmonary Disease, Chronic Obstructive; Pulmonary Heart Disease

Pulmonary hypertension (PH) is a serious disease with a poor prognosis. Pulmonary arterial hypertension (PAH) is distinguished from other forms of PHT. The leading symptom is exertional dyspnea. Patients with chronic severe PAH commonly die of right heart failure. PH has a complex heterogeneous aetiology, and precapillary forms are distinguished from postcapillary PH. A number of pathogenetically important signaling pathways such as the endothelin, nitric oxide and prostacyclin pathways have been identified, which constitute the target of the currently approved treatment options. Transthoracic echocardiography is the most important noninvasive diagnostic method. In addition, 6-min walking distance and measurement of serum markers, such as brain natriuretic peptide (BNP), are diagnostically useful and of prognostic significance.

Topics: Diagnosis, Differential; Echocardiography; Ergometry; Exercise Test; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Prognosis

With a quickly growing range of therapeutic options precise prognostic stratification became particularly important for clinical decision making in patients with pulmonary arterial hypertension (PAH). Assessment of disease-specific functional class remains the simplest method and is a fairly reliable way of assessing severity of PAH, and current guidelines recommend a therapeutic algorithm based on functional class evaluation. Six-minute walk is the most widely used test assessing exercise tolerance both in clinical practice and in clinical trials testing new therapies in PAH. Right heart catheterization with a vasoreactivity test is mandatory to identify a subgroup that has good long-term prognosis when treated with calcium channel blockers alone. Echocardiographic variables of documented prognostic value in PAH are not those directly correlated with pulmonary arterial pressure (PAP). Instead, the presence of pericardial effusion, enlarged right atrium, and elevated Doppler index of right ventricular performance have been the most consistently reported signs of poor prognosis. Low or decreasing brain natriuretic peptide (BNP) suggests a good outcome whereas troponin T leak persisting despite therapy is a poor prognostic sign. Biomarkers seem particularly useful for noninvasive follow-up of patients with PAH, and due to simplicity and low costs may successfully compete with echocardiography.

Topics: Biomarkers; Cardiac Catheterization; Echocardiography, Doppler; Exercise Test; Hemodynamics; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Severity of Illness Index; Troponin T

Brain or B-type natriuretic peptide (BNP) is one of the new biomarkers employed within the last decade to help clarify difficult cardiovascular problems. Plasma BNP is elevated in cardiac ventricular dysfunction and plays a key role in protecting the body from volume overload by maintaining renal function and sodium balance. Studies in patients with pulmonary arterial hypertension (PAH) have demonstrated that plasma BNP levels are raised proportionally to the extent of right ventricular (RV) dysfunction. There is growing evidence that BNP may be a potential biomarker for PAH in screening for occult disease, diagnostic evaluation, prognosis, and estimating a response to therapy. Additionally, augmentation of the natriuretic peptide system through exogenous administration of BNP or by preventing its degradation may be a promising option for the management of decompensated RV failure. Because plasma BNP levels rise in a variety of cardiopulmonary conditions and are affected by several physiological factors, BNP interpretation must not occur in isolation but rather within the context of good clinical judgment.

Topics: Biomarkers; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Ventricular Dysfunction, Right

Determining whether a patient's symptoms are the result of heart or lung disease requires an understanding of the influence of pulmonary venous hypertension on lung function. Herein, we describe the effects of acute and chronic elevations of pulmonary venous pressure on the mechanical and gas-exchanging properties of the lung. The mechanisms responsible for various symptoms of congestive heart failure are described, and the significance of sleep-disordered breathing in patients with heart disease is considered. While the initial clinical evaluation of patients with dyspnea is imprecise, measurement of B-type natriuretic peptide levels may prove useful in this setting.

Topics: Adult; Aged; Biomarkers; Biopsy, Needle; Diagnosis, Differential; Dyspnea; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension, Pulmonary; Immunohistochemistry; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Edema; Radiography, Thoracic; Respiratory Function Tests; Risk Assessment; Severity of Illness Index

It is well-recognized that atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are raised in conditions with ventricular volume and pressure overload. In addition to this established role in left ventricular congestive cardiac failure, there is good evidence that BNP has a diagnostic role in right ventricular (RV) dysfunction and pulmonary arterial hypertension (PAH). For example, BNP levels can be used to differentiate between dyspneic patients with pure respiratory defects and those with RV dysfunction. Studies in patients with PAH have demonstrated significant correlations between BNP levels and mean pulmonary arterial pressure as well as pulmonary vascular resistance. Additionally, BNP has a prognostic role in patients with RV pressure overload and pulmonary hypertension, and it offers a noninvasive test that can be used to guide therapy in patients with PAH. However, although measured plasma proBNP levels are raised in conditions with RV overload, its biological significance is still not well-understood. In this article, we review the general physiologic and potential therapeutic role of natriuretic peptides in respiratory disease, RV dysfunction, and PAH. Furthermore, we assess the various clues toward natriuretic peptide action coming from laboratory studies. ANP and BNP knockout mice develop cardiac fibrosis and hypertrophy. Potentiation of the natriuretic pathway has been shown to reduce cardiac hypertrophy and PAH. This is likely to take place as a result of increased intracellular cyclic guanosine monophosphate levels and subsequent pulmonary vasorelaxant activity. In view of this evidence, there may be a rationale for the therapeutic use of recombinant BNP or neutral endopeptidase inhibitors under conditions of RV dysfunction and PAH.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cardiomegaly; Fibrosis; Heart Ventricles; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Ventricular Dysfunction, Right; Ventricular Pressure

Topics: Atrial Natriuretic Factor; Biomarkers; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Prognosis

B-type natriuretic Peptide (BNP) is elevated in conditions with ventricular volume and pressure overload. The physiological, diagnostic and therapeutic role of BNP in right ventricular (RV) dysfunction and pulmonary arterial hypertension (PAH) are reviewed in this article. BNP levels can be used to differentiate between breathless patients with a respiratory disease and those with PAH. BNP has been shown to correlate with mean pulmonary arterial pressure and pulmonary vascular resistance in patients with PAH, whether primary or secondary. BNP is also a predictor of mortality in patients with primary pulmonary hypertension. These are important clinical implications in that a non-invasive blood test may be used to identify patients who require more invasive procedures (such as cardiac catheterization). There is increasing evidence that BNP or NT-proBNP measurements may also be used to guide therapy (e.g. pulmonary vasorelaxants) in PAH. Enhancement of the natriuretic peptide pathway has been shown to reduce cardiac hypertrophy and PAH and hence, there may be therapeutic potential via recombinant BNP or neutral endopeptidase inhibitors in RV dysfunction and PAH.

Topics: Fibrosis; Heart Ventricles; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Peptide; Vasodilation; Ventricular Dysfunction, Right

A HORMONE REVEALING VENTRICULAR DYSFUNCTION: B-type natriuretic peptide or Brain natriuretic peptide (BNP) is a neurohormone secreted by the ventricular myocytes in response to volume expansion and pressure overload. It is a sensitive marker of ventricular dysfunction in symptomatic and asymptomatic patients, and its dosage is correlated with the severity of the dysfunction. INDICATION FOR ITS DOSAGE IN HEART FAILURE: Since the results of recent studies, many authors recommend its routine use in heart failure, in order to confirm the diagnosis in difficult cases, assess severity, prognosis and the efficacy of treatment. Such use requires that the results of these studies be known and that the threshold value be adapted according to the age, concomitant diseases and indication of the dosage. OTHER AFFECTIONS: Its diagnostic and prognostic interest in acute coronary syndromes and hypertension is presently being studied.

Topics: Acute Disease; Angina, Unstable; Chronic Disease; Clinical Trials as Topic; Diagnosis, Differential; Dyspnea; Emergencies; Female; Heart Diseases; Heart Failure; Humans; Hypertension; Hypertension, Pulmonary; Male; Myocardial Infarction; Natriuretic Peptide, Brain; Prognosis; Risk Factors; ROC Curve; Sensitivity and Specificity; Troponin; Ventricular Dysfunction; Ventricular Remodeling

Abstract B-natriuretic peptide (BNP) is a 32-amino acid polypeptide secreted from the cardiac ventricles in response to ventricular volume expansion and pressure overload. BNP levels are elevated in patients with symptomatic left ventricular dysfunction, and levels correlate with severity of symptoms and with prognosis. Numerous studies indicate that BNP may considerably improve the management of patients with heart failure and may become a routine serum parameter in clinical medicine. In this review, the utility of BNP in different clinical settings will be discussed.

Topics: Aged; Biomarkers; Death, Sudden, Cardiac; Diagnosis, Differential; Dyspnea; Emergencies; Female; Heart Failure; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Pilot Projects; Predictive Value of Tests; Prognosis; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Reference Values; Retrospective Studies; Risk Assessment; Sensitivity and Specificity; Ventricular Dysfunction, Left

1. The role of vasoactive peptide systems in the pulmonary vasculature has been studied much less extensively than systemic vascular and endocrine effects. The current understanding of the role of the renin-angiotensin (RAS) and natriuretic peptide systems (NPS) in the pulmonary circulation is therefore reviewed. 2. Plasma concentrations of angiotensin II, the main vasoactive component of the RAS, are elevated in pulmonary hypertension and may interact with hypoxaemia to cause further pulmonary vasoconstriction. Pharmacological manipulation of angiotensin II can attenuate hypoxic pulmonary vasoconstriction but larger studies are needed to establish the efficacy of this therapeutic strategy in established pulmonary hypertension. 3. Although all the known natriuretic peptides, ANP, BNP and CNP are elevated in cor pulmonale, only ANP and BNP appear to have pulmonary vasorelaxant activity in humans. ANP and BNP can also attenuate hypoxic pulmonary vasoconstriction, suggesting a possible counter-regulatory role for these peptides. Inhibition of ANP/BNP metabolism by neutral endopeptidase has been shown to attenuate development of hypoxic pulmonary hypertension but this property has not been tested in humans. 4. It is also well established that there are potentially important endocrine and systemic circulatory interactions between the RAS and NPS. This also occurs in the pulmonary circulation and in humans, where at least BNP acts to attenuate angiotensin II induced pulmonary vasoconstriction. This interaction may be particularly relevant as a mechanism to counter-regulate overactivity of the RAS.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Humans; Hypertension, Pulmonary; Hypoxia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pulmonary Circulation; Renin-Angiotensin System; Vascular Resistance; Vasoconstriction

Long-term benefits of pulmonary artery denervation (PADN) for patients with combined precapillary and postcapillary pulmonary hypertension (CpcPH) secondary to left heart failure are unknown.. The authors sought to report the 3-year clinical results of PADN for patients with CpcPH.. A total of 98 patients with CpcPH, defined as having mean pulmonary arterial pressure of ≥25 mm Hg, pulmonary capillary wedge pressure of >15 mm Hg, and pulmonary vascular resistance of >3.0 WU, were randomly assigned to receive the sham + sildenafil or PADN. The primary endpoint was the occurrence of clinical worsening defined as cardiopulmonary death, rehospitalization or heart/lung transplantation at 3-year follow-up. Changes in the 6-minute walk distance and N-terminal pro-B-type natriuretic peptide served as secondary points.. At the 3-year follow-up, clinical worsening was reported in 49 (50.0%) patients, with 31 (62.0%) in the sham + sildenafil group and 18 (37.5%) in the PADN group (HR: 2.13 [95% CI: 1.19-3.81]; P = 0.011), largely driven by a higher rate of rehospitalization in the sham + sildenafil group (56.2% vs 35.4%; HR: 1.96 [95% CI: 1.07-3.58]; P = 0.029) by Cox proportional hazards regression. At the end of the study, cardiopulmonary-related deaths occurred in 16 (32.0%) patients in the sham and 9 (18.8%) (P = 0.167) patients in the PADN group. PADN also resulted in a more profound increase in the 6-minute walk distance and reduction in N-terminal pro-B-type natriuretic peptide.. PADN is associated with significant improvements in exercise capacity, cardiac function, and clinical outcomes. Further study without approved drugs for pulmonary arterial hypertension is required to confirm the benefits of PADN for patients with CpcPH. (Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure [PADN-5]; NCT02220335).

Topics: Heart Failure; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Pulmonary Artery; Sildenafil Citrate

Understanding of the pathophysiologic manifestations of pulmonary arterial hypertension (PAH) is still evolving. The aims of the present study were to determine the alterations in blood rheology, and to investigate the relationship between those alterations and laboratory parameters in PAH.. The study included 21 consecutive treatment-naive patients with PAH and 32 age and sex-matched healthy controls. Patients were categorised in class II (n=6), class III (n=13), and class IV (n=2). All subjects underwent right-heart catheterisation. Erythrocyte deformability and aggregation were measured by an ektacytometer.. The increase in erythrocyte aggregation and the decrease in deformability may theoretically increase the flow resistance and may be of haemodynamic significance. The association between erythrocyte aggregation and NT pro-BNP may indicate that erythrocyte aggregation increases with disease progression. These alterations contribute to the understanding of the pathophysiology and could serve as markers of disease presence.

Topics: Aged; Biomarkers; Cardiac Catheterization; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Vascular Resistance

Eisenmenger syndrome describes congenital heart disease-associated severe pulmonary hypertension accompanied by right-to-left shunting. The multicenter, double-blind, randomized, placebo-controlled, 16-week, phase III MAESTRO study (Macitentan in Eisenmenger Syndrome to Restore Exercise Capacity) evaluated the efficacy and safety of the endothelin receptor antagonist macitentan in patients with Eisenmenger syndrome.. Patients with Eisenmenger syndrome aged ≥12 years and in World Health Organization functional class II-III were randomized 1:1 to placebo or macitentan 10 mg once daily for 16 weeks. Patients with complex cardiac defects, Down syndrome and background PAH therapy were eligible. The primary end point was change from baseline to week 16 in 6-minute walk distance. Secondary end points included change from baseline to week 16 in World Health Organization functional class. Exploratory end points included NT-proBNP (N-terminal pro-B-type natriuretic peptide) at end of treatment expressed as a percentage of baseline. In a hemodynamic substudy, exploratory end points included pulmonary vascular resistance index (PVRi) at week 16 as a percentage of baseline.. Two hundred twenty six patients (macitentan n=114; placebo n=112) were randomized. At baseline, 60% of patients were in World Health Organization functional class II and 27% were receiving phosphodiesterase type-5 inhibitors. At week 16, the mean change from baseline in 6-minute walk distance was 18.3 m and 19.7 m in the macitentan and placebo groups (least-squares mean difference, -4.7 m; 95% confidence limit (CL), -22.8, 13.5; P=0.612). World Health Organization functional class improved from baseline to week 16 in 8.8% and 14.3% of patients in the macitentan and placebo groups (odds ratio, 0.53; 95% CL, 0.23, 1.24). NT-proBNP levels decreased with macitentan versus placebo (ratio of geometric means, 0.80; 95% CL, 0.68, 0.94). In the hemodynamic substudy (n=39 patients), macitentan decreased PVRi compared with placebo (ratio of geometric means, 0.87; 95% CL, 0.73, 1.03). The most common adverse events with macitentan versus placebo were headache (11.4 versus 4.5%) and upper respiratory tract infection (9.6 versus 6.3%); a hemoglobin decrease from baseline of ≥2 g/dL occurred in 36.0% versus 8.9% of patients. Five patients (3 macitentan; 2 placebo) prematurely discontinued treatment and 1 patient died (macitentan group).. Macitentan did not show superiority over placebo on the primary end point of change from baseline to week 16 in exercise capacity in patients with Eisenmenger syndrome.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT01743001.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Biomarkers; Child; Double-Blind Method; Down Syndrome; Eisenmenger Complex; Endothelin Receptor Antagonists; Exercise Tolerance; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Pyrimidines; Recovery of Function; Sulfonamides; Time Factors; Treatment Outcome; Walk Test; Young Adult

Pulmonary hypertension (PH) is extremely common in acute decompensated heart failure (ADHF) patients and predicts increased mortality. Obstructive sleep apnea (OSA), highly prevalent in congestive heart failure patients, may contribute to further elevated pulmonary pressures. This study evaluates the impact of positive airway pressure (PAP) therapy on PH in patients admitted for ADHF with OSA.. A two-center randomized control trial comparing standard of care (SOC) therapy for ADHF versus addition of PAP therapy in patients with concomitant OSA.. Twenty-one consecutive patients were enrolled with 1:1 randomization to SOC versus SOC plus 48-hour PAP therapy protocol. In the intervention arm, the mean pulmonary artery systolic pressure (PASP) difference before therapy and after 48 hours of PAP therapy was -15.8 ± 3.2 (58.6 ± 2.5 mm Hg to 42.8 ± 2.7) versus the SOC arm where the mean PASP difference was -5.2 ± 2.6 (62.7 ± 3.3 mm Hg reduced to 57.5 ± 3.9) (p = 0.025). In addition, ejection fraction in the intervention arm improved (3.4 ± 1.5% versus -0.5 ± 0.5 %) (p = 0.01). Significant improvement was also noted in tricuspid annular plane systolic excursion (TAPSE) and right ventricular systolic area in the intervention arm but not in NT-pro-BNP or 6-minute walk distance.. In patients with ADHF and OSA, addition of 48 hours of PAP therapy to SOC treatment significantly reduced PH. In addition, PAP therapy was able to improve right and left ventricular function. ClinicalTrials.gov identifier: NCT02963597.

Topics: Aged; Aged, 80 and over; Continuous Positive Airway Pressure; Female; Heart Failure; Heart Ventricles; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Sleep Apnea, Obstructive; Ventricular Function, Left

The MELODY-1 study evaluated macitentan for pulmonary hypertension because of left heart disease (PH-LHD) in patients with combined post- and pre-capillary PH.63 patients with PH-LHD and diastolic pressure gradient ≥7 mmHg and pulmonary vascular resistance (PVR) >3WU were randomised to macitentan 10 mg (n=31) or placebo (n=32) for 12 weeks. The main end-point assessed a composite of significant fluid retention (weight gain ≥5% or ≥5 kg because of fluid overload or parenteral diuretic administration) or worsening in New York Heart Association functional class from baseline to end of treatment. Exploratory end-points included changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and haemodynamics at week 12.Seven macitentan-treated and four placebo-treated patients experienced significant fluid retention/worsening functional class; treatment difference, 10.08% (95% CI -15.07-33.26; p=0.34). The difference, driven by the fluid retention component, was apparent within the first month. At week 12,

Topics: Aged; Blood Pressure; Double-Blind Method; Female; Humans; Hypertension, Pulmonary; Internationality; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Wedge Pressure; Pyrimidines; Sulfonamides; Treatment Outcome; Vascular Resistance; Ventricular Dysfunction, Left; Walk Test

The correlation between serum adiponectin concentration and hemodynamics or certain metabolic markers in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is unknown.Methods and Results:We enrolled 30 CTEPH patients who underwent interventional therapy of balloon pulmonary angioplasty or pulmonary endarterectomy. Serum adiponectin concentrations positively correlated with B-type natriuretic peptide (BNP) concentrations, pulmonary vascular resistance, and mean pulmonary arterial pressure. After the therapeutic interventions, serum adiponectin concentrations improved and changes in serum adiponectin concentrations significantly correlated with changes in BNP concentrations.. Adiponectin can be a useful marker for the severity of CTEPH.

Topics: Adiponectin; Aged; Angioplasty, Balloon; Biomarkers; Chronic Disease; Endarterectomy; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Severity of Illness Index

The effect of macitentan on haemodynamic parameters and NT-proBNP levels was evaluated in pulmonary arterial hypertension (PAH) patients in the SERAPHIN study. Association between these parameters and disease progression, assessed by the primary endpoint (time to first morbidity/mortality event), was explored.. Of the 742 randomized patients, 187 with right heart catheterization at baseline and month 6 participated in a haemodynamic sub-study. Prespecified endpoints included change from baseline to month 6 in cardiac index (CI), right atrial pressure (RAP), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), mixed-venous oxygen saturation, and NT-proBNP. Exploratory analyses examined associations between CI, RAP, and NT-proBNP and disease progression using the Kaplan-Meier method and Cox regression models. Macitentan improved CI, RAP, mPAP, PVR and NT-proBNP vs. placebo at month 6. Absolute levels of CI, RAP and NT-proBNP at baseline and month 6, but not their changes, were associated with morbidity/mortality events. Patients with CI > 2.5 L/min/m2, RAP < 8 mmHg, or NT-proBNP < 750 fmol/ml at month 6 had a lower risk of morbidity/mortality than those not meeting these thresholds (HR 0.49, 95% CL 0.28-0.86; HR 0.72, 95% CL 0.42-1.22; and HR 0.22, 95% CL 0.15-0.33, respectively).. For all treatment groups, baseline and month 6 values of CI, RAP, and NT-proBNP, but not their changes, were associated with morbidity/mortality events, confirming their relevance in predicting disease progression in patients with PAH. By improving those parameters, macitentan increased the likelihood of reaching threshold values associated with lower risk of morbidity/mortality.

Topics: Cardiac Catheterization; Disease Progression; Dose-Response Relationship, Drug; Endothelin Receptor Antagonists; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pyrimidines; Risk Factors; Sulfonamides; Treatment Outcome; Ventricular Dysfunction, Right

Selexipag (Uptravi) is an oral selective IP prostacyclin receptor agonist approved for the treatment of pulmonary arterial hypertension (PAH). The pivotal GRIPHON study was the largest clinical study ever conducted in PAH patients, providing long-term data from 1,156 patients. PAH comedication did not affect exposure to selexipag, while exposure to its active metabolite ACT-333679 was reduced by 30% when taken in combination, clinically not relevant in the context of individual dose up-titration. Using log-linear regression models linking model-predicted steady-state exposure to pharmacodynamics (PD), exposure to selexipag and ACT-333679 showed some statistically significant, albeit not clinically relevant, effects on exercise capacity, laboratory values, and the occurrence of prostacyclin-related adverse events, but not on vital signs or adverse events denoting hemorrhage. Using suitable modeling techniques, the GRIPHON study yielded clinically relevant data with limited burden of pharmacokinetics (PK) blood sampling, demonstrating that PK/PD modeling enables firm conclusions even with sparse PK and PD sampling.

Topics: Acetamides; Acetates; Adult; Antihypertensive Agents; Bilirubin; Double-Blind Method; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Leukocyte Count; Male; Models, Biological; Natriuretic Peptide, Brain; Peptide Fragments; Pyrazines; Treatment Outcome

Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar.. Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 73·0% of baseline in the macitentan group and to 87·2% in the placebo group (geometric means ratio 0·84, 95% CI 0·70-0·99, p=0·041). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]).. In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated.. Actelion Pharmaceuticals Ltd.

Topics: Aged; Chronic Disease; Double-Blind Method; Endothelin Receptor Antagonists; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Pyrimidines; Sulfonamides; Treatment Outcome; Vascular Resistance

We recently showed that sildenafil did not improve pulmonary pressures and exercise capacity in a cohort of patients with heart failure and preserved ejection fraction (HFpEF) and predominantly postcapillary pulmonary hypertension. Here, we present the effects of sildenafil on cardiac structure and function, cardiopulmonary exercise testing, laboratory parameters and health-related quality of life measures.. Fifty-two HFpEF patients with pulmonary hypertension (mean pulmonary artery pressure >25 mmHg; pulmonary artery wedge pressure >15 mmHg) were randomized to sildenafil 60 mg three times a day or placebo and treated for 12 weeks. Sildenafil neither changed cardiac structure nor function on echocardiography compared with placebo. Considering all patients irrespective of maximal effort, sildenafil reduced peak heart rate by 8 b.p.m. [95% confidence interval (CI) -14.97 to -1.03] and peak blood pressure by 13.8 mmHg (95% CI -22.04 to -5.47)/7.3 mmHg (95% CI -13.60 to -1.07) (both P < 0.05 vs. placebo). The minute ventilation/carbon dioxide production (VE/VCO. Treatment with sildenafil for 12 weeks in patients with HFpEF and predominantly isolated postcapillary pulmonary hypertension did not affect cardiac structure and function, integrative exercise responses, laboratory parameters, and/or quality of life. Clinicaltrials.gov number NCT01726049.

Topics: Aged; Aged, 80 and over; Blood Pressure; Cardiac Catheterization; Echocardiography; Exercise Test; Female; Glycated Hemoglobin; Health Status; Heart Failure; Heart Rate; Hemoglobins; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Pulmonary Wedge Pressure; Quality of Life; Sildenafil Citrate; Stroke Volume; Treatment Outcome

Patients with pulmonary arterial hypertension (PAH) who do not have an adequate response to therapy with phosphodiesterase-5 inhibitors (PDE-5i) may have insufficient synthesis of cyclic guanosine monophosphate (cGMP). These patients may respond to a direct soluble guanylate cyclase (sGC) stimulator such as riociguat. RESPITE (NCT02007629) was an open-label, multicenter, uncontrolled, single-arm phase 3b study of riociguat in patients with PAH who demonstrated an insufficient response to treatment with PDE-5i. Insufficient response was defined as World Health Organization functional class (WHO FC) III despite PDE-5i therapy for at least 90 days; 6-min walk distance (6MWD) of 165-440 m, and right-heart catheterization showing mean pulmonary artery pressure >30 mmHg, cardiac index <3.0 L/min/m

Topics: Adolescent; Adult; Aged; Endothelin Receptor Antagonists; Enzyme Activators; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide; Outcome Assessment, Health Care; Phosphodiesterase 5 Inhibitors; Pyrazoles; Pyrimidines; Quality of Life; Sildenafil Citrate; Soluble Guanylyl Cyclase; Young Adult

In a previous study, 6-minute walk distance (6MWD) improvement with sildenafil was not dose dependent at the 3 doses tested (20, 40, and 80 mg 3 times daily [TID]). This study assessed whether lower doses were less effective than the approved 20-mg TID dosage.. Treatment-naive patients with pulmonary arterial hypertension were randomized to 12 weeks of double-blind sildenafil 1, 5, or 20 mg TID; 12 weeks of open-label sildenafil 20 mg TID followed. Changes from baseline in 6-minute walk distance (6MWD) for sildenafil 1 or 5 mg versus 20 mg TID were compared using a Williams test. Hemodynamics, functional class, and biomarkers were assessed.. The study was prematurely terminated for non-safety reasons, with 129 of 219 planned patients treated. At week 12, 6MWD change from baseline was significantly greater for sildenafil 20 versus 1 mg (P = 0.011) but not versus 5 mg. At week 24, 6MWD increases from baseline were larger in those initially randomized to 20 versus 5 or 1 mg (74 vs 50 and 47 m, respectively). At week 12, changes in hemodynamic parameters were generally small and variable between treatment groups; odds ratios for improvement in functional class were not statistically significantly different. Improvements in B-type natriuretic peptide levels were significantly greater with sildenafil 20 versus 1 but not 5 mg.. Sildenafil 20 mg TID appeared to be more effective than 1 mg TID for improving 6MWD; sildenafil 5 mg TID appeared to have similar clinical and hemodynamic effects as 20 mg TID.. ClinicalTrials.gov NCT00430716 (Registration date: January 31, 2007).

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Echocardiography; Female; Hemodynamics; Humans; Hypertension, Pulmonary; International Cooperation; Male; Middle Aged; Natriuretic Peptide, Brain; Severity of Illness Index; Sildenafil Citrate; Treatment Outcome; Vasodilator Agents; Walk Test; Young Adult

Galectin-3, a novel binding-lectin involved in inflammation and fibrosis, is elevated in heart failure and is independently predictive of mortality in this condition. We sought to evaluate galectin-3 levels and its prognostic value in patients with pulmonary hypertension (PH), a known inflammatory state, in the setting of pulmonary arterial hypertension (PAH) and in heart failure with preserved ejection fraction-associated PH (HFpEF-PH).. We measured galectin-3 levels in 76 patients with PH; 37 patients with PAH and 39 patients with HFpEF-PH. Baseline characteristics, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels were assessed. Univariate and multivariate analyses were used to assess the prognostic value of galectin-3.. Median (IQR) galectin-3 (ng/mL) for the entire cohort was 24.65 (IQR=10.39, 32.90); 22.33 (IQR=18.94, 27.30) and 28.94 (IQR=21.67, 39.85) in the PAH and HFpEF-PH, respectively (p=0.07). After evaluation of the galectin-3 levels by tertile, mortality rates were 16% (4/25), 34.6% (9/26), and 48% (12/25) in tertiles 1-3, respectively, and Kaplan-Meier analysis revealed a significant increase in mortality across increasing galectin-3 tertiles (log-rank p=0.014). On Cox regression analysis, galectin-3 was a strong predictor of mortality on both univariate HR=2.09 per tertile (95% CI=1.21, 3.62 per tertile; p-trend=0.008) and multivariate analysis HR=2.19 per tertile (95% CI=1.06, 4.54; p-trend=0.035) after adjusting for age, sex, race, glomerular filtration rate (eGFR), NT-proBNP, medications, and aetiology of PH (PAH vs. HFpEF-PH).. Galectin-3 is a strong, independent prognostic marker in PH, regardless of aetiology. Larger studies should further evaluate the role of galectin-3 as a prognostic biomarker and possible therapeutic target in PH.

Topics: Aged; Blood Proteins; Disease-Free Survival; Female; Galectin 3; Galectins; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Survival Rate

The impact of exercise training on the right heart and pulmonary circulation has not yet been invasively assessed in patients with pulmonary hypertension (PH) and right heart failure. This prospective randomized controlled study investigates the effects of exercise training on peak VO2/kg, haemodynamics, and further clinically relevant parameters in PH patients.. Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thrombo-embolic PH (54% female, 56 ± 15 years, 84% World Health Organization functional class III/IV, 53% combination therapy) on stable disease-targeted medication were randomly assigned to a control and training group. Medication remained unchanged during the study period. Non-invasive assessments and right heart catheterization at rest and during exercise were performed at baseline and after 15 weeks. Primary endpoint was the change in peak VO2/kg. Secondary endpoints included changes in haemodynamics. For missing data, multiple imputation and responder analyses were performed. The study results showed a significant improvement of peak VO2/kg in the training group (difference from baseline to 15 weeks: training +3.1 ± 2.7 mL/min/kg equals +24.3% vs. control -0.2 ± 2.3 mL/min/kg equals +0.9%, P < 0.001). Cardiac index (CI) at rest and during exercise, mean pulmonary arterial pressure, pulmonary vascular resistance, 6 min walking distance, quality of life, and exercise capacity significantly improved by exercise training.. Low-dose exercise training at 4-7 days/week significantly improved peak VO2/kg, haemodynamics, and further clinically relevant parameters. The improvements of CI at rest and during exercise indicate that exercise training may improve the right ventricular function. Further, large multicentre trials are necessary to confirm these results.

Topics: Analysis of Variance; Biomarkers; Cardiac Output; Chronic Disease; Exercise Test; Exercise Therapy; Exercise Tolerance; Female; Heart Rate; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Prospective Studies; Pulmonary Wedge Pressure; Thromboembolism; Treatment Outcome; Vascular Resistance; Ventricular Dysfunction, Right

Pulmonary arterial hypertension (PAH) is a rare progressive disease of the pulmonary vasculature that is characterized by endothelial dysfunction, inflammation, and right ventricular dysfunction.. The main objective was to determine whether endothelial, inflammatory, and cardiac biomarkers would be associated with the World Health Organization functional assessment and survival in patients with PAH.. We performed a retrospective cohort study of patients with PAH enrolled in the Randomized Clinical Trial of Aspirin and Simvastatin for Pulmonary Arterial Hypertension (ASA-STAT). Biomarkers (N-terminal fragment of pro-BNP [NT-pro-BNP], von Willebrand factor [vWF], soluble P selectin, C-reactive protein, total and high-density lipoprotein cholesterol, triglycerides, tumor necrosis factor, IL-6, β-thromboglobulin, and thromboxane B2) were measured at baseline. Patients from the study were followed until lung transplantation, death, or August 1, 2013. Ordinal logistic regression and Cox regression analyses were performed.. Sixty-five patients with PAH were enrolled. The mean age was 51 years, and 86% were women. Higher vWF activity, lower high-density lipoprotein cholesterol, and higher thromboxane B2 levels were associated with worse World Health Organization functional class after adjustment for age, sex, and etiology of PAH. Higher NT-pro-BNP levels, lower vWF activity, and lower total cholesterol were associated with an increased risk of death or lung transplant after adjustment for age, sex, etiology of PAH, and 6-minute-walk distance.. In patients with PAH, lower vWF activity and cholesterol levels and higher NT-pro-BNP levels at baseline were associated with an increased risk of death or transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT00384865).

Topics: Adult; beta-Thromboglobulin; Biomarkers; C-Reactive Protein; Cholesterol, HDL; Exercise Test; Female; Humans; Hypertension, Pulmonary; Interleukin-6; Lung Transplantation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Respiratory Function Tests; Retrospective Studies; Risk Factors; Survival Analysis; von Willebrand Factor

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, debilitating, and life-threatening disease. We investigated associations between markers of disease severity and long-term outcomes in patients with inoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy (PEA) who were receiving the soluble guanylate cyclase stimulator riociguat. We also present safety and efficacy from the final data cutoff of CHEST-2, where most patients had received riociguat for at least 2 years.. Eligible patients from the CHEST-1 study entered the CHEST-2 open-label extension study, in which all patients received riociguat individually adjusted to a maximum dose of 2·5 mg three times per day. The primary endpoint was safety and tolerability. We did exploratory assessments of associations between markers of disease severity (6-min walking distance [6MWD], N-terminal prohormone of brain natriuretic peptide [NT-proBNP] concentration, and WHO functional class) at baseline and follow-up with overall survival and clinical worsening-free survival. We used Kaplan-Meier and Cox proportional hazards analyses. CHEST-2 is registered at ClinicalTrials.gov, number NCT00910429.. 237 patients entered CHEST-2. At 2 years, overall survival was 93% (95% CI 89-96) and clinical worsening-free survival was 82% (77-87). A significant association with overall survival was seen for 6MWD and NT-proBNP concentration at baseline (p=0·0199 and p=0·0183, respectively) and at follow-up (p=0·0385 and p=0·0068, respectively). Change from baseline in 6MWD was also significantly associated with survival (p=0·0047). WHO functional class at baseline and follow-up showed no significant association with overall survival but was associated with clinical worsening-free survival. Riociguat was well tolerated by most patients and no new safety signals were identified. Serious adverse events were seen in 129 (54%) of 237 patients, and 14 (6%) discontinued riociguat therapy because of adverse events.. Riociguat may be used long term in patients with CTEPH. 6MWD and NT-proBNP concentration are good prognostic markers.. Bayer Pharma AG.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Chronic Disease; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Embolism; Pyrazoles; Pyrimidines; Time; Treatment Outcome; Young Adult

Pulmonary arterial hypertension is a chronic disease associated with poor long-term outcomes. Identifying predictors of long-term outcome in pulmonary arterial hypertension is important to assess disease severity and guide treatment. We investigate associations between efficacy parameters and long-term outcomes in patients with pulmonary arterial hypertension receiving riociguat in the PATENT-2 study. We also present safety and efficacy data from the final data cutoff of PATENT-2, where most patients had received at least 2 years of riociguat treatment.. Eligible patients from the PATENT-1 study entered the PATENT-2 open-label extension, which will continue until all patients transition to the commercial drug. All patients received riociguat individually adjusted to a maximum dose of 2·5 mg three times a day. The primary endpoint was safety and tolerability, assessed with recording adverse events, serious adverse events, discontinuations, and deaths; exploratory assessments included 6-min walking distance (6MWD), WHO functional class, N-terminal prohormone of brain natriuretic peptide (NT-proBNP)concentrations, Borg dyspnoea score, health-related quality of life (EQ-5D score), survival, and clinical worsening-free survival. Association between efficacy parameters and long-term outcomes was assessed using Kaplan-Meier analyses and a Cox proportional-hazards regression model. PATENT-2 is registered at ClinicalTrials.gov, number NCT00863681.. 396 patients entered PATENT-2, of whom 197 patients were receiving riociguat monotherapy and 199 were receiving riociguat in combination with endothelin receptor antagonists or prostanoids, or both. A significant association was noted between 6MWD, NT-proBNP concentration, and WHO functional class and overall survival at baseline (p=0·0006, 0·0225, and 0·0191, respectively), and at follow-up (p=0·021, 0·0056, and 0·0048, respectively). Riociguat was well tolerated in PATENT-2. Serious adverse events were recorded in 238 (60%) of the total population, and 45 (11%) patients discontinued treatment because of an adverse event. Improvements in 6MWD, WHO functional class, and NT-proBNP concentrations were maintained after 2 years of treatment.. These results support the long-term use of riociguat in patients with pulmonary arterial hypertension, and emphasise the prognostic value of 6MWD, WHO functional class, and NT-proBNP concentrations.. Bayer Pharma AG.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Endothelin Receptor Antagonists; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prostaglandins; Pulmonary Artery; Pyrazoles; Pyrimidines; Quality of Life; Time; Treatment Outcome; Young Adult

Biomarkers may be helpful in prediction of outcomes of infants with congenital diaphragmatic hernia. The predictive value of high-sensitivity troponin T and N-terminal pro-brain natriuretic peptide was investigated in 128 infants with congenital diaphragmatic hernia. After correction for multiple testing, those biomarkers did not predict severe pulmonary hypertension, death, need of extracorporeal membrane oxygenation, or bronchopulmonary dysplasia.. Netherlands Trial Registry: 1310.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Extracorporeal Membrane Oxygenation; Female; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Infant, Newborn; Male; Natriuretic Peptide, Brain; Netherlands; Prognosis; Prospective Studies; Severity of Illness Index; Troponin T

Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce.. In this event-driven, double-blind study, we randomly assigned, in a 2:1:1 ratio, participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of ambrisentan plus placebo (ambrisentan-monotherapy group), or 40 mg of tadalafil plus placebo (tadalafil-monotherapy group), all administered once daily. The primary end point in a time-to-event analysis was the first event of clinical failure, which was defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression, or unsatisfactory long-term clinical response.. The primary analysis included 500 participants; 253 were assigned to the combination-therapy group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil-monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the participants in these groups, respectively, and in 31% of the pooled-monotherapy group (the two monotherapy groups combined). The hazard ratio for the primary end point in the combination-therapy group versus the pooled-monotherapy group was 0.50 (95% confidence interval [CI], 0.35 to 0.72; P<0.001). At week 24, the combination-therapy group had greater reductions from baseline in N-terminal pro-brain natriuretic peptide levels than did the pooled-monotherapy group (mean change, -67.2% vs. -50.4%; P<0.001), as well as a higher percentage of patients with a satisfactory clinical response (39% vs. 29%; odds ratio, 1.56 [95% CI, 1.05 to 2.32]; P=0.03) and a greater improvement in the 6-minute walk distance (median change from baseline, 48.98 m vs. 23.80 m; P<0.001). The adverse events that occurred more frequently in the combination-therapy group than in either monotherapy group included peripheral edema, headache, nasal congestion, and anemia.. Among participants with pulmonary arterial hypertension who had not received previous treatment, initial combination therapy with ambrisentan and tadalafil resulted in a significantly lower risk of clinical-failure events than the risk with ambrisentan or tadalafil monotherapy. (Funded by Gilead Sciences and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.).

Topics: Adult; Aged; Carbolines; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Hospitalization; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Phenylpropionates; Pyridazines; Risk Factors; Tadalafil

To compare the therapeutic efficacy of recombinant human brain natriuretic peptide and prostaglandin E1 in the treatment of pulmonary hypertension after mitral valve replacement.. Sixty patients with postoperative pulmonary hypertension were divided randomly into 3 groups that received saline, prostaglandin E1, and natriuretic peptide infusions for 12 hours each. The hemodynamics data were monitored consecutively, and the levels of thromboxane A2 and cyclic guanosine monophosphate were detected pretreatment, after treatment, and 1 week after surgery.. The arterial pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure decreased 1 hour after prostaglandin E1 treatment and rebounded after treatment discontinuation. The pulmonary arterial pressure and pulmonary capillary wedge pressure in the natriuretic peptide group decreased 3 hours after treatment; pulmonary arterial pressure decreased less than that of the prostaglandin group, and there was no evidence of hemodynamic rebound after treatment discontinuation. The natriuretic peptide had no significant effects on arterial pressure. In both the prostaglandin and natriuretic peptide groups, cyclic guanosine monophosphate increased after the treatment, which was even higher in the latter group. Prostaglandin E1 could lead to the decrease of thromboxane A2, which was not seen in the natriuretic peptide group.. Both brain natriuretic peptide and prostaglandin E1 can effectively reduce pulmonary hypertension; however, natriuretic peptide has a slower and milder efficacy. The effects of these 2 drugs in reducing the pulmonary arterial pressure may be mediated through different pathways.

Topics: Alprostadil; Cyclic GMP; Double-Blind Method; Female; Heart Valve Prosthesis Implantation; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mitral Valve; Natriuretic Agents; Natriuretic Peptide, Brain; Thromboxane A2; Vasodilator Agents

Some potential biomarkers have been reported recently in patients with pulmonary arterial hypertension (PAH), but the most clinically useful among these potential biomarkers, especially in childhood PAH, has not been identified. Therefore, this study investigated which biomarker is useful in assessing severity of and patient prognosis in childhood idiopathic PAH (IPAH)/heritable PAH (HPAH).. Fifty-nine patients who were younger than 16 years at onset of IPAH/HPAH were selected. The following 10 biomarker candidates were quantified: high-sensitivity troponin T, human heart fatty acid-binding protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), pentraxin-3, soluble ST2 (sST2), angiopoietin-2 (Ang-2), matrix metalloproteinase 2, tenascin C, endostatin (ES), and thymidine kinase. Functional characteristics and clinical outcomes were analyzed retrospectively. NT-proBNP, sST2, Ang-2, and ES correlated well with New York Heart Association class. On area under the receiver operating characteristic curve analysis, sST2 had a significantly good relationship with prognosis. On Kaplan-Meier curve and univariate Cox regression analyses, elevated sST2 and NT-proBNP level predicted poor outcome of the present patients with childhood IPAH/HPAH. Furthermore, patients with elevated sST2 had significantly worse prognosis among those with high NT-proBNP.. The sST2 and NT-proBNP combination is a useful biomarker to predict clinical condition and outcome in patients with childhood IPAH/HPAH.  

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Female; Humans; Hypertension, Pulmonary; Interleukin-1 Receptor-Like 1 Protein; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Receptors, Cell Surface

The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial.. We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥ 3.0 m/s cuttof, which has a 67-75% positive predictive value for mean pulmonary artery pressure ≥ 25 mm Hg was used. Among 572 subjects, 11.2% had TRV ≥ 3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥ 160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV ≥ 3.0 m/sec. At 24 months the cumulative survival was 83% with TRV ≥ 3.0 m/sec and 98% with TRV < 3.0 m/sec (p < 0.0001). The hazard ratios for death were 11.1 (95% CI 4.1-30.1; p < 0.0001) for TRV ≥ 3.0 m/sec, 4.6 (1.8-11.3; p = 0.001) for NT-proBNP ≥ 160 pg/mL, and 14.9 (5.5-39.9; p < 0.0001) for both TRV ≥ 3.0 m/sec and NT-proBNP ≥ 160 pg/mL. Age > 47 years, male gender, chronic transfusions, WHO class III-IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death.. A TRV ≥ 3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable. The study is registered in ClinicalTrials.gov with identifier: NCT00492531.

Topics: Adult; Anemia, Sickle Cell; Blood Flow Velocity; Blood Pressure; Cohort Studies; Creatinine; Female; Ferritins; Follow-Up Studies; Hemolysis; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Risk Factors; Severity of Illness Index; United Kingdom; United States; Walking

In translational models of pulmonary arterial hypertension (PAH), spironolactone improves cardiopulmonary hemodynamics by attenuating the adverse effects of hyperaldosteronism on endothelin type-B receptor function in pulmonary endothelial cells. This observation suggests that coupling spironolactone with inhibition of endothelin type-A receptor-mediated pulmonary vasoconstriction may be a useful treatment strategy for patients with PAH. We examined clinical data from patients randomized to placebo or the selective endothelin type-A receptor antagonist ambrisentan (10 mg/day) and in whom spironolactone use was reported during ARIES-1 and -2, which were randomized, double-blind, placebo-controlled trials assessing the effect of ambrisentan for 12 weeks on clinical outcome in PAH. From patients randomized to placebo (n = 132) or ambrisentan (n = 67), we identified concurrent spironolactone use in 21 (15.9%) and 10 (14.9%) patients, respectively. Compared with patients treated with ambrisentan alone (n = 57), therapy with ambrisentan + spironolactone improved change in 6-minute walk distance by 94% at week 12 (mean ± SE, +38.2 ± 8.1 vs +74.2 ± 27.4 m, p = 0.11), improved plasma B-type natriuretic peptide concentration by 1.7-fold (p = 0.08), and resulted in a 90% relative increase in the number of patients improving ≥1 World Health Organization functional class (p = 0.08). Progressive illness, PAH-associated hospitalizations, or death occurred as an end point for 5.3% of ambrisentan-treated patients; however, no patient treated with ambrisentan + spironolactone reached any of these end points. In conclusion, these pilot data suggest that coupling spironolactone and endothelin type-A receptor antagonism may be clinically beneficial in PAH. Prospective clinical trials are required to further characterize our findings.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Diuretics; Double-Blind Method; Drug Therapy, Combination; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Phenylpropionates; Pilot Projects; Pyridazines; Severity of Illness Index; Spironolactone; Treatment Outcome; Young Adult

To examine the effect of balloon pulmonary angioplasty (BPA) on chronic thromboembolic pulmonary hypertension (CTEPH) in patients with inoperable disease or persistent pulmonary hypertension after pulmonary endarterectomy.. Observational cohort study.. Referred patients with inoperable or persistent CTEPH.. Twenty consecutive CTEPH patients (10 females), aged 60±10 years.. Right heart catheterisation, functional capacity (cardiopulmonary exercise testing (CPET) and NYHA class) and blood sampled biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T examined at the time of diagnosis and repeated in all patients 3 months after the last BPA.. Seventy-three catheterisations were performed with 18.6±6.1 BPAs per patient on segmental and subsegmental arteries. Two deaths occurred following the first BPA, with an overall 10% periprocedural death rate. Reperfusion oedema complicated seven procedures. Comparisons before and after BPA showed significant haemodynamic improvements, including decreased mean pulmonary artery pressure (mPAP) (45±11 mm Hg vs 33±10 mm Hg; p<0.001) and increased cardiac output (4.9±1.6 L/min vs 5.4±1.9 L/min; p=0.011). Reduced right ventricular strain was indicated by significantly lower plasma levels of NT-proBNP and troponin T. Significant improvement in functional capacity was evident as assessed by NYHA class (3.0±0.5 vs 2.0±0.5; p<0.001) and CPET (13.6±5.6 mL/kg/min vs 17.0±6.5 mL/kg/min; p<0.001). Seventeen patients (85%) were alive after 51±30 months of follow-up.. BPA may offer an alternative form of treatment in selected CTEPH patients. While prognostic markers such as haemodynamics, functional capacity and biomarkers improve, significant periprocedural complications must be recognised. Randomised trials are warranted.

Topics: Aged; Angioplasty, Balloon; Arterial Pressure; Biomarkers; Cardiac Catheterization; Cardiac Output; Chronic Disease; Endarterectomy; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Norway; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Pulmonary Embolism; Recovery of Function; Time Factors; Treatment Outcome; Troponin T; Ventricular Function, Right

Riociguat, a soluble guanylate cyclase stimulator, has been shown in a phase 2 trial to be beneficial in the treatment of pulmonary arterial hypertension.. In this phase 3, double-blind study, we randomly assigned 443 patients with symptomatic pulmonary arterial hypertension to receive placebo, riociguat in individually adjusted doses of up to 2.5 mg three times daily (2.5 mg-maximum group), or riociguat in individually adjusted doses that were capped at 1.5 mg three times daily (1.5 mg-maximum group). The 1.5 mg-maximum group was included for exploratory purposes, and the data from that group were analyzed descriptively. Patients who were receiving no other treatment for pulmonary arterial hypertension and patients who were receiving endothelin-receptor antagonists or (nonintravenous) prostanoids were eligible. The primary end point was the change from baseline to the end of week 12 in the distance walked in 6 minutes. Secondary end points included the change in pulmonary vascular resistance, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, time to clinical worsening, score on the Borg dyspnea scale, quality-of-life variables, and safety.. By week 12, the 6-minute walk distance had increased by a mean of 30 m in the 2.5 mg-maximum group and had decreased by a mean of 6 m in the placebo group (least-squares mean difference, 36 m; 95% confidence interval, 20 to 52; P<0.001). Prespecified subgroup analyses showed that riociguat improved the 6-minute walk distance both in patients who were receiving no other treatment for the disease and in those who were receiving endothelin-receptor antagonists or prostanoids. There were significant improvements in pulmonary vascular resistance (P<0.001), NT-proBNP levels (P<0.001), WHO functional class (P=0.003), time to clinical worsening (P=0.005), and Borg dyspnea score (P=0.002). The most common serious adverse event in the placebo group and the 2.5 mg-maximum group was syncope (4% and 1%, respectively).. Riociguat significantly improved exercise capacity and secondary efficacy end points in patients with pulmonary arterial hypertension. (Funded by Bayer HealthCare; PATENT-1 and PATENT-2 ClinicalTrials.gov numbers, NCT00810693 and NCT00863681, respectively.).

Topics: Adult; Aged; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Endothelin Receptor Antagonists; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prostaglandins; Pyrazoles; Pyrimidines; Quality of Life; Vascular Resistance; Walking

Ambrisentan is an oral, once daily, endothelin receptor antagonist approved for treatment of pulmonary arterial hypertension (PAH). Previous studies of ambrisentan were limited to patients with Group 1 PAH and often excluded patients receiving other pulmonary hypertension (PH) therapies.. ARIES-3 was an open-label study evaluating efficacy and safety of ambrisentan in patients with various PH etiologies and background PH medications. Patients received 5 mg ambrisentan once daily for 24 weeks. The primary endpoint was change from baseline in 6-minute walk distance (6MWD) at week 24.. A total of 224 patients with PH due to idiopathic and familial PAH (31%), connective tissue disease (18%), chronic hypoxemia (22%), chronic thromboembolic disease (13%), or other etiologies (16%) were enrolled and 53% of patients received stable background PAH therapies. After 24 weeks of therapy, an increase in 6MWD (+21 m; 95% CI: 12-29) and a decrease in B-type natriuretic peptide (-26%; 95% CI: -34 to -16%) was observed in the overall population compared to baseline; however, increases in 6MWD were not observed in several non-Group 1 PH subpopulations. Peripheral edema, headache, and dyspnea were the most common adverse events.. This study reconfirms the results of previous placebo-controlled studies, which demonstrate that ambrisentan is well tolerated and provides benefit in patients with PAH. Definitive conclusions regarding the safety and efficacy of ambrisentan in specific non-Group 1 PH etiologies cannot be determined and larger, controlled studies will be necessary to determine the efficacy and safety of ambrisentan in these populations.

Topics: Adult; Aged; Double-Blind Method; Endothelin A Receptor Antagonists; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Long-Term Care; Male; Middle Aged; Natriuretic Peptide, Brain; Phenylpropionates; Pyridazines; Survival; Treatment Outcome; Walking

To evaluate the clinical utility of tissue Doppler imaging (TDI) in assessment of disease severity and prognostic value in children with idiopathic pulmonary arterial hypertension (PAH).. A prospective study was performed to evaluate TDI velocities (systolic myocardial velocity, early diastolic myocardial relaxation velocity [Em], late diastolic myocardial velocity associated with atrial contraction), brain natriuretic peptide, New York Heart Association (NYHA) functional class, and hemodynamics in 51 children (mean age; 11.6 years) with idiopathic PAH. Fifty-one healthy children with comparable demographics served as controls.. Em, Em/late diastolic myocardial velocity associated with atrial contraction ratio, and systolic myocardial velocity at mitral annulus, septum, and tricuspid annulus in PAH were significantly reduced compared with controls. Tricuspid Em had significant inverse correlations with plasma brain natriuretic peptide levels (r = -0.60, P < .001), right ventricular end-diastolic pressure (r = -0.79, P < .001), and mean pulmonary arterial pressure (r = -0.67, P < .001). Statistically significant differences were observed in tricuspid Em between NYHA functional class II vs combined III and IV (mean and SD; 11.9 ± 4.2 cm/s vs 8.2 ± 3.6 cm/s, respectively, P = .002). Cumulative event-free survival rate was significantly lower when tricuspid Em was ≤8 cm/s (log-rank test, P < .001). Tricuspid Em velocity correlated with NYHA functional class as disease severity and may serve as a useful prognostic marker in children with idiopathic PAH. The present study is the initial report to evaluate TDI velocities against midterm outcome variables in a relatively large pediatric PAH population.

Topics: Adolescent; Biomarkers; Blood Flow Velocity; Blood Pressure; Case-Control Studies; Child; Disease-Free Survival; Echocardiography, Doppler, Color; Echocardiography, Doppler, Pulsed; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Logistic Models; Male; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; ROC Curve; Severity of Illness Index

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of disease severity in pulmonary arterial hypertension (PAH). In this study we aimed to determine whether baseline NT-proBNP levels correlate with improvement in 6-minute walk distance (6MWD) in the pivotal randomized, placebo-controlled, double-blind study of the addition of inhaled treprostinil to oral therapy for PAH.. A post hoc analysis of data from the TRIUMPH-1 study was performed in patients who had assessments of NT-proBNP levels and baseline and Week 12 6MWD. Least-squares mean analysis was used to compare patients in the highest quartile of baseline NT-proBNP with those in lower quartiles with regard to change from baseline in 6MWD, stratified by treatment.. The NT-proBNP within-treatment median changes from baseline to Week 12 were +44 and -72 pg/ml, and the median changes in 6MWD from baseline to Week 12 were +5 and +40 m for the placebo (n = 94) and inhaled treprostinil (n = 84) groups, respectively. Baseline NT-proBNP levels demonstrated a strong interaction with treatment in predicting change from baseline for 6MWD (p < 0.01), indicating that, in the upper quartile (≥1,513.5 pg/ml), patients on inhaled treprostinil had a better response (+64 vs +32 m), whereas patients on placebo fared worse (-13 vs +20 m) when compared with the lower 3 quartiles (<1,513.5 pg/ml). Furthermore, least-squares mean difference in 6MWD between active and placebo groups was +67 and +16 m for the upper and lower 3 quartiles of NT-proBNP, respectively.. Greater improvement in 6MWD in actively treated patients with high levels of NT-proBNP enhances understanding of the robustness of clinical response to inhaled treprostinil in more advanced disease.

Topics: Administration, Inhalation; Adolescent; Adult; Aged; Antihypertensive Agents; Biomarkers; Double-Blind Method; Epoprostenol; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Severity of Illness Index; Time Factors; Treatment Outcome; Walking; Young Adult

Edema is a common side effect of endothelin receptor antagonists. Ambrisentan is an endothelin type A-selective endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension. We examined the clinical outcomes of patients who developed edema with and without ambrisentan treatment in 2 phase III, randomized placebo-controlled trials, ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2 (ARIES-1 and ARIES-2) (n = 393). Edema-related adverse events were extracted using broad adverse event search terms. The present post hoc analysis included 132 placebo patients and 261 ambrisentan patients. Of these patients, 14% of the placebo patients and 23% of the ambrisentan patients experienced edema-related adverse events. Overall, the patients who experienced edema tended to have a worse baseline World Health Organization (WHO) functional class (edema 76%, WHO functional class III-IV; no edema 56%, WHO functional class III-IV). In the ambrisentan patients, those with edema were older (mean age 58 ± 13 years) and heavier (mean weight 75 ± 19 kg) than those without edema (mean age 49 ± 15 years; mean weight 70 ± 17 kg). At week 12 of treatment, the ambrisentan patients had significantly increased their 6-minute walk distance (6MWD) by 34.4 m compared to the placebo patients in whom the 6MWD had deteriorated by -9.0 m (p <0.001). Among the ambrisentan patients, those without edema had a 6MWD increase of 38.9 m and those with edema had a 6MWD increase of 19.4 m. Ambrisentan significantly improved the brain natriuretic peptide levels by -34% compared to the brain natriuretic peptide levels in the placebo group that had worsened by +11% (p <0.001). Ambrisentan reduced the brain natriuretic peptide concentrations similarly in patients with and without edema. In conclusion, the present subanalysis of patients with pulmonary arterial hypertension has revealed that ambrisentan therapy provides clinical benefit compared to placebo, even in the presence of edema.

Topics: Adult; Age Factors; Aged; Analysis of Variance; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Edema; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Phenylpropionates; Pyridazines; Reference Values; Risk Assessment; Safety Management; Severity of Illness Index; Sex Factors; Treatment Outcome

The authors investigated the safety of oral tetrahydrobiopterin (BH4), a cofactor for nitric oxide synthesis, as a novel treatment for pulmonary hypertension (PH). Eighteen patients with pulmonary arterial hypertension or inoperable chronic thromboembolic PH received sapropterin dihydrochloride (6R-BH4), the optically active form of BH4, in addition to treatment with sildenafil and/or endothelin receptor antagonists in an open-label, dose-escalation study. 6R-BH4 was administered starting at a dose of 2.5 mg/kg and increasing to 20 mg/kg over 8 weeks. Changes in markers of nitric oxide synthesis, inflammation and oxidant stress, as well as exercise capacity and cardiac function were measured. 6R-BH4 was well tolerated at all doses without systemic hypotension, even when given in combination with sildenafil. There was a small but significant reduction in plasma monocyte chemoattractant protein (MCP)-1 levels on 5 mg/kg. No significant changes in measures of nitric oxide synthesis or oxidant stress were observed. There was improvement in 6-minute walk distance, most significant at a dose of 5 mg/kg, from 379 ± 61 to 413 ± 57 m 414 ± 57 m (P = .002). Oral 6R-BH4 can be administered safely in doses up to 20 mg/kg daily to patients with PH. Further studies are needed to explore its therapeutic potential.

Topics: Administration, Oral; Adult; Antihypertensive Agents; Biomarkers; Biopterins; Chemokine CCL2; Drug Therapy, Combination; Endothelin Receptor Antagonists; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; London; Male; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide; Oxidative Stress; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Recovery of Function; Sildenafil Citrate; Sulfones; Tennessee; Time Factors; Treatment Outcome; Walking

There is evidence that phosphodiesterase type-5 is effective for the treatment of pulmonary arterial hypertension (PAH).. A phase III, multicenter, open-label clinical trial of sildenafil 20mg t.i.d. was conducted in 21 Japanese patients with PAH to examine its efficacy, safety, and pharmacokinetics. The present trial consisted of a screening period and 12-week treatment. Patients who were enrolled in the present trial increased their 6-min walking distance of administration increased at week 12 by 84.2m from baseline. Hemodynamic parameters (eg, mean pulmonary artery pressure and pulmonary vascular resistance), Borg dyspnea scores, and plasma brain natriuretic peptide concentrations also improved compared to baseline. Most patients improved or sustained WHO functional class. Seven subjects, who were examined for the pharmacokinetics of sildefanil, showed relatively large interindividual variations in the C(max), AUC(0-8), C(ss,av), and C(trough) of the drug. Any serious adverse events, severe adverse events, and deaths were not observed. Most of events of undeniable causality were mild or moderate in severity. Sildefanil was well tolerated by the subjects.. Sildenafil 20mg t.i.d. was effective and safe for Japanese patients with PAH.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Blood Pressure; Female; Humans; Hypertension, Pulmonary; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vascular Resistance; Vasodilator Agents; Walking; Young Adult

Pulmonary hypertension (PH) can lead to right-side heart failure (RHF) and death. There are no therapeutic recommendations for patients experiencing acute RHF in the course of PH. This study aimed to examine the safety and efficacy of inhaled iloprost in patients with precapillary PH and RHF.. Between October 2007 and December 2008, 7 patients with precapillary PH and RHF were enrolled. Per protocol, iloprost was inhaled hourly for a minimum of 12 hours during a 24-hour period. The starting dose of 2.5 μg was increased hourly by 2.5 μg as long as the increases were tolerated. Safety and efficacy were determined by continuous invasive monitoring of systemic and pulmonary hemodynamic parameters. Systemic pressures remained stable during inhalation (66.1 ± 6.9 mm Hg at baseline and 69.1 ± 6.4 mm Hg immediately after inhalation therapy, P = 0.48). Cardiac index increased from 2.4 ± 0.7 L/min/m(2) to 2.9 ± 0.9 L/min/m(2) (P = .008). Pulmonary vascular resistance decreased from 634.6 ± 218.3 dyn·s·cm(-5) to 489.6 ± 173.8 dyn·s·cm(-5) (P = .044), and N-terminal B-type natriuretic peptide levels decreased from 13,591 ± 10,939 pg/mL to 9,944 ± 8,569 pg/mL (P = .051).. Blood pressure-guided hourly inhalation of iloprost may offer a safe and effective strategy for the treatment of PH patients with RHF.

Topics: Administration, Inhalation; Aged; Blood Pressure Determination; Female; Heart Failure; Humans; Hypertension, Pulmonary; Iloprost; Male; Middle Aged; Natriuretic Peptide, Brain; Treatment Outcome; Vasodilator Agents; Ventricular Dysfunction, Right

Relative area change (RAC) of the proximal pulmonary artery is a measurement of pulmonary artery distensibility and has been shown to correlate with vasoreactivity studies in patients with idiopathic pulmonary arterial hypertension. We have previously noted a relationship between invasive hemodynamic vasoreactivity testing and long-term response to sildenafil in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). We therefore set out to determine whether RAC can provide useful correlatory non-invasive data.. Patients recruited to a randomized, controlled trial (RCT) of sildenafil at 40 mg 3 times daily underwent additional magnetic resonance imaging (MRI) at the baseline of the trial. Eighteen patients had an MRI that led to a diagnosis of inoperable distal CTEPH or significant residual CTEPH post-operatively. The primary end-point was improvement in 6-minute walk test (6MWT) with secondary end-points of right heart catheterization-based hemodynamics, N-terminal pro-brain natriuretic peptide (NT pro-BNP) and functional class. RAC assessed by MRI was correlated with trial end-points.. Fourteen subjects with baseline MRI completed the protocol. RAC was the only baseline variable that correlated at 1 year to the primary end-point of improvement in 6MWT (r = 0.7, p = 0.006), and also to a change in NT pro-BNP (r = 0.59, p = 0.03). Using a cut-off of RAC over 20% there was an 87.5% sensitivity (95% confidence interval [CI]: 45% to 100%) and a 66.7% specificity (95% CI: 22% to 96%) for an improvement in 6MWT of >40 meters.. RAC correlates with functional response to sildenafil, as measured by the 6MWT, and improved heart function, as measured by NT pro-BNP. RAC shows potential in understanding and possibly predicting treatment response.

Topics: Adult; Aged; Cardiac Catheterization; Chronic Disease; Female; Heart; Hemodynamics; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Piperazines; Pulmonary Artery; Purines; Recovery of Function; Sensitivity and Specificity; Sildenafil Citrate; Single-Blind Method; Sulfones; Thromboembolism; Time Factors; Treatment Outcome; Vasodilator Agents; Walking

Pulmonary hypertension (PH) is a common complication of haemolytic anaemia. Intravascular haemolysis leads to nitric oxide (NO) depletion, endothelial and smooth muscle dysregulation, and vasculopathy, characterized by progressive hypertension. PH has been reported in patients with paroxysmal nocturnal haemoglobinuria (PNH), a life-threatening haemolytic disease. We explored the relationship between haemolysis, systemic NO, arginine catabolism and measures of PH in 73 PNH patients enrolled in the placebo-controlled TRIUMPH (Transfusion Reduction Efficacy and Safety Clinical Investigation Using Eculizumab in Paroxysmal Nocturnal Haemoglobinuria) study. At baseline, intravascular haemolysis was associated with elevated NO consumption (P < 0.0001) and arginase-1 release (P < 0.0001). Almost half of the patients in the trial had elevated levels (> or =160 pg/ml) of N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of pulmonary vascular resistance and right ventricular dysfunction previously shown to indicate PH. Eculizumab treatment significantly reduced haemolysis (P < 0.001), NO depletion (P < 0.001), vasomotor tone (P < 0.05), dyspnoea (P = 0.006) and resulted in a 50% reduction in the proportion of patients with elevated NT-proBNP (P < 0.001) within 2 weeks of treatment. Importantly, the significant improvements in dyspnoea and NT-proBNP levels occurred without significant changes in anaemia. These data demonstrated that intravascular haemolysis in PNH produces a state of NO catabolism leading to signs of PH, including elevated NT pro-BNP and dyspnoea that are significantly improved by treatment with eculizumab.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biomarkers; Blood Pressure; Dyspnea; Female; Hemoglobins; Hemoglobinuria, Paroxysmal; Hemolysis; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Nitric Oxide; Peptide Fragments; Treatment Outcome

This study assessed the efficacy and safety of inhaled treprostinil in pulmonary arterial hypertension (PAH) patients receiving therapy with either bosentan or sildenafil.. There is no cure for PAH, despite effective treatments, and outcomes remain suboptimal. The addition of inhaled treprostinil, a long-acting prostacyclin analog, might be a safe and effective treatment addition to other PAH-specific oral therapies.. Two hundred thirty-five PAH patients with New York Heart Association (NYHA) functional class III (98%) or IV symptoms and a 6-min walk distance (6MWD) of 200 to 450 m while treated with bosentan (70%) or sildenafil were randomized to inhaled treprostinil (up to 54 mug) or inhaled placebo 4 times daily. The primary end point was peak 6MWD at 12 weeks. Secondary end points included time to clinical worsening, Borg Dyspnea Score, NYHA functional class, 12-week trough 6MWD, 6-week peak 6MWD, quality of life, and PAH signs and symptoms. The biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) was assessed.. Twenty-three patients withdrew from the study prematurely (13 treprostinil, 10 placebo). The Hodges-Lehmann between-treatment median difference in change from baseline in peak 6MWD was 19 m at week 6 (p = 0.0001) and 20 m at week 12 (p = 0.0004). Hodges-Lehmann between-treatment median difference in change from baseline in trough 6MWD at week 12 was 14 m (p = 0.0066). Quality of life measures and NT-proBNP improved on active therapy. There were no improvements in other secondary end points, including time to clinical worsening, Borg Dyspnea Score, NYHA functional class, and PAH signs and symptoms. Inhaled treprostinil was safe and well-tolerated.. This trial demonstrates that, among PAH patients who remain symptomatic on bosentan or sildenafil, inhaled treprostinil improves exercise capacity and quality of life and is safe and well-tolerated. (TRIUMPH I: Double Blind Placebo Controlled Clinical Investigation Into the Efficacy and Tolerability of Inhaled Treprostinil Sodium in Patients With Severe Pulmonary Arterial Hypertension; NCT00147199).

Topics: Administration, Inhalation; Administration, Oral; Adult; Aged; Antihypertensive Agents; Bosentan; Drug Therapy, Combination; Epoprostenol; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Piperazines; Purines; Quality of Life; Sildenafil Citrate; Sulfonamides; Sulfones; Treatment Outcome; Vasodilator Agents; Young Adult

In animal models of pulmonary hypertension, simvastatin has been shown to reduce pulmonary artery pressure and induce regression of associated right ventricular (RV) hypertrophy.. To assess the therapeutic value of simvastatin in patients with pulmonary arterial hypertension (PAH).. Forty-two patients with PAH were randomized to receive either simvastatin (80 mg/d) or placebo in addition to current care for 6 months, and thereafter offered open-label simvastatin. The primary outcome was change in RV mass, assessed by cardiac magnetic resonance (CMR).. At 6 months, RV mass decreased by 5.2 +/- 11 g in the statin group (P = 0.045) and increased 3.9 +/- 14 g in the placebo group. The treatment effect was -9.1 g (P = 0.028). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels decreased significantly in the statin group (-75 +/- 167 fmol/ml; P = 0.02) but not the placebo group (49 +/- 224 fmol/ml; P = 0.43; overall treatment effect -124 fmol/ml; P = 0.041). There were no significant changes in other outcome measures (including 6-minute walk test, cardiac index, and circulating cytokines). From 6 to 12 months, both RV mass and NT-proBNP increased toward baseline values in 16 patients on active treatment who continued with simvastatin but remained stable in 18 patients who switched from placebo to simvastatin. Two patients required a reduction in dose but not cessation of simvastatin.. Simvastatin added to conventional therapy produces a small and transient early reduction in RV mass and NT-proBNP levels in patients with PAH, but this is not sustained over 12 months.

Topics: Adult; Aged; Antihypertensive Agents; Double-Blind Method; Female; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Simvastatin; Ultrasonography; Young Adult

Factors that determine survival in pulmonary arterial hypertension (PAH) drive clinical management. A quantitative survival prediction tool has not been established for research or clinical use.. Data from 2716 patients with PAH enrolled consecutively in the US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) were analyzed to assess predictors of 1-year survival. We identified independent prognosticators of survival and derived a multivariable, weighted risk formula for clinical use. One-year survival from the date of enrollment was 91.0% (95% confidence interval [CI], 89.9 to 92.1). In a multivariable analysis with Cox proportional hazards, variables independently associated with increased mortality included pulmonary vascular resistance >32 Wood units (hazard ratio [HR], 4.1; 95% CI, 2.0 to 8.3), PAH associated with portal hypertension (HR, 3.6; 95% CI, 2.4 to 5.4), modified New York Heart Association/World Health Organization functional class IV (HR, 3.1; 95% CI, 2.2 to 4.4), men >60 years of age (HR, 2.2; 95% CI, 1.6 to 3.0), and family history of PAH (HR, 2.2; 95% CI, 1.2 to 4.0). Renal insufficiency, PAH associated with connective tissue disease, functional class III, mean right atrial pressure, resting systolic blood pressure and heart rate, 6-minute walk distance, brain natriuretic peptide, percent predicted carbon monoxide diffusing capacity, and pericardial effusion on echocardiogram all predicted mortality. Based on these multivariable analyses, a prognostic equation was derived and validated by bootstrapping technique.. We identified key predictors of survival based on the patient's most recent evaluation and formulated a contemporary prognostic equation. Use of this tool may allow the individualization and optimization of therapeutic strategies. Serial follow-up and reassessment are warranted. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214.

Topics: Adult; Aged; Blood Pressure; Carbon Monoxide; Disease-Free Survival; Female; Heart Rate; Humans; Hypertension, Pulmonary; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prospective Studies; Registries; Renal Insufficiency; Survival Rate; Vascular Resistance

We evaluated right atrial (RA) contractility and right ventricular (RV) diastolic function in adult patients with acquired chronic pulmonary hypertension (PH) by pulsed Tissue Doppler Imaging (TDI) and assessed their relationship with serum brain natriuretic peptide (BNP).. Systolic myocardial wave (Sa), early diastolic myocardial wave (Ea), and late diastolic myocardial wave (Aa) at the tricuspid annulus were recorded in 77 consecutive patients with acquired PH. Early (E) RV inflow waves were recorded from 4-chamber views. RV Aa was regarded as the parameter of RA contractility and RV E/Ea was taken as the parameter of RV diastolic function using TDI.. All subjects had elevated BNP (mean 188.9 +/- 244.0 pg/dl) and pulmonary arterial systolic pressure (PASP) estimated at 62.9 +/- 26.7 mm Hg. BNP levels were positively correlated with RV E/Ea, Aa and PASP (r = 0.47, p < 0.0001 and r = 0.35, p < 0.01, respectively) but negatively with Aa (r = -0.29, p < 0.05). Next, all predictor variables were used in a multiple regression model with serum BNP values as dependent variables, refined to include 3 predictors: RV E/Ea, Aa, and PASP, which were all found to influence serum BNP values (p < 0.0001) by the formula Y = 34.1X1**-19.11X2**+2.95X3* (**p < 0.001, *p < 0.01) where Y = BNP, X1 = E/Ea of RV, X2 = Aa, and X3 = PASP (standard regression coefficients were 0.37, -0.34 and 0.34, respectively).. Serum BNP correlates with RA contractility and RV diastolic dysfunction by RV TDI in adults with acquired PH. Increased BNP may be related to decreased RA systolic function and RV diastolic function in these patients.

Topics: Adult; Aged; Atrial Function, Right; Biomarkers; Diastole; Echocardiography, Doppler; Feasibility Studies; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Systole; Ventricular Function, Right

The purpose of this study was to determine whether an implantable hemodynamic monitor (IHM) could be used to judge the response of pulmonary arterial hypertension (PAH) patients to changes in therapy.. A prospective, non-randomized, multi-center study evaluated physical examination, functional class, echocardiography, brain natriuretic peptide (BNP) levels, exercise capacity assessed by 6-minute walk and cardiopulmonary exercise tests, and quality of life at baseline and at 12 weeks. IHM measurements were continuously available to clinicians between clinic visits. Based on a priori, pre-specified analyses, the relationships between hemodynamic values, PAH treatments and clinical parameters were tracked in an observational fashion.. Twenty-four PAH patients underwent IHM implantation prior to a change in PAH therapy. IHM data identified 13 of the 15 patients who improved their 6-minute walk distance by >30 m at 12 weeks (+48 +/- 65 m, p < 0.05), whereas the others walked less (-78 +/- 115 m, not statistically significant). In addition, peak Vo(2), BNP levels and Minnesota Living with Heart Failure Questionnaire scores only improved in the former group. The change in mean pulmonary artery pressure correlated with the change in 6-minute walk distance at 12 weeks (r = -0.71, p < 0.001). Device-related adverse events were comparable to those known to occur with a pacemaker-like device.. Changes in ambulatory continuous hemodynamic measurements predicted changes in 6-minute walk distance after the start or addition of PAH therapy. The IHM also identified patients who had improved exercise tolerance, BNP levels and quality of life. The IHM appeared to be well tolerated and allowed rapid hemodynamic feedback between clinic visits.

Topics: Adult; Aged; Exercise Tolerance; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Monitoring, Ambulatory; Natriuretic Peptide, Brain; Predictive Value of Tests; Quality of Life; Severity of Illness Index; Walking

Ambrisentan is a propanoic acid-based, A-selective endothelin receptor antagonist for the once-daily treatment of pulmonary arterial hypertension.. Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Study 1 and 2 (ARIES-1 and ARIES-2) were concurrent, double-blind, placebo-controlled studies that randomized 202 and 192 patients with pulmonary arterial hypertension, respectively, to placebo or ambrisentan (ARIES-1, 5 or 10 mg; ARIES-2, 2.5 or 5 mg) orally once daily for 12 weeks. The primary end point for each study was change in 6-minute walk distance from baseline to week 12. Clinical worsening, World Health Organization functional class, Short Form-36 Health Survey score, Borg dyspnea score, and B-type natriuretic peptide plasma concentrations also were assessed. In addition, a long-term extension study was performed. The 6-minute walk distance increased in all ambrisentan groups; mean placebo-corrected treatment effects were 31 m (P=0.008) and 51 m (P<0.001) in ARIES-1 for 5 and 10 mg ambrisentan, respectively, and 32 m (P=0.022) and 59 m (P<0.001) in ARIES-2 for 2.5 and 5 mg ambrisentan, respectively. Improvements in time to clinical worsening (ARIES-2), World Health Organization functional class (ARIES-1), Short Form-36 score (ARIES-2), Borg dyspnea score (both studies), and B-type natriuretic peptide (both studies) were observed. No patient treated with ambrisentan developed aminotransferase concentrations >3 times the upper limit of normal. In 280 patients completing 48 weeks of treatment with ambrisentan monotherapy, the improvement from baseline in 6-minute walk at 48 weeks was 39 m.. Ambrisentan improves exercise capacity in patients with pulmonary arterial hypertension. Improvements were observed for several secondary end points in each of the studies, although statistical significance was more variable. Ambrisentan is well tolerated and is associated with a low risk of aminotransferase abnormalities.

Topics: Activities of Daily Living; Administration, Oral; Aged; Double-Blind Method; Dyspnea; Endothelin Receptor Antagonists; Exercise; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Phenylpropionates; Placebos; Pyridazines; Quality of Life; Treatment Outcome

Chronic thromboembolic pulmonary hypertension (CTEPH) results from non-resolving pulmonary thromboemboli that are resistant to plasmatic anticoagulation. Because of a secondary pulmonary arteriopathy accompanying major vessel obstruction, the disorder may be a target for vasodilator therapy.. In an open-label uncontrolled study, we investigated the prostacyclin analog treprostinil given s.c. in patients with severe inoperable CTEPH.. Between September 1999 and September 2005, 25 patients were included if their World Health Organization (WHO) functional class was III or IV, if their six-minute walking distance (6-MWD)

Topics: Aged; Antihypertensive Agents; Cardiac Output; Case-Control Studies; Chronic Disease; Epoprostenol; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Infusion Pumps; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Pain; Pain Measurement; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Pulmonary Embolism; Risk Assessment; Severity of Illness Index; Thromboembolism; Time Factors; Treatment Outcome; Vascular Resistance; Vasodilator Agents; Walking

We examined the mechanisms of renal resistance to atrial and brain natriuretic peptides (ANP and BNP) in pulmonary hypertension (PH). Compared to eight controls, nine PH patients showed a reduced ability to excrete an acute sodium load despite increased circulating ANP, BNP and cyclic guanosine monophosphate (cGMP), their second messenger. Patients' reduced urinary cGMP/BNP and natriuresis/urinary cGMP ratios demonstrated impaired generation of and reduced renal response to cGMP, respectively. Therefore, PH patients hyporesponsiveness to cardiac natriuretic peptides is likely located both upstream and downstream cGMP generation. Natriuretic peptide signalling pathway disruptions might be accessible to therapy.

Topics: Adult; Atrial Natriuretic Factor; Creatinine; Cyclic GMP; Down-Regulation; Female; Humans; Hypertension, Pulmonary; Kidney; Male; Middle Aged; Natriuresis; Natriuretic Peptide, Brain; Reference Values; Renal Insufficiency; Renin; Signal Transduction; Sodium Chloride

Patients with idiopathic pulmonary arterial hypertension usually undergo acute vasodilator tests with nitric oxide (NO) for haemodynamic evaluation and therapeutical planning. The aim of this study was to evaluate the link between the variation of N-terminal (NT)-pro-brain natriuretic peptide (BNP) levels and haemodynamic parameters during the acute vasodilator test. A total of 22 idiopathic pulmonary arterial hypertension patients who underwent acute vasodilator tests were studied. Blood samples were collected at baseline and after 30 and 60 min of NO inhalation. NT-pro-BNP levels were measured in each sample. A receiver-operating characteristic curve was used to evaluate the capability of the NT-pro-BNP level variation during NO inhalation in recognising nonresponders. To distinguish responders from nonresponders, the increase of the NT-pro-BNP (0% as cut-off value) determined a 50% specificity and 100% sensitivity (positive predictive value of 38% and a negative predictive value of 100%). These results suggest that N-terminal-pro-brain natriuretic peptide was able to distinguish nonresponder patients with the acute vasodilator test. N-terminal-pro-brain natriuretic peptide may be an interesting additional biological tool in the evaluation of idiopathic pulmonary arterial hypertension patients.

Topics: Adult; Biomarkers; Bronchial Provocation Tests; Bronchodilator Agents; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Nitric Oxide; Peptide Fragments; Sensitivity and Specificity

Phosphodiesterase type 5 (PDE5) inhibition has been proposed for the treatment for pulmonary arterial hypertension (PAH).. This study compared adding sildenafil, a PDE5 inhibitor, to conventional treatment with the current practice of adding bosentan, an endothelin receptor antagonist.. Twenty-six patients with PAH, idiopathic or associated with connective tissue disease, World Health Organization (WHO) functional class III, were randomized in a double-blind fashion to receive sildenafil (50 mg twice daily for 4 weeks, then 50 mg three times daily) or bosentan (62.5 mg twice daily for 4 weeks, then 125 mg twice daily) over 16 weeks.. Changes in right ventricular (RV) mass (using cardiovascular magnetic resonance), 6-minute walk distance, cardiac function, brain natriuretic peptide, and Borg dyspnea index.. When analyzed by intention to treat, there were no significant differences between the two treatment groups. One patient on sildenafil died suddenly. Patients on sildenafil who completed the protocol showed significant changes from baseline, namely, reductions in RV mass (-8.8 g; 95% confidence interval [CI], -2, -16; n = 13, p = 0.015) and plasma brain natriuretic peptide levels (-19.4 fmol x ml(-1); 95% CI, -5, -34; p = 0.014) and improvements in 6-minute walk distance (114 m; 95% CI, 67, 160; p = 0.0002), cardiac index (0.3 L x min(-1) x m(-2); 95% CI, 0.1, 0.4; p = 0.008), and systolic left ventricular eccentricity index (-0.2; 95% CI, -0.02, -0.37; p = 0.031). Bosentan improved 6-minute walk distance (59 m; 95% CI, 29, 89; n = 12, p = 0.001) and cardiac index (0.3; 95% CI, 0.1, 0.4; p = 0.008).. Sildenafil added to conventional treatment reduces RV mass and improves cardiac function and exercise capacity in patients with PAH, WHO functional class III. Safety monitoring is important until more experience is obtained.

Topics: Adult; Antihypertensive Agents; Bosentan; Double-Blind Method; Endothelin Receptor Antagonists; Exercise Tolerance; Female; Heart Ventricles; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Size; Phosphodiesterase Inhibitors; Piperazines; Purines; Quality of Life; Sildenafil Citrate; Sulfonamides; Sulfones; Treatment Outcome

The aim of this study was to evaluate the effect of the oral dual ET(A)/ET(B) receptor antagonist bosentan on different surrogate markers in patients with pulmonary arterial hypertension (PAH).. Prospective, open label, uncontrolled study in a University Hospital in Brazil.. Fifteen PAH patients (11 females) with mean age of 40 +/- 11 years (5 in WHO functional class II, 10 in class III).. All patients were investigated at baseline and after 16 weeks of bosentan treatment. We used the following surrogate markers for patients' evaluation: 6-min walk test, quality of life questionnaire (Short Form SF-36) and N-terminal proBNP (B type natriuretic peptide) fraction levels in blood.. Between the evaluation at baseline and week 16, the 6-min walk test distance changed from 396 +/- 135 to 434 +/- 137 m (p < 0.05). Each of the eight domains of the SF-36 was significantly improved. Mean NT-proBNP levels were decreased from a mean of 1670 pg/mL to 1010 pg/mL (p = 0.01).. The study suggests that bosentan treatment results in the improvement of different kinds of surrogate markers independently of their specificity to reflect functional capacity, quality of life and myocardial stress. It is concluded that the combined use of these different markers may be an alternative endpoint for future short duration clinical trials.

Topics: Adult; Antihypertensive Agents; Biomarkers; Bosentan; Brazil; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Quality of Life; Sulfonamides; Surveys and Questionnaires; Walking

We performed an open-label multicenter study to evaluate the safety and efficacy of the dual endothelin receptor antagonist bosentan in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH).. Nineteen patients with inoperable CTEPH were enrolled.. The primary end point was a change in pulmonary vascular resistance (PVR). Secondary end points included 6-min walk test, peak oxygen uptake (V(O2)), New York Heart Association functional class, serum levels of N-terminal-pro brain natriuretic peptide (NT-pro-BNP), and various other hemodynamic parameters.. After 3 months of treatment with bosentan, PVR decreased from 914 +/- 329 to 611 +/- 220 dyne.s.cm(-5) (p < 0.001). Functional class and peak V(O2) remained unchanged, but 6-min walk distance increased from 340 +/- 102 to 413 +/- 130 m (p = 0.009), and serum NT-pro BNP levels improved from 2,895 +/- 2,620 to 2,179 +/- 2,301 (p = 0.027). One patient died, presumably from influenza A infection, and another patient experienced progressive fluid retention despite reduction of PVR. Other than that, treatment was well tolerated by all patients.. This open-label pilot trial suggests that bosentan may offer a therapeutic option for patients with inoperable CTEPH. Randomized controlled trials are warranted to confirm these findings.

Topics: Aged; Anticoagulants; Antihypertensive Agents; Bosentan; Diuretics; Drug Therapy, Combination; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Pilot Projects; Sulfonamides; Thromboembolism; Vascular Resistance; Walking

Pulmonary arterial hypertension (PAH) leads to substantial morbidity and mortality. Noninvasive parameters in the follow-up assessment of PAH could be helpful in clinical decision making. The brain natriuretic peptide (BNP) has been shown to correlate with the functional status and prognosis of these patients and could be a valuable parameter in this respect. The aim of our study was to investigate whether BNP levels could reflect clinical and hemodynamic changes, including the response to therapy during long-term follow-up in patients with PAH.. We measured pulmonary hemodynamics, functional parameters including the 6-min walk distance (6MWD), and plasma BNP levels at baseline and after a mean (+/- SEM) follow-up period of 12.6 +/- 1.5 months in patients with PAH.. In group A (n = 18), with decreasing BNP levels mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) decreased (PAP, 60.89 +/- 3.44 to 53.47 +/- 3.24 mm Hg; PVR, 1,207.47 +/- 111.75 to 942.35 +/- 103.15 dyne.s.cm(-5); p < 0.01) and 6MWD increased (408.24 +/- 29.57 to 470 +/- 25.54 m; p < 0.01). In group B (n = 12), with increasing BNP levels mean PAP and PVR increased (PAP, 52 +/- 3.31 to 60.17 +/- 5.03 mm Hg; PVR, 946.13 +/- 115.35 to 1,236.6 +/- 180.23 dyne . s . cm(-5); p < 0.01) and mean 6MWD decreased from 463.64 +/- 27.77 to 367.27 +/- 38.87 m (p < 0.05). Comparing groups revealed statistically significant differences regarding changes in PAP (group A, -11.58 +/- 3.57%; group B, +13.29 +/- 5.44%; p = 0.001) and PVR (group A, -19.21 +/- 5.87%, group B, +30.35 +/- 7.72%; p < 0.001). Correlations existed between the changes in BNP levels and pulmonary hemodynamics.. We concluded that BNP levels parallel changes in pulmonary hemodynamics and functional parameters, including the 6MWD, in PAH patients. Consequently, we suggest BNP as a parameter for the follow-up assessment of PAH patients.

Topics: Biomarkers; Blood Pressure; Calcium Channel Blockers; Cardiac Catheterization; Exercise Test; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Time Factors; Vascular Resistance; Vasodilator Agents; Walking

Pulmonary hypertension (PH) can develop in lung fibrosis, and contributes to increased morbidity and mortality. Noninvasive parameters in the evaluation of PH in lung disease could aid in the management of these subjects. In this study, we aimed to characterize the role of brain natriuretic peptide (BNP) and the six-minute walk distance (6-MWD) in the assessment of pulmonary hypertension (PH) in subjects with lung fibrosis. Subjects with lung fibrosis and elevated BNP levels (n = 20) had significantly more severe PH during right heart catheterization than those with lung fibrosis, and normal BNP levels (mean pulmonary arterial pressure (40.85 +/- 3.2 mm Hg vs. 23.42+/-1.44 mm Hg, respectively) (n = 19) (p < 0.001). Significant correlations between lung volumes and BNP concentrations were not observed. A weak correlation existed between capillary pO(2) and 6-MWD (r = 0.42; p < 0.001). The presence of moderate-severe PH was associated with significant reduction of the 6-MWD. BNP concentrations predicted moderate-severe PH with 100% sensitivity and high specificity (89%). We conclude that BNP is an excellent marker for the presence of PH in patients with lung fibrosis. In addition, our data suggest that PH contributes significantly to exercise limitation in patients with severe lung fibrosis, raising the possibility that treatment of PH may be beneficial in these patients.

Topics: Biomarkers; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Fibrosis; Respiratory Function Tests; Sensitivity and Specificity

To evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) as a marker of early pulmonary artery hypertension (PAH) and to study changes in the levels of this marker following treatment with dihydropyridine-type calcium-channel blocker (DTCCB) in patients with systemic sclerosis (SSc).. We evaluated 40 consecutive SSc patients who had been hospitalized for followup care (mean +/- SD age 56 +/- 11 years and mean +/- SD duration of cutaneous disease 9 +/- 9 years; 27 with limited cutaneous and 13 with diffuse cutaneous disease) but who had no clinical symptoms of heart failure and had a normal left ventricular ejection fraction. At baseline, 10 patients had PAH, defined as a systolic pulmonary artery pressure (sPAP) >40 mm Hg, as measured by echocardiography. Levels of NT-proBNP were determined at baseline (after discontinuation of DTCCB treatment for 72 hours), after taking 3 doses of DTCCB following treatment reinitiation (assessment 1), and after 6-9 months of continuous DTCCB treatment (assessment 2) in the 20 patients who attended regular appointments (including the 10 patients with PAH at baseline).. At baseline, 13 patients had high NT-proBNP values for their ages. High NT-proBNP levels identified patients with PAH with a sensitivity of 90%, a specificity of 90.3%, a positive predictive value of 69.2%, and a negative predictive value of 96%. The NT-proBNP level correlated with the sPAP (r = 0.44; P = 0.006). By assessment 1, the number of patients with PAH and high levels of NT-proBNP had decreased from 9 of 10 to 2 of 10 (P = 0.02). This decrease was partially sustained at assessment 2 (4 of 10 patients; P = 0.06).. NT-proBNP is a useful biologic marker that can be used to diagnose early PAH in SSc patients without clinical heart failure. Measurement of NT-proBNP may be valuable for the evaluation of treatment with DTCCB and vasodilators in patients with PAH.

Topics: Aged; Biomarkers; Calcium Channel Blockers; Calcium Channels, L-Type; Disease Progression; Humans; Hypertension, Pulmonary; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prospective Studies; Pulmonary Artery; Scleroderma, Systemic

Plasma brain natriuretic peptide (BNP) level increases in proportion to the degree of right ventricular dysfunction in pulmonary hypertension. We sought to assess the prognostic significance of plasma BNP in patients with primary pulmonary hypertension (PPH).. Plasma BNP was measured in 60 patients with PPH at diagnostic catheterization, together with atrial natriuretic peptide, norepinephrine, and epinephrine. Measurements were repeated in 53 patients after a mean follow-up period of 3 months. Forty-nine of the patients received intravenous or oral prostacyclin. During a mean follow-up period of 24 months, 18 patients died of cardiopulmonary causes. According to multivariate analysis, baseline plasma BNP was an independent predictor of mortality. Patients with a supramedian level of baseline BNP (>/=150 pg/mL) had a significantly lower survival rate than those with an inframedian level, according to Kaplan-Meier survival curves (P<0.05). Plasma BNP in survivors decreased significantly during the follow-up (217+/-38 to 149+/-30 pg/mL, P<0. 05), whereas that in nonsurvivors increased (365+/-77 to 544+/-68 pg/mL, P<0.05). Thus, survival was strikingly worse for patients with a supramedian value of follow-up BNP (>/=180 pg/mL) than for those with an inframedian value (P<0.0001).. A high level of plasma BNP, and in particular, a further increase in plasma BNP during follow-up, may have a strong, independent association with increased mortality rates in patients with PPH.

Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Atrial Natriuretic Factor; Echocardiography; Epinephrine; Epoprostenol; Female; Follow-Up Studies; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Norepinephrine; Prognosis; Pulmonary Wedge Pressure; ROC Curve; Survival Analysis; Vasodilator Agents

Pulmonary hypertension (PH) is associated with increased mortality in patients with end-stage renal disease (ESRD). The prevalence of PH within ESRD as measured by right heart catheterization (RHC) is poorly described, and the correlation of BNP to pulmonary artery pressure (PAP) is unknown.. The renal transplant database at our center was used to identify adult ESRD patients from July 2013 to July 2015 who had a plasma BNP level measurement and invasive hemodynamic assessment by RHC within a 1-month period. Pulmonary hypertension was defined as a mean pulmonary artery pressure (PAP) ≥ 25 mmHg. Multivariate linear regression analysis was used to identify correlations between BNP and RHC parameters. To estimate the utility of BNP in the screening of PH, a receiver-operating characteristic (ROC) curve was generated.. Eighty-eight patients were included in the study of which 43 had PH. Compared to patients without PH, BNP was significantly higher within the PH cohort (1619 ± 2602 pg/ml vs. 352 ± 491 pg/ml). A statistically significant association (r [86] = 0.60, p<0.001) between plasma BNP and mean PAP was identified. ROC curve indicated an acceptable predictive value of BNP in PH with a c-statistic of 0.800 (95% CI 0.708 - 0.892).. In ESRD patients being considered for renal transplantation, PH is highly prevalent and BNP levels are elevated and significantly correlated with higher PAP. BNP may be a useful non-invasive marker of PH in these patients.

Topics: Adult; Biomarkers; Brain; Hemodynamics; Humans; Hypertension, Pulmonary; Kidney Failure, Chronic; Natriuretic Peptide, Brain; Renal Dialysis

A diagnosis of idiopathic pulmonary arterial hypertension (IPAH) is frequently made in elderly patients who present with comorbidities, especially hypertension, coronary heart disease, diabetes mellitus, and obesity. It is unknown to what extent the presence of these comorbidities affects the response to PAH therapies and whether risk stratification predicts outcome in patients with comorbidities.. We assessed the database of COMPERA, a European pulmonary hypertension registry, to determine changes after initiation of PAH therapy in WHO functional class (FC), 6-minute walking distance (6MWD), brain natriuretic peptide (BNP) or N-terminal fragment of probrain natriuretic peptide (NT-pro-BNP), and mortality risk assessed by a 4-strata model in patients with IPAH and no comorbidities, 1-2 comorbidities and 3-4 comorbidities.. The analysis was based on 1,120 IPAH patients (n = 208 [19%] without comorbidities, n = 641 [57%] with 1-2 comorbidities, and n = 271 [24%] with 3-4 comorbidities). Improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk from baseline to first follow-up were significantly larger in patients with no comorbidities than in patients with comorbidities, while they were not significantly different in patients with 1-2 and 3-4 comorbidities. The 4-strata risk tool predicted survival in patients without comorbidities as well as in patients with 1-2 or 3-4 comorbidities.. Our data suggest that patients with IPAH and comorbidities benefit from PAH medication with improvements in FC, 6MWD, BNP/NT-pro-BNP, and mortality risk, albeit to a lesser extent than patients without comorbidities. The 4-strata risk tool predicted outcome in patients with IPAH irrespective of the presence of comorbidities.

Topics: Aged; Familial Primary Pulmonary Hypertension; Follow-Up Studies; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Arterial Hypertension; Risk Assessment

Pulmonary hypertension has been reported as a crucial factor in the pathophysiology of severe bronchiolitis. The aim of this study was to evaluate pulmonary artery pressure (PAP) in patients with bronchiolitis and to analyze their correlation with clinical outcomes. This prospective cohort study examined children admitted for bronchiolitis. PAP was assessed by right ventricle (RV) acceleration/ejection time ratio (AT/ET), isovolumic relaxation time, eccentricity index, and the presence of a pulmonary systolic notch. Pulmonary hypertension (PH) was considered if at least two altered parameters were present. Severity of clinical course was established by higher N-terminal (NT)-prohormone BNP (NT-proBNP) values, the need for positive pressure respiratory support (PPRS), and the duration of hospital admission. One hundred sixty-nine children were included in analysis. Sixty-eight patients (40%) required PPRS, and those patients had increased NT-proBNP values and worse tricuspid annular systolic excursion (TAPSE) compared to mild cases (p < 0.001and p < 0.001, respectively). Twenty-two (13%) cases had at least two altered parameters of PAP and met criteria for presumed PH, with no differences in NT-proBNP values, TAPSE, need for PPRS or hospital length of stay compared to normal PAP group (p = 0.98, p = 0.07, p = 0.94 and p = 0.64, respectively). We found no correlation between altered RV AT/ET and worse cardiac function, NT-proBNP values or hospital length of stay. In our cohort, the presence of echocardiographic findings of PH were not associated with worse clinical outcomes. Patients with severe bronchiolitis had higher values ​​of NT-proBNP but, interestingly, no clear association with PH.

Topics: Biomarkers; Bronchiolitis; Child; Echocardiography; Humans; Hypertension, Pulmonary; Infant; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

Risk stratification and assessment of disease progression in patients with pulmonary arterial hypertension (PAH) are challenged by the lack of accurate disease-specific and prognostic biomarkers. To date, brain natriuretic peptide (BNP) and/or its N-terminal fragment (NT-proBNP) are the only markers for right ventricular dysfunction used in clinical practice, in association with echocardiographic and invasive haemodynamic variables to predict outcome in patients with PAH.. This study was designed to identify an easily measurable biomarker panel in the serum of 80 well-phenotyped PAH patients with idiopathic, heritable or drug-induced PAH at baseline and at first follow-up. The prognostic value of identified cytokines of interest was secondly analysed in an external validation cohort of 125 PAH patients.. Among the 20 biomarkers studied with the multiplex Ella platform, we identified a three-biomarker panel composed of β-NGF, CXCL9 and TRAIL that were independently associated with prognosis both at the time of PAH diagnosis and at the first follow-up after initiation of PAH therapy. β-NGF and CXCL9 were predictors of death or transplantation, whereas high levels of TRAIL were associated with a better prognosis. Furthermore, the prognostic value of the three cytokines was more powerful for predicting survival than usual non-invasive variables (New York Heart Association Functional Class, 6-min walk distance and BNP/NT-proBNP). The results were validated in a fully independent external validation cohort.. The monitoring of β-NGF, CXCL9 and TRAIL levels in serum should be considered in the management and treatment of patients with PAH to objectively guide therapeutic options.

Topics: Biomarkers; Cytokines; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a complex disease characterized by progressive right ventricular (RV) failure leading to significant morbidity and mortality. Investigating metabolic features and pathways associated with RV dilation, mortality, and measures of disease severity can provide insight into molecular mechanisms, identify subphenotypes, and suggest potential therapeutic targets.. We collected data from a prospective cohort of PAH participants and performed untargeted metabolomic profiling on 1045 metabolites from circulating blood. Analyses were intended to identify metabolomic differences across a range of common metrics in PAH (eg, dilated versus nondilated RV). Partial least squares discriminant analysis was first applied to assess the distinguishability of relevant outcomes. Significantly altered metabolites were then identified using linear regression, and Cox regression models (as appropriate for the specific outcome) with adjustments for age, sex, body mass index, and PAH cause. Models exploring RV maladaptation were further adjusted for pulmonary vascular resistance. Pathway enrichment analysis was performed to identify significantly dysregulated processes.. A total of 117 participants with PAH were included. Partial least squares discriminant analysis showed cluster differentiation between participants with dilated versus nondilated RVs, survivors versus nonsurvivors, and across a range of NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, REVEAL 2.0 composite scores, and 6-minute-walk distances. Polyamine and histidine pathways were associated with differences in RV dilation, mortality, NT-proBNP, REVEAL score, and 6-minute walk distance. Acylcarnitine pathways were associated with NT-proBNP, REVEAL score, and 6-minute walk distance. Sphingomyelin pathways were associated with RV dilation and NT-proBNP after adjustment for pulmonary vascular resistance.. Distinct plasma metabolomic profiles are associated with RV dilation, mortality, and measures of disease severity in PAH. Polyamine, histidine, and sphingomyelin metabolic pathways represent promising candidates for identifying patients at high risk for poor outcomes and investigation into their roles as markers or mediators of disease progression and RV adaptation.

Topics: Heart Failure; Histidine; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Pulmonary Arterial Hypertension; Sphingomyelins

Connective tissue growth factor (CTGF) has diagnostic value for pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) in children; however, its value in adult patients remains unclear. This study evaluated CTGF as a biomarker in adult PAH-CHD patients.Methods and Results: Based on mean pulmonary artery pressure (mPAP), 56 CHD patients were divided into 3 groups: without PAH (W; mPAP <25 mmHg; n=28); mild PAH (M; mPAP 25-35 mmHg; n=18); and moderate and severe PAH (H; mPAP ≥35 mmHg; n=10). The control group consisted of 28 healthy adults. Plasma CTGF and B-type natriuretic peptide (BNP) concentrations were determined. Plasma CTGF concentrations were higher in the H and M groups than in the W and control groups, and were higher in the H than M group. Plasma CTGF concentrations were positively correlated with pulmonary artery systolic pressure (PASP), mPAP, and pulmonary vascular resistance, and negatively correlated with mixed venous oxygen saturation. CTGF, BNP, red blood cell distribution width, and World Health Organization Class III/IV were risk factors for PAH in CHD patients, and CTGF was an independent risk factor for PAH-CHD. The efficacy of CTGF in the diagnosis of PAH was not inferior to that of BNP.. CTGF is a biomarker of PAH associated with CHD. It can be used for early diagnosis and severity assessment in adult patients with CHD-PAH.

Topics: Adult; Biomarkers; Child; Connective Tissue Growth Factor; Familial Primary Pulmonary Hypertension; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Pulmonary Arterial Hypertension

Pulmonary arterial hypertension is a common complication in patients with congenital heart disease. In the absence of early diagnosis and treatment, pediatric patients with PAH has a poor survival rate. Here, we explore serum biomarkers for distinguishing children with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) from CHD.. Samples were analyzed by nuclear magnetic resonance spectroscopy-based metabolomics and 22 metabolites were further quantified by ultra-high-performance liquid chromatography-tandem mass spectroscopy.. Serum levels of betaine, choline, S-Adenosyl methionine (SAM), acetylcholine, xanthosine, guanosine, inosine and guanine were significantly altered between CHD and PAH-CHD. Logistic regression analysis showed that combination of serum SAM, guanine and N-terminal pro-brain natriuretic peptide (NT-proBNP), yielded the predictive accuracy of 157 cases was 92.70% with area under the curve of the receiver operating characteristic curve value of 0.9455.. We demonstrated that a panel of serum SAM, guanine and NT-proBNP is potential serum biomarkers for screening PAH-CHD from CHD.

Topics: Biomarkers; Child; Familial Primary Pulmonary Hypertension; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Metabolomics; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Arterial Hypertension

The aim of this observational study was to investigate the influence of different typical preterm diseases on NT-proBNP serum levels in the early postnatal period of life of a preterm infant. NT-proBNP levels of 118 preterm infants born ≤ 31 weeks GA were determined at the first week of life, after 4 ± 1 weeks of life, and at a corrected gestational age of 36 + 2 weeks. Relevant complications with a possible influence on NT-proBNP values in the first week of life such as early neonatal infection, hemodynamically significant PDA (hsPDA), early pulmonary hypertension (early PH), and intraventricular hemorrhage (IVH) were evaluated; at 4 ± 1 weeks of life, bronchopulmonary dysplasia (BPD), BPD-related pulmonary hypertension (BPD-associated PH), late infection, IVH, and intestinal complications were evaluated. At a corrected gestational age of 36 ± 2 weeks, we examined the effect of retinopathy of prematurity (ROP), BPD, BPD-associated PH, and late infection on NT-proBNP levels. In the first days of life, only the isolated occurrence of hsPDA resulted in significantly increased NT-proBNP levels. In multiple linear regression analysis, early infection remained independently associated with NT-proBNP levels. At 4 ± 1 weeks of age, the isolated presence of BPD and BPD-related PH resulted in increased levels, and the effect remained significant in the multiple regression analysis. At a corrected gestational age of 36 ± 2 weeks, infants with relevant complications at this final evaluation time tended to have lower NT-proBNP values than our exploratory reference values.    Conlusion: NT-proBNP in the first week of life seems to be mainly influenced by an hsPDA and infection or inflammation. BPD and BPD-related PH are the most important factors influencing NT-proBNP serum levels in the first month of life. When preterm infants reach a corrected GA of 36 ± 2 weeks, chronological age rather than complications of prematurity must be considered when interpreting NT-proBNP levels. What is Known: • Several complications associated with prematurity, such as hemodynamically significant PDA, pulmonary hypertension, bronchopulmonary dysplasia, and retinopathy of prematurity, have been shown to influence NT-proBNP levels in preterm infants in their early postnatal life. What is New: • Hemodynamically relevant PDA is a major factor in the increase of NT-proBNP levels in the first week of life. • Bronchopulmonary dysplasia and pulmonary hypertension associated with bronchopulmon

Topics: Biomarkers; Bronchopulmonary Dysplasia; Ductus Arteriosus, Patent; Gestational Age; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Infant, Premature; Natriuretic Peptide, Brain; Retinopathy of Prematurity

Pulmonary hypertension (PH) is a severe hemodynamic condition with high morbidity and mortality. Approved targeted therapies are limited for pediatric subjects, and treatments are widely adopted from adult algorithms. Macitentan is a safe and effective drug used for adult PH, but data on pediatric patients are limited. In this prospective single-center study, we investigated mid- and long-term effects of macitentan in children with advanced pulmonary hypertensive vascular disease.. Twenty-four patients were enrolled in the study for treatment with macitentan. Efficacy was determined by echo parameters and brain natriuretic peptide levels (BNP) at 3 months and 1 year. For detailed analysis, the entire cohort was subgrouped into patients with congenital heart disease-related PH (CHD-PH) and non-CHD-PH patients, respectively.. Mean age of the patients was 10.7 ± 7.6 years; median observation period was 36 months. Twenty of 24 patients were on additional sildenafil and/or prostacyclins. Two of 24 patients discontinued because of peripheral edema. Within the entire cohort, BNP levels and all echo measures such as right ventricular systolic pressure (RVSP), right ventricular end-diastolic diameter (RVED), tricuspid annular plane systolic excursion (TAPSE), pulmonary velocity time integral (VTI), and pulmonary artery acceleration time (PAAT) improved significantly after 3 months (p ≤ 0.01), whereas in the long term significant improvement persisted for BNP levels (-16%), VTI (+14%) and PAAT (+11%) (p < 0.05). By subgroup analysis, non-CHD PH patients showed significant improvements in BNP levels (-57%) and all echo measures (TAPSE +21%, VTI +13%, PAAT +37%, RVSP -24%, RVED -12%) at 3 months (p ≤ 0.01), whereas at 12 months, improvements persisted (p < 0.05) except for RVSP and RVED (nonsignificant). In CHD-PH patients, none of the measures changed (nonsignificant). 6-MWD (distance walked in 6 minutes) slightly increased but was not statistically evaluated.. Data presented herein account for the largest cohort of severely affected pediatric patients receiving macitentan. Overall, macitentan was safe and associated with significant beneficial effects and sustained positive signals after 1 year, albeit in the long term disease progression remains a major concern. Our data suggest limited efficacy in CHD-related PH, whereas favorable outcomes were mainly driven by improvements in patients with PH not related to CHD. Larger studies are needed to verify these preliminary results and to prove efficacy of this drug in different pediatric PH entities.

Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Prospective Studies; Sulfonamides; Tertiary Care Centers

Risk assessment is recommended for patients with congenital heart disease-associated pulmonary arterial hypertension. This study aims to compare an abbreviated version of the risk assessment strategy, noninvasive French model, and an abridged version of the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management 2.0 risk score calculator, Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2.. We enrolled a mixed prevalent and incident cohort of patients with congenital heart disease-associated pulmonary arterial hypertension (n = 126). Noninvasive French model comprising World Health Organization functional class, 6-minute walk distance, and N-terminal pro-hormone of brain natriuretic peptide or brain natriuretic peptide was used. Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2 includes functional class, systolic blood pressure, heart rate, 6-minute walk distance, brain natriuretic peptide/N-terminal pro-hormone of brain natriuretic peptide, and estimated glomerular filtration rate.. The mean age was 32.17 ± 16.3 years. The mean follow-up was 99.41 ± 58.2 months. Thirty-two patients died during follow-up period. Most patients were Eisenmenger syndrome (31%) and simple defects (29.4%). Most patients received monotherapy (76.2%). Most patients were World Health Organization functional class I-II (66.6%). Both models effectively identified risk in our cohort (P =.0001). Patients achieving 2 or 3 noninva-sive low-risk criteria or low-risk category by Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2 at follow-up had a significantly reduced risk of death. Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2 approximates noninvasive French model at discriminating among patients based on c-index. Age, high risk by Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2, and the presence of 2 or 3 low-risk criteria by noninvasive French model emerged as an independent predictors of mortality (multivariate hazard ratio: 1.031, 95% CI: 1.005-1.058, P =.02; hazard ratio: 4.258, CI: 1.143-15.860, P =.031; hazard ratio: 0.095, CI: 0.013-0.672, P =.018, respectively).. Both abbreviated risk assessment tools may provide a simplified and robust method of risk assessment for congenital heart disease-associated pulmonary arterial hypertension. Patients not achieving low risk at follow-up may benefit from aggressive use of available therapies.

Topics: Adolescent; Adult; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Arterial Hypertension; Risk Assessment; Young Adult

In recent years, the usefulness of echocardiography and serum biomarkers in the diagnosis of pulmonary hypertension (PH) in dogs with heartworm disease has been studied. Previously, N-terminal pro B-type natriuretic peptide (NT-proBNP) has shown high concentrations in dogs with heart disease and/or PH as well as its usefulness as a prognostic indicator, but it has never been evaluated in the diagnosis and prognosis of PH in dogs with heartworm disease. The aim was to evaluate the serum concentrations of NT-proBNP in dogs infected by Dirofilaria immitis to determine its usefulness as a tool to detect precapillary PH.. NT-proBNP was determined in 50 heartworm-infected dogs. Presence/absence of PH was determined echocardiographically, using the Right Pulmonary Artery Distensibility Index (RPAD Index) and the systolic flow of tricuspid regurgitation mainly, together with other echocardiographic measurements following the guidelines of the American College of Veterinary Internal Medicine (ACVIM) for the diagnosis of PH. Other epidemiological parameters (breed, age, sex, status: client-owned or shelter dogs) and clinical parameters (microfilaremia, parasite burden, presence of symptoms, body condition) were collected as well.. Moderate-severe PH was present in 40% of the dogs (RPAD Index < 29.5%), NT-proBNP concentrations being significantly higher compared with dogs that did not have PH. A cutoff for NT-proBNP of ≥ 1178.45 pmol/l showed a sensitivity of 64.3% and a specificity of 95.5% for the presence of moderate-severe PH. Older dogs and dogs from shelters showed significantly higher NT-proBNP concentrations. Dogs with symptoms and low body condition presented significantly higher NT-proBNP concentrations as well.. The determination of NT-pro-BNP concentration can be a useful tool in the diagnostic work-up of dogs with heartworm disease and associated PH and can help to identify animals in the more advanced stage of this disorder.

Topics: Animals; Biomarkers; Dirofilaria immitis; Dirofilariasis; Dogs; Heart Diseases; Hypertension, Pulmonary; Natriuretic Peptide, Brain

To investigate the relationship between the neutrophil-to-lymphocyte ratio and chronic obstructive pulmonary disease complicated with pulmonary hypertension (COPD + PH).. We retrospectively analyzed clinical data from 242 COPD patients at our hospital from July 2018 to July 2019. Patients underwent examinations including blood analysis, C-reactive protein, N-terminal brain natriuretic peptide (BNP), pulmonary function, and cardiac color ultrasound.. Patients were divided into the COPD and COPD + PH groups using pulmonary arterial pressure (<50 and ≥50 mmHg, respectively). Compared with the COPD group, the COPD + PH group had greater pulmonary arterial pressure, smoking history, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, BNP, Chronic Obstructive Pulmonary Disease Assessment Test score, and right atrium and ventricular diameters, but smaller body mass index, forced vital capacity, lymphocyte count, and left ventricular diameter. BNP and NLR had positive effects on PH; forced vital capacity had a negative impact. Moreover, BNP (area under the curve [AUC] = 0.748, sensitivity = 0.692, specificity = 0.701) and NLR (AUC = 0.679, sensitivity = 0.831, specificity = 0.452) had predictive value for PH, and both were positively correlated with PH.. NLR is associated with COPD + PH, and may be useful for its diagnosis.

Topics: C-Reactive Protein; Humans; Hypertension, Pulmonary; Lymphocytes; Natriuretic Peptide, Brain; Neutrophils; Pulmonary Disease, Chronic Obstructive; Retrospective Studies

To evaluate the performance of pulmonary hypertension (PH) biomarkers in children with Down syndrome, an independent risk factor for PH, in whom biomarker performance may differ compared with other populations.. Serum endostatin, interleukin (IL)-1 receptor 1 (ST2), galectin-3, N-terminal pro hormone B-natriuretic peptide (NT-proBNP), IL-6, and hepatoma-derived growth factor (HDGF) were measured in subjects with Down syndrome and PH (n = 29), subjects with Down syndrome and resolved PH (n = 13), subjects with Down syndrome without PH (n = 49), and subjects without Down syndrome with World Symposium on Pulmonary Hypertension group I pulmonary arterial hypertension (no Down syndrome PH group; n = 173). Each biomarker was assessed to discriminate PH in Down syndrome. A classification tree was created to distinguish PH from resolved PH and no PH in children with Down syndrome.. Endostatin, galectin-3, HDGF, and ST2 were elevated in subjects with Down syndrome regardless of PH status. Not all markers differed between subjects with Down syndrome and PH and subjects with Down syndrome and resolved PH. NT-proBNP and IL-6 levels were similar in the Down syndrome with PH group and the no Down syndrome PH group. A classification tree identified NT-proBNP and galectin-3 as the best markers for sequentially distinguishing PH, resolved PH, and no PH in subjects with Down syndrome.. Proteomic markers are used to improve the diagnosis and prognosis of PH but, as demonstrated here, can be altered in genetically unique populations such as individuals with Down syndrome. This further suggests that clinical biomarkers should be evaluated in unique groups with the development of population-specific nomograms.

Topics: Adolescent; Biomarkers; Case-Control Studies; Child; Child, Preschool; Down Syndrome; Endostatins; Female; Galectin 3; Humans; Hypertension, Pulmonary; Intercellular Signaling Peptides and Proteins; Interleukin-6; Male; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Interleukin-1

Risk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). The current European guidelines propose a three-stratum model to categorise risk as low, intermediate or high, based on the expected 1-year mortality. However, with this model, most patients are categorised as intermediate risk. We investigated a modified approach based on four risk categories, with intermediate risk subdivided into intermediate-low and intermediate-high risk.. We analysed data from the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA), a European pulmonary hypertension registry, and calculated risk at diagnosis and first follow-up based on World Health Organization functional class, 6-min walk distance (6MWD) and serum levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), using refined cut-off values. Survival was assessed using Kaplan-Meier analyses, log-rank testing and Cox proportional hazards models.. Data from 1655 patients with PAH were analysed. Using the three-stratum model, most patients were classified as intermediate risk (76.0% at baseline and 63.9% at first follow-up). The refined four-stratum risk model yielded a more nuanced separation and predicted long-term survival, especially at follow-up assessment. Changes in risk from baseline to follow-up were observed in 31.1% of the patients with the three-stratum model and in 49.2% with the four-stratum model. These changes, including those between the intermediate-low and intermediate-high strata, were associated with changes in long-term mortality risk.. Modified risk stratification using a four-stratum model based on refined cut-off levels for functional class, 6MWD and BNP/NT-proBNP was more sensitive to prognostically relevant changes in risk than the original three-stratum model.

Topics: Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Arterial Hypertension; Registries; Risk Assessment

There remains a lack of prognosis models for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study aims to develop a nomogram predicting 3-, 5-, and 7-year survival in patients with CTEPH and verify the prognostic model. Patients with CTEPH diagnosed in Fuwai Hospital were enrolled consecutively between May 2013 and May 2019. Among them, 70% were randomly split into a training set and the other 30% as a validation set for external validation. Cox proportional hazards model was used to identify the potential survival-related factors which were candidate variables for the establishment of nomogram and the final model was internally validated by the bootstrap method. A total of 350 patients were included in the final analysis and the median follow-up period of the whole cohort was 51.2 months. Multivariate analysis of Cox proportional hazards regression showed body mass index, mean right atrial pressure, N-terminal pro-brain natriuretic peptide (per 500 ng/ml increase in concentration), presence of anemia, and main treatment choice were the independent risk factors of mortality. The nomogram demonstrated good discrimination with the corrected C-index of 0.82 in the training set, and the C-index of 0.80 (95% CI: 0.70 to 0.91) in the external validation set. The calibration plots also showed a good agreement between predicted and actual survival in both training and validation sets. In conclusion, we developed an easy-to-use nomogram with good apparent performance using 5 readily available variables, which may help physicians to identify CTEPH patients at high risk for poor prognosis and implement medical interventions.

Topics: Adult; Aged; Anemia; Angioplasty, Balloon; Antihypertensive Agents; Atrial Pressure; Body Mass Index; Chronic Disease; Clinical Decision Rules; Endarterectomy; Endothelin Receptor Antagonists; Enzyme Activators; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mortality; Multivariate Analysis; Natriuretic Peptide, Brain; Nomograms; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Prognosis; Proportional Hazards Models; Pulmonary Artery; Pulmonary Embolism; Pulmonary Wedge Pressure; Pyrazoles; Pyrimidines; Reproducibility of Results; Survival Rate

Pulmonary arterial hypertension (PAH) is a severe complication of CTD, being one of the leading causes of mortality for patients with this condition. Soluble suppression of tumorigenicity 2 (sST2) is a novel biomarker associated with adverse clinical outcomes in cardiovascular patients. In this study, we investigated the role of sST2 as a predictor of poor clinical outcome in patients with CTD associated with pulmonary hypertension (CTD-PH).. This retrospective cohort study enrolled 71 CTD-PH patients diagnosed by echocardiography. Twenty-one CTD patients without PH were selected for a control group. A receiver operating characteristic (ROC) curve assessed the predictive value of sST2 in assessing 3-year clinical worsening. Hazard ratios associated with potential predictors of clinical worsening were estimated using Cox proportional hazard models. The primary end point was clinical worsening.. The level of sST2 was significantly elevated in CTD-PH patients compared with the control group. After a mean follow-up of 25.29 (1.88) months, end point events occurred in 26 patients. sST2 was an independent predictor of clinical worsening and all-cause death in patients with CTD-PH. sST2 ≥ 39.99 ng/ml discriminated 3-year clinical worsening with a sensitivity and specificity of 100% and 84.9%, respectively. The patients with both higher levels of sST2 (≥39.99 ng/ml) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (≥300 ng/l) had the worst prognosis.. sST2 ≥ 39.99 ng/ml predicts higher incidence of clinical worsening events in CTD-PH patients. Furthermore, patients with elevated sST2 had significantly worse prognosis among those with high NT-proBNP.

Topics: Biomarkers; Connective Tissue Diseases; Humans; Hypertension, Pulmonary; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies

The prognostic value of improvement endpoints that have been used in clinical trials of treatments for pulmonary arterial hypertension (PAH) needs to be further investigated.. Using the COMPERA database, we evaluated the prognostic value of improvements in functional class (FC) and absolute or relative improvements in 6-min walking distance (6MWD) and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP). In addition, we investigated multicomponent endpoints based on prespecified improvements in FC, 6MWD and NT-proBNP that have been used in recent PAH trials. Finally, we assessed the predictive value of improvements determined by risk stratification tools. The effects of changes from baseline to first follow-up (3-12 months after initiation of PAH therapy) on consecutive survival were determined by Kaplan-Meier analysis with Log-Rank testing and Cox proportional hazard analyses.. All analyses were based on 596 patients with newly diagnosed PAH for whom complete data were available at baseline and first follow-up. Improvements in FC were associated with improved survival, whereas absolute or relative improvements in 6MWD had no predictive value. For NT-proBNP, absolute declines conferred no prognostic information while relative declines by ≥35% were associated with better survival. Improvements in multicomponent endpoints were associated with improved survival and the same was found for risk stratification tools.. While sole improvements in 6MWD and NT-proBNP had minor prognostic relevance, improvements in multicomponent endpoints and risk stratification tools based on FC, 6MWD, and NT-proBNP were associated with improved survival. These tools should be further explored as outcome measures in PAH trials.

Topics: Biomarkers; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Arterial Hypertension; Treatment Outcome

The aim of the study was to evaluate the levels of cardiac biomarkers endothelin 1, B-natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (Nt-proBNP), NO

Topics: Biomarkers; COVID-19; Endothelin-1; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Nitrates; Nitrites; Nitrogen Dioxide; Oxygen; Peptide Fragments

Atrial septal defect developed pulmonary hypertension (ASD-PH) at first diagnosis due to late presentation are common in Indonesia. Transthoracic echocardiogram (TTE) is a common tool to detect ASD-PH, before proceeding to invasive procedure. The NT-proBNP measurement to screen ASD-PH is not yet considered the standard approach, especially in limited resource conditions. The objective of this study is to assess the value of NT-proBNP, along with simple TTE parameter, to screen PH among adults with ASD.. This was a cross-sectional study. The subjects were adult ASD-PH patients from the COHARD-PH  registry (n=357). Right heart catheterization (RHC) was performed to diagnose PH. Blood sample was withdrawn during RHC for NT-proBNP measurement. The TTE was performed as standard procedure and its regular parameters were assessed, along with NT-proBNP, to detect PH.. Two parameters significantly predicted PH, namely NT-proBNP and right atrial (RA) diameter. The cut-off of NT-proBNP to detect PH was ≥140 pg/mL. The cut-off of RA diameter to detect PH was ≥46.0 mm. The combined values of NT-proBNP level ≥140 pg/mL and RA diameter ≥46.0 mm yielded 46.6% sensitivity, 91.8% specificity, 54.3% accuracy, 96.5% positive predictive value and 26.2% negative predictive value to detect PH, which were better than single value.. NT-proBNP level ≥140 pg/mL represented PH in adult ASD patients. The NT-proBNP level ≥140 pg/mL and RA diameter ≥46.0 mm had a pre-test probability measures to triage patients needing more invasive procedure and also to determine when and if to start the PH-specific treatment.

Topics: Adult; Atrial Fibrillation; Biomarkers; Cross-Sectional Studies; Heart Septal Defects, Atrial; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments

Pulmonary arterial hypertension (PAH) is a serious complication of SSc with high mortality. Interventricular systolic asynchrony (IVSA) is observed in PAH patients, but the effect of IVSA and its association with long-term mortality and clinical events in SSc-associated PAH are unclear. This study aimed to investigate the impact of IVSA on the prognosis of SSc-associated PAH.. Between March 2010 and July 2018, a total of 60 consecutive patients with SSc-associated PAH were enrolled. The end point was a composite of all-cause mortality and clinical worsening. Asynchrony was assessed by colour-coded tissue Doppler imaging (TDI) echocardiography. The myocardial sustained systole curves (Sm) of the basal portion of the right ventricular (RV) free wall and left ventricular (LV) lateral wall were obtained. IVSA was defined as the time difference from the onset of the QRS complex to the end of Sm between LV and RV.. Patients with greater IVSA time differences presented with advanced pulmonary vascular resistance (PVR). The IVSA time difference was an independent predictive factor (Hazard Ratio (HR) = 1.018, 95% CI: 1.005, 1.031, P =0.005) for the composite end point and was significantly associated with PVR (r = 0.399, R2=0.092, P =0.002). Kaplan-Meier survival curves showed that patients with greater IVSA had worse prognoses (log-rank P =0.001).. In conclusion, IVSA analysed by colour-coded TDI echocardiography provided added value as a noninvasive, easy-to-use approach for assessing the prognosis of patients with SSc-associated PAH. A significant IVSA time difference identifies the subgroup of patients at high risk of a poor prognosis.

Topics: Echocardiography, Doppler, Color; Female; Follow-Up Studies; Heart Ventricles; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Scleroderma, Systemic; Systole; Vascular Resistance

This retrospective cohort study aimed to explore the relationship between temporal changes in the cardiac function and peripartum cardiac events in pregnant women with low-risk congenital heart disease.We performed echocardiography at early and late pregnancy and postpartum in 76 pregnant women with low-risk congenital heart disease, and compared echocardiographic parameters between subjects with and without peripartum cardiac events. Median age at delivery was 27 (range, 24-31) years. The ZAHARA and CARPREG II scores suggested that most women were found to be at low-risk for pregnancy. Fifteen subjects had cardiac events that included heart failure in 10, arrhythmia in 4, and pulmonary hypertension in one subject. The left ventricular and atrial volumes significantly increased from early pregnancy toward late pregnancy, and the E/A ratio and global longitudinal strain significantly decreased from early pregnancy toward late pregnancy. The left atrial volume (67 [53-79] versus 45 [35-55] mL, P = 0.002) and plasma brain natriuretic peptide level (58 [36-123] versus 34 [18-48] pg/mL, P = 0.026) at late pregnancy were significantly higher in subjects with cardiac events than in those without cardiac events.An increase in the left atrial volume followed by mild left ventricular diastolic dysfunction is related to peripartum cardiac events in women with congenital heart disease who are at low risk for cardiac events during pregnancy.

Topics: Adult; Arrhythmias, Cardiac; Case-Control Studies; Diastole; Echocardiography; Female; Heart Atria; Heart Defects, Congenital; Heart Failure; Heart Ventricles; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peripartum Period; Postpartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Retrospective Studies; Risk Assessment; Time Factors; Ventricular Dysfunction, Left

Patients with acute decompensation of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) admitted to intensive care unit (ICU) have high in-hospital mortality. We hypothesized that pulmonary hypertension (PH) severity, measured by a simplified version of European Society of Cardiology/European Respiratory Society (ESC/ERS) risk assessment, and the severity of organ dysfunction upon ICU admission, measured by sequential organ failure assessment score (SOFA) were associated with in-hospital mortality in decompensated patients with PAH and CTEPH. We also described clinical and laboratory variables during ICU stay.. Observational study including adults with decompensated PAH or CTEPH with unplanned ICU admission between 2014 and 2019. Multivariate logistic regression models were used to evaluate the association of ESC/ERS risk assessment and SOFA score with in-hospital mortality. ESC/ERS risk assessment and SOFA score were included in a decision tree to predict in-hospital mortality.. 73 patients were included. In-hospital mortality was 41.1%. ESC/ERS high-risk group (adjusted odds ratio = 95.52) and SOFA score (adjusted odds ratio = 1.80) were associated with in-hospital mortality. The decision tree identified four groups with in-hospital mortality between 8.1% and 100%. Nonsurvivors had a lower central venous oxygen saturation, higher arterial lactate and higher brain natriuretic peptide in the end of first week in the ICU.. High-risk on a simplified version of ERS/ESC risk assessment and SOFA score upon ICU admission are associate with in-hospital mortality. A decision tree based on ESC/ERS risk assessment and SOFA score identifies four groups with in-hospital mortality between 8.1% and 100%.

Topics: Adult; Brazil; Cohort Studies; Female; Hospital Mortality; Humans; Hypertension, Pulmonary; Intensive Care Units; Lactic Acid; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Dysfunction Scores; Oxygen Saturation; Prognosis; Retrospective Studies; Severity of Illness Index

Despite several therapies, pulmonary hypertension (PH) is still a severe disease which can lead to right heart failure. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in cardiac and vascular remodeling in PH. Therefore, these biomarkers play an important role in PH patients. This study investigated whether TIMP-4, MMP-2, and N-terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) plasma levels are useful in assessing the severity of PH and other clinical or echocardiographic parameters.. The concentrations of MMP-2, TIMP-4, and NT-proBNP in 68 PH patients were compared with those of 12 controls without PH. All patients underwent a physical examination, echocardiography, and were checked for the presence of cardiovascular risk factors; also, plasma concentrations of MMP-2, TIMP-4, NT-proBNP, total cholesterol, and triglycerides were determined.. In PH patients, significantly elevated plasma levels of TIMP-4 (PH: 2877.99 ± 1363.78 pg/ml, control: 2028.38 ± 762.67 pg/ml, p = 0.0068) and NT-proBNP ( PH: 2405.00 pg/ml-5423.47 ± 6703.38 pg/ml, control: 411.0000 pg/ml-421.75 ± 315.37 pg/ml, p = 0.01) were detected. We also observed that MMP-2 and NT-proBNP were significantly increased in patients with higher WHO functional class (p = 0.001 for MMP-2, p = 0.008 for NT-proBNP), higher pressure in the pulmonary artery (p = 0.002 for MMP-2, p = 0.001 for NT-proBNP), and more severe tricuspid regurgitation (p = 0.001 for MMP-2, p = 0.009 for NT-proBNP). TIMP-4 was elevated in patients with more severe pressure in the pulmonary artery (p = 0.006).. The plasma levels of TIMP-4 and NT-proBNP are higher in PH patients. MMP-2 and NT-proBNP correlates with different PH parameters severity (WHO functional class, sPAP severity, TV regurgitation severity). Therefore, plasmatic levels of MMP-2 and NT-proBNP at this kind of patients reflect disease severity and may have a prognostic role. MMP-2 can help assess the beneficial effects of PH pharmacotherapy on tissue remodeling. These remodeling biomarkers may not have a diagnostic value but they have the potential to predict survival. Nevertheless, a greater understanding of the involvement of MMPs in PH is mandatory to further explore the prognostic role and the possibilities of therapeutic MMP inhibition in PH.

Topics: Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Echocardiography, Doppler, Color; Female; Humans; Hypertension, Pulmonary; Male; Matrix Metalloproteinase 2; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Severity of Illness Index; Tissue Inhibitor of Metalloproteinase-4; Tissue Inhibitor of Metalloproteinases; Vascular Remodeling

Pulmonary hypertension (PH) is one of the common complications in chronic obstructive pulmonary disease (COPD). The study aimed to evaluate the predicting ability of N-terminal pro brain natriuretic peptide (NT-pro BNP) in patients with AECOPD-PH and its relationship with the severity of PH.. A large retrospective case-controlled study (n = 1072) was performed in the First Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2020, and patients were divided into stable COPD (n = 178), AECOPD (n = 688) and AECOPD-PH group (n = 206). Different statistical models were used to screen for reliable and stable biomarkers.. In unadjusted analysis and PSM (model 1, 2, 3), red cell distribution width (RDW), total bilirubin (TBIL), and NT-pro BNP were higher in patients with AECOPD-PH than those in AECOPD group. Logistic regression analysis showed, when the range of NT-proBNP was 271-1165 pg/mL (OR: 0.293; 95%CI: 0.184-0.467; P < 0.001) and NT-proBNP > 1165 pg/mL (OR: 0.559; 95%CI: 0.338-0.926; P = 0.024), the morbidity risk of PH in AECOPD patients was increased, so did TBIL. In receiver operating characteristic (ROC) curves, at the cut-off value of NT-proBNP was 175.14 pg/mL, AUC was 0.651 (P < 0.001), which was better than TBIL (AUC: 0.590, P < 0.001). As for the results of rank correlation analysis, NT-proBNP had a weak correlation with severity of PH with AECOPD (r. Our findings suggest that NT-proBNP has a diagnostic efficacy in AECOPD-PH and NT-proBNP has a weak correlation with severity of PH with AECOPD.

Topics: Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Disease, Chronic Obstructive; Retrospective Studies

While the performance of the emPHasis-10 (e10) score has been evaluated against limited patient characteristics within the United Kingdom, there is an unmet need for exploring the performance of the e10 score among pulmonary arterial hypertension (PAH) patients in the United States.. Using the Pulmonary Hypertension Association Registry, we evaluated relationships between the e10 score and demographic, functional, haemodynamic and additional clinical characteristics at baseline and over time. Furthermore, we derived a minimally important difference (MID) estimate for the e10 score.. We analysed data from 565 PAH (75% female) adults aged mean±sd 55.6±16.0 years. At baseline, the e10 score had notable correlation with factors expected to impact quality of life in the general population, including age, education level, income, smoking status and body mass index. Clinically important parameters including 6-min walk distance and B-type natriuretic peptide (BNP)/N-terminal proBNP were also significantly associated with e10 score at baseline and over time. We generated a MID estimate for the e10 score of -6.0 points (range -5.0--7.6 points).. The e10 score was associated with demographic and clinical patient characteristics, suggesting that health-related quality of life in PAH is influenced by both social factors and indicators of disease severity. Future studies are needed to demonstrate the impact of the e10 score on clinical decision-making and its potential utility for assessing clinically important interventions.

Topics: Adult; Aged; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Arterial Hypertension; Quality of Life; United Kingdom

No prior proteomic screening study has centred on the right ventricle (RV) in pulmonary arterial hypertension (PAH). This study investigates the circulating proteomic profile associated with right heart maladaptive phenotype (RHMP) in PAH.Plasma proteomic profiling was performed using multiplex immunoassay in 121 (discovery cohort) and 76 (validation cohort) PAH patients. The association between proteomic markers and RHMP, defined by the Mayo right heart score (combining RV strain, New York Heart Association (NYHA) class and N-terminal pro-brain natriuretic peptide (NT-proBNP)) and Stanford score (RV end-systolic remodelling index, NYHA class and NT-proBNP), was assessed by partial least squares regression. Biomarker expression was measured in RV samples from PAH patients and controls, and pulmonary artery banding (PAB) mice.High levels of hepatocyte growth factor (HGF), stem cell growth factor-β, nerve growth factor and stromal derived factor-1 were associated with worse Mayo and Stanford scores independently from pulmonary resistance or pressure in both cohorts (the validation cohort had more severe disease features: lower cardiac index and higher NT-proBNP). In both cohorts, HGF added value to the REVEAL score in the prediction of death, transplant or hospitalisation at 3 years. RV expression levels of HGF and its receptor c-Met were higher in end-stage PAH patients than controls, and in PAB mice than shams.High plasma HGF levels are associated with RHMP and predictive of 3-year clinical worsening. Both HGF and c-Met RV expression levels are increased in PAH. Assessing plasma HGF levels might identify patients at risk of heart failure who warrant closer follow-up and intensified therapy.

Topics: Animals; Cohort Studies; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Mice; Natriuretic Peptide, Brain; Proteomics; Pulmonary Arterial Hypertension

Clinical studies suggest that diabetes is a risk factor in the development of pulmonary arterial hypertension. The increase in blood pressure in the pulmonary area is characterized by the increase in the afterload and hypertrophy of the right ventricle. The objective of this study was to conduct a longitudinal follow-up of the morphological and functional changes in the right ventricle in a rat model with pulmonary arterial hypertension secondary to diabetes. Male Sprague Dawley rats were randomly divided into a control group (saline solution) and a diabetic group (60 mg/kg with streptozotocin). For 12 weeks, an echocardiography for longitudinal (

Topics: Animals; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Experimental; Diastole; Echocardiography; Follow-Up Studies; Heart Failure; Heart Rate; Heart Ventricles; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Rats, Sprague-Dawley; Risk Factors; Streptozocin; Systole; Vascular Remodeling

Topics: Heart Diseases; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments

End points that are repeatable and sensitive to change are important in pulmonary arterial hypertension (PAH) for clinical practice and trials of new therapies. In 42 patients with PAH, test-retest repeatability was assessed using the intraclass correlation coefficient and treatment effect size using Cohen's d statistic. Intraclass correlation coefficients demonstrated excellent repeatability for MRI, 6 min walk test and log to base 10 N-terminal pro-brain natriuretic peptide (log

Topics: Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Arterial Hypertension; Stroke Volume; Ventricular Function, Right; Walk Test

Although cardiac catheterisation (cath) is the diagnostic test for pulmonary hypertension, it is an invasive procedure. Echocardiography (echo) is commonly used for the non-invasive diagnosis of pulmonary hypertension but maybe limited by lack of adequate signals. Therefore, emphasis has been placed on biomarkers as a potential diagnostic tool. No prior paediatric studies have simultaneously compared N-terminal pro-B-type-natriuretic peptide (NTproBNP) with cath/echo as a potential diagnostic tool. The aim of this study was to determine if NTproBNP was a reliable diagnostic tool for pulmonary hypertension in this population.. Patients were divided into Study (echo evidence/established diagnosis of pulmonary hypertension undergoing cath) and Control (cath for small atrial septal defect/patent ductus arteriosus and endomyocardial biopsy post cardiac transplant) groups. NTproBNP, cath/echo data were obtained.. Thirty-one patients met inclusion criteria (10 Study, 21 Control). Median NTproBNP was significantly higher in the Study group. Echo parameters including transannular plane systolic excursion z scores, pulmonary artery acceleration time and right ventricular fractional area change were lower in the Study group and correlated negatively with NTproBNP. Receiver operation characteristic curve analysis demonstrated NTproBNP > 389 pg/ml was 87% specific for the diagnosis of pulmonary hypertension with the addition of pulmonary artery acceleration time improving the specificity.. NTproBNP may be a valuable adjunctive diagnostic tool for pulmonary hypertension in the paediatric population. Echo measures of transannular plane systolic excursion z score, pulmonary artery acceleration time and right ventricular fractional area change had negative correlations with NTproBNP. The utility of NTproBNP as a screening tool for pulmonary hypertension requires validation in a population with unknown pulmonary hypertension status.

Topics: Biomarkers; Child; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

Topics: Heart Diseases; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments

Critically ill Covid-19 pneumonia patients are likely to develop the sequence of acute pulmonary hypertension, right ventricular (RV) strain, and eventually RV failure due to known pathophysiology (endothelial inflammation plus thrombo-embolism) that promotes increased pulmonary vascular resistance and pulmonary artery pressure. This study aimed to investigate the occurrence of acute pulmonary hypertension (aPH) as per established trans-thoracic echocardiography (TTE) criteria in Covid-19 patients receiving intensive care and to explore whether short-term outcomes are affected by the presence of aPH.. Medical records were reviewed for patients treated in the intensive care units at a tertiary university hospital over a month. The presence of aPH on the TTE was noted, and plasma NTproBNP and troponin were measured as markers of cardiac failure and myocardial injury, respectively. Follow-up data were collected 21 d after the performance of TTE.. In total, 26 of 67 patients (39%) had an assessed systolic pulmonary artery pressure of > 35 mmHg (group aPH), meeting the TTE definition of aPH. NTproBNP levels (median [range]: 1430 [102-30 300] vs. 470 [45-29 600] ng L. TTE-defined acute pulmonary hypertension was frequently observed in severely ill Covid-19 patients. Furthermore, aPH was linked to biomarker-defined myocardial injury and cardiac failure, as well as an almost sevenfold increase in 21-d mortality.

Topics: Acute Disease; Adult; Aged; Biomarkers; COVID-19; Critical Care; Echocardiography; Female; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Heart Failure; Hospital Mortality; Humans; Hypertension, Pulmonary; Intensive Care Units; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Procedures and Techniques Utilization; Respiration, Artificial; Retrospective Studies; SARS-CoV-2; Sweden; Tertiary Care Centers; Treatment Outcome; Tricuspid Valve Insufficiency; Troponin T

Heart failure (HF) is growing in importance as a significant cause of disease and mortality. When It is suspected, it can be ruled out if BNP values are below 100 pg/mL. Diagnostic certainty can be obtained if echocardiogram shows reduced ejection fraction, diastolic dysfunction or right-sided heart disease. Physiological changes at high altitude are known to affect BNP values. This study pretends to evaluate BNP values when used for HF diagnosis in Huancayo, Perú, a high altitude population located at 3,250 m above sea level.. This is a cross-sectional, diagnostic test type study. A total of 83 medical charts of patients with suspected HF, admitted to the Emergency Room and Internal Medicine Service of Ramiro Prialé Prialé National Hospital, were reviewed. Data processing was performed with SPSS program for Windows version 21.0. Pearson's Chi Square test was used for categorical variables analysis and ANOVA for continuos variables. P values under 0.05 were considered significant.. Medium age was 74 years. Patient's characteristics that were associated with confirmed HF and high BNP levels were the following: presence of fatigue, night cough, elevated heart rate, shortness of breath, history of lung fibrosis and decreased oxygen arterial saturation (p < 0.05) Pulmonary hypertension, mitral and tricuspid regurgitation, and cor pulmonale were also associated with higher BNP levels. Most subjects had BNP values >100 pg/mL, with low specificity for HF diagnosis (11.5 %). Individuals without heart failure had mean BNP values above 300 pg/mL; while individuals with cor pulmonale had a mean of 975 pg/mL. BNP values were high in patients with or without HF. A cut-off point of ≥130pg/mL is proposed to increase specificity. The predictive capacity of BNP for HF identification at this high altitude population is low because of a high number of false positive results.

Topics: Adult; Aged; Aged, 80 and over; Altitude; Cross-Sectional Studies; Echocardiography, Doppler; Female; Heart Failure; Humans; Hypertension, Pulmonary; Hypoxia; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Peru; Vital Capacity

Topics: Biomarkers; Heart Failure; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments

The role of lipocalin 2 (LCN2) in pulmonary hypertension (PH) in pediatric patients with congenital heart disease (CHD) remains unclear. We sought to investigate whether LCN2 could be a potential biomarker for PH in pediatric patients who underwent surgery for CHD. From December 2018 to February 2020, patients undergoing surgical repair for congenital defects with and without PH were identified. Healthy children without CHD and PH served as controls. A mean pulmonary artery pressure (mPAP) >20 mmHg was used as the definition of PH. Blood samples and echocardiograms were obtained in all patients and right heart catheterization was performed in 79 patients. Multivariable logistic regression analysis was used to determine potential predictors for PH. Among 102 patients, the median age was 10 [Interquartile range (IQR) 7.0-13] months, and 37.5% were female. Compared to non-PH patients and controls, PH patients showed elevated levels of LCN2 (

Topics: Adolescent; Biomarkers; Child; Echocardiography; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Lipocalin-2; Male; Natriuretic Peptide, Brain; Peptide Fragments

Topics: Aged; Blood Gas Analysis; Cardiac Catheterization; Female; Guideline Adherence; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Polysomnography; Prospective Studies; Sleep Apnea, Obstructive; Unnecessary Procedures; Walk Test

Pulmonary hypertension (PH) is a substantial preoperative risk factor. For this study, morbidity and mortality were examined after noncardiac surgery in patients with precapillary PH.. A retrospective cohort study.. Quaternary medical center in Rochester, MN.. Adults with PH undergoing noncardiac surgery.. None.. The PH and surgical databases were reviewed from 2010 to 2017. Patients were excluded if PH was attributable to left-sided heart disease or they had undergone cardiac or transplantation surgeries. To assess whether PH-specific diagnostic or cardiopulmonary testing parameters were predictive of perioperative complications, generalized estimating equations were used. Of 196 patients with PH, 53 (27%) experienced 1 or more complications, including 5 deaths (3%) within 30 days. After adjustment for age and PH type, there were more complications in those undergoing moderate- to high-risk versus low-risk procedures (odds ratio [OR] 4.17 [95% confidence interval {CI} 2.07-8.40]; p < 0.001). After adjustment for age, surgical risk, and PH type, the complication risk was greater for patients with worse functional status (OR 2.39 [95% CI 1.19-4.78]; p = 0.01 for classes III/IV v classes I/II) and elevated serum N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) (OR 2.28 [95% CI 1.05-4.96]; p = 0.04 for ≥300 v <300 pg/mL). After adjusting for age, surgical risk, and functional status, elevated NT-proBNP remained associated with increased risk (OR 2.23 [95% CI 1.05-4.76]; p = 0.04).. PH patients undergoing noncardiac surgery have a high frequency of complications. Worse functional status, elevated serum NT-proBNP, and higher-risk surgery are predictive of worse outcome.

Topics: Biomarkers; Cohort Studies; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Complications; Predictive Value of Tests; Retrospective Studies; Risk Factors

Quantification of hemodynamics and right ventricular (RV) function is crucial for pulmonary hypertension (PH). Cardiovascular magnetic resonance-based heart deformation analysis (CMR-HDA) has been used to assess the ventricular strain.. This study was to determine the correlation of right ventricular longitudinal strain (RVLS) assessed with CMR-HDA with RV function as well as hemodynamics in patients with chronic thromboembolic pulmonary hypertension (CTEPH).. Thirty-six CTEPH patients were prospectively included in this research. Each patients underwent CMR and right heart catheterization (RHC). RVLS and RV ejection fraction (RVEF) was quantified from cine images acquired with a retrospectively gated turbo FLASH gradient-echo sequence. The late gadolinium enhancement (LGE) images were acquired using a 2D inversion recovery phase-sensitive fast gradient-echo sequence. Hemodynamics were determined with RHC.. Right ventricular longitudinal strain measured with CMR-HDA was -13.99 ± 4.94%. Bland-Altman plots showed statistical agreement with RVLS with low intra- and interobserver variability. RVLS correlated with serum N-terminal-pro-B-type natriuretic peptide (r = 0.615, P < .001). RVLS inversely correlated with RVEF (r = -0.699, P < .001), and it was positively correlated with both RVESV (r = 0.664, P < .001) and myocardial the volume of LGE (r = 0.447, P = .008). Receiver-operating characteristic (ROC) indicated that RVLS values of >-14.20% could be used to predict RVEF <40% with a 100% sensitivity and a 96.7% specificity. Hemodynamically, RVLS was positively correlated with mean pulmonary artery pressure (r = 0.598, P < .001) and pulmonary vascular resistance (r = 0.685, P < .001).. Right ventricular longitudinal strain assessed by CMR-HDA is a readily available and reproducible parameters of RV function. RVLS >-14.20% suggests the presence of RV dysfunction.

Topics: Adult; Cardiac Catheterization; Chronic Disease; Contrast Media; Echocardiography; Female; Gadolinium; Hemodynamics; Humans; Hypertension, Pulmonary; Image Interpretation, Computer-Assisted; Magnetic Resonance Spectroscopy; Male; Middle Aged; Natriuretic Peptide, Brain; Observer Variation; Peptide Fragments; Pulmonary Embolism; Pulmonary Wedge Pressure; Retrospective Studies; Sensitivity and Specificity; Stroke Volume; Vascular Resistance; Ventricular Dysfunction, Right; Ventricular Function, Right

This pilot study aimed to determine the feasibility of urinary NT-proBNP (NT-proBNP) as a potential noninvasive screening marker for pulmonary hypertension (PH).. A prospective cross-sectional study was conducted. Preterm infants (PI) (birthweight <1500 gm and <30 weeks gestational age (GA)) were enrolled. Serial urinary NT-proBNP measurements and echocardiograms (ECHO) were performed at 28, 32, and 36 weeks.. Thirty-six patients were included in the final analysis (BPD-PH group = 6, BPD group = 20, control = 10). Urinary NT-proBNP levels were higher in the BPD-PH group compared with BPD and control groups at all study intervals. A urine NT-proBNP cutoff level of 2345 pg/ml at 28 weeks of GA had a sensitivity and specificity of 83.3% and 84.2%, respectively, for detection of BPD-PH (AUC 0.816, p = 0.022).. Urinary NT-proBNP measurement is feasible in preterm infants and appears to be a good noninvasive screening tool for PH.

Topics: Adult; Biomarkers; Cross-Sectional Studies; Echocardiography; Female; Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Maternal Age; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Prospective Studies; ROC Curve; Sensitivity and Specificity

Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the leading causes of pulmonary hypertension (PH). We aimed to investigate the outcome of CTEPH patients who were followed-up by a PH outpatient clinic.. We screened the medical records of 29 PH patients who were followed-up by a PH outpatient clinic between 2009 and 2018. The patients' demographics and their clinical, echocardiographic, and hemodynamic characteristics were recorded.. Our study group consisted of 16 females (55.2%) and 13 males (44.8%). The mean age was 59.5±13.7 years and the median follow-up duration was 44 months (1-113 months). The mean initial 6-minute walking distance (6MWD) was 321.4±119.9 m. The initial median N-terminal pro brain natriuretic peptide (NT-proBNP) level was 2468 pg/mL (46.1-20.564 pg/mL). All patients were on oral anticoagulant therapy. Pulmonary endarterectomy (PEA) was performed in 17 of 29 patients (58.6%). Twelve patients (41.4%) were not operated upon due to distal disease, comorbidities, or their own preference. The operated patients were younger than the non-operated patients (55 years & 65 years, p=0.04). At the follow-up, the 6MWD in the operated patients increased (+76 m) and decreased in non-operated patients (-46 m). The survival rate at 10-year follow-up was 58.6% for the whole group. Twelve patients died during the follow-up period. While 7 of 12 not-operated patients died (58.3%), just 5 of 17 operated patients (4 perioperatively and 1 at follow-up) died (29%). Advanced-stage final functional capacity (FC) [New York Heart Association (NYHA) III-IV], inoperability, lower final 6MWD, higher final NT-proBNP, and reduced tricuspid annular plane systolic excursion (TAPSE) were associated with an increased mortality rate. Univariate Cox regression analysis showed that patients with NYHA I-II final FC showed a 166-fold decreased mortality rate.. The long-term prognosis of operated patients is better than the outcome of not-operated patients. The strongest predictor associated with mortality was a worse final FC (NYHA III-IV).

Topics: Aged; Echocardiography; Female; Hemodynamics; Hospitals, University; Humans; Hypertension, Pulmonary; Male; Medical Records; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Survival Analysis; Turkey

Pulmonary hypertension (PH) has been described in myelofibrosis (MF), but it is rare and typically found in advanced disease. Although the etiology of PH in MF is unclear, early predictors may be detected by echocardiogram. The goals of our study were to evaluate the prevalence of PH as determined by echocardiography in a cohort of MF patients and to identify clinical risk factors for PH. We performed a retrospective review of MF patients from October 2015 to May 2017 at MD Anderson Cancer Center in the ambulatory clinic, and those with echocardiogram were included. Clinical, echocardiographic, and laboratory data were reviewed. Patients with and without PH were compared using a chi-square or Fisher's exact test, and logistic regression was performed with an outcome variable of PH. There were 143 patients with MF who underwent echocardiogram, and 20 (14%) had echocardiographic findings consistent with PH. Older age, male gender, hypertension, hyperlipidemia, coronary artery disease, dyspnea, hematocrit, brain natriuretic peptide (BNP), and N-terminal prohormone BNP (NT-proBNP) were significantly different between those without PH and those with PH (p < 0.05). Female gender was protective (OR 0.21, 95% CI 0.049-0.90, p = 0.035), and NT-proBNP was a significant clinical predictor of PH (OR 1.07, CI 1.02 = 1.12, p = 0.006). PH in MF is lower than previously reported in our MF cohort, but many patients had cardiac comorbidities. PH due to left-sided heart disease may be underestimated in MF. Evaluation of respiratory symptoms and elevated NT-proBNP should prompt a baseline echocardiogram. Early detection of PH with a multidisciplinary approach may allow treatment of reversible etiologies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Comorbidity; Coronary Disease; Dyspnea; Echocardiography; Female; Humans; Hyperlipidemias; Hypertension; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Primary Myelofibrosis; Retrospective Studies; Young Adult

In recent years, several treatment options for patients with pre-capillary pulmonary hypertension (PH) have improved the short-term prognosis. However, the long-term survival for pre-capillary PH has not been well investigated. This study sought to investigate the long-term survival for pre-capillary PH in Kurume University Hospital. A total of 144 patients with pre-capillary PH (110 women, mean age 55.1 ± 17.9 years) were enrolled. The maximal duration of followup was 15 years with a mean followup of 5.77 years. The 15 year survival was 59.1% for pre-capillary PH, 68.5% for pulmonary arterial hypertension (PAH), and 44.3% for chronic thromboembolic PH. The 5 year survival was 50.9% for PH due to lung disease (PH-LD), indicating the worst in the pre-capillary PH subgroups. The survival for portopulmonary hypertension was the lowest among PAH groups, and PAH associated with connective tissue disease and congenital heart disease decreased 10 years after diagnosis. A 6 min walk distance and elevated brain natriuretic peptide were significantly associated with survival outcome in pre-capillary PH patients and diastolic pulmonary arterial pressure was related to survival for PH-LD. The survivals were different among pre-capillary PH groups in our hospital. Above all, the long-term survival was better than in previous reports.

Topics: Adult; Aged; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Proportional Hazards Models; Risk Assessment; Survival Rate; Walk Test

Pulmonary hypertension (PH) is a common comorbidity of cardiopulmonary disease. Endostatin, an inhibitor of angiogenesis, is elevated in neonates with lung disease. ST2 is a heart failure biomarker correlated with PH in adults. We hypothesized that these biomarkers may be useful in diagnosing PH and categorizing its severity in infants.. Endostatin, ST2, and NT-proBNP plasma concentrations from 26 infants with PH and 21 control infants without PH were correlated with echocardiographic and clinical features using regression models over time.. Endostatin, ST2, and NT-proBNP concentrations were elevated in PH participants versus controls (p < 0.0001). Endostatin was associated with right ventricular dysfunction (p = 0.014), septal flattening (p = 0.047), and pericardial effusion (p < 0.0001). ST2 concentrations predicted right to left patent ductus arteriosus flow (p = 0.009). NT-proBNP was not associated with PH features.. Endostatin and ST2 concentrations were associated with echocardiographic markers of worse PH in infants and may be better predictors than existing clinical standards.

Topics: Adult; Biomarkers; Ductus Arteriosus, Patent; Echocardiography; Endostatins; Female; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Interleukin-1 Receptor-Like 1 Protein; Male; Natriuretic Peptide, Brain; Peptide Fragments

Severity of lung hypoplasia, pulmonary hypertension (PH) and cardiac dysfunction are major contributors to mortality in congenital diaphragmatic hernia (CDH). Therefore, early assessment and management is important to improve outcome. NT-proBNP is an established cardiac biomarker with only limited data for early postnatal risk assessment in CDH newborns.. To investigate the correlation of NT-proBNP at birth, 6 h, 12 h, 24 h, and 48 h with PH and cardiac dysfunction and the prognostic information of NT-proBNP for the use of ECMO support or mortality.. 44 CDH newborns treated at our institution (December 2014-October 2017) were prospectively enrolled.. Primary clinical endpoint was either need for ECMO or death within the first 48 h (group A). Infants not receiving ECMO support were allocated to group B. Mortality was tested as secondary endpoint.. NT-proBNP levels measured at 6 h, 12 h, 24 h and 48 h postpartum correlated significantly with PH severity following NICU admission and at 24 h, and with severity of cardiac dysfunction at birth, 24 h, 48 h and after 7 days of life. There was no difference in NT-proBNP levels between survivors and non-survivors. NT-proBNP levels were significantly higher in group A at 6 h (p = 0.007), 12 h (p = 0.036), and 24 h (p = 0.007), but not at birth (p = 0.785) or 48 h (p = 0.15) compared to group B.. NT-proBNP analysis in the first 48 h of life may be useful to assess PH and cardiac dysfunction in CDH newborns and to predict the need for ECMO support.

Topics: Electrocardiography; Extracorporeal Membrane Oxygenation; Female; Fetal Blood; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Infant; Infant Mortality; Infant, Newborn; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies

We did a comparative analysis of matched and mismatched defects in pre- and post-operative V/Q scans in CTEPH patients. We correlated the number of these defects with pre-operative clinical and hemodynamic parameters.. This was a retrospective study on 27 patients with CTEPH who underwent surgery. Pre- and post-operative V/Q scans were graded for each lung segment as normal, matched or mismatched defect. Additional pre- and post-operative clinical and hemodynamic parameters that were collected include New York Heart Association functional class, six-minute walk distance in feet, N-terminal pro b-type natriuretic peptide, forced expiratory volume in one second/forced vital capacity, diffusing capacity of the lung for carbon monoxide, pulmonary arterial pressure (systolic, diastolic and mean), right atrial pressure, cardiac output and cardiac index. Pulmonary vascular resistance was then calculated.. On a segmental basis, 176 mismatched defects were noted in 27 patients, of which 111 improved post-surgery (63%). 22 of the 34 matched defects improved following surgery (64%). 31 new mismatched defects were observed. The number of pre-operative matched defects per patient ranged from 0 to 6. No statistically significant associations were observed between the number of pre-operative matched defects and pre-operative clinical parameters. No statistically significant associations were observed between the number of improved matched defects and the change in clinical parameters (pre- to post-surgery).. Both matched and mismatched defects on preoperative V/Q scans can show normalization post-surgery. The extent of matched defects on a preoperative V/Q scan does not correlate significantly with other clinical and hemodynamic parameters.

Topics: Chronic Disease; Female; Humans; Hypertension, Pulmonary; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Retrospective Studies; Ventilation-Perfusion Scan

Adiponectin is a biomarker closely related to heart failure. However, its role in pulmonary hypertension remains unclear. In this study, we investigated the association between adiponectin and hemodynamic abnormalities, right ventricular function in patients with congenital heart disease associated pulmonary hypertension (CHD-PH).. Patients with CHD-PH were enrolled in this cross-sectional study. Linear regression analysis was performed to assess the association between adiponectin, N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) and different clinical parameters. Results were depicted as beta-estimates(ß) with 95%-confidence intervals (95% CI). In addition, mediation and receiver operating characteristic curve analyses were used to analyze the relationships among adiponectin, NT-proBNP and right ventricular function.. A total of 86 CHD-PH patients were included. The overall mean adiponectin concentration was 7.9 ± 5.8 μg/ml. Log adiponectin was positively correlated with pulmonary circulation index (ß = 2.2, 95% CI 0.5, 4.0), log NT-proBNP (ß = 0.22, 95% CI 0.04, 0.41) and inversely with the tricuspid annular plane systolic excursion (TAPSE, ß = -4.7, 95% CI -8.6, - 0.8). The mediation analysis revealed the association between NT-proBNP and TAPSE was fully mediated by adiponectin (total effect c = - 5.4, 95% CI -9.4, - 1.5, p = 0.013; direct effect c' = - 3.7, 95% CI -7.5, 0.1, p = 0.067). Additionally, the efficiency of adiponectin for detecting right ventricular dysfunction was not inferior to NT-proBNP (AUC = 0.84, 95% CI 0.67-1.00 vs AUC = 0.74, 95% CI 0.51-0.97, p = 0.23).. Adiponectin is closely correlated with pulmonary blood flow and right ventricular function and may be a valuable biomarker for disease assessment in patients with pulmonary hypertension.

Topics: Adiponectin; Adult; Area Under Curve; Biomarkers; Cross-Sectional Studies; Echocardiography; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Circulation; ROC Curve; Ventricular Dysfunction, Right; Young Adult

Functional status assessed by the WHO-FC scale derived from adults is a known prognostic factor for pulmonary hypertension. Data on the usefulness of the Panama-FC scale in assessing children with pulmonary hypertension are limited. The study was performed to compare functional status results (WHO-FC and Panama-FC) and to assess the usefulness of these scales in various clinical situations. The reliability of the Panama-FC questionnaire method for facilitating patient evaluation was also examined. 26 functional status assessments (7 in disease progression/after treatment intensification) in both scales were analyzed in 19 patients with PAH confirmed in RHC. WHO-FC, Panama-FC scales, and questionnaire-based on Panama-FC were conducted independently by three different physicians. Results of assessments were compared with each other and with 6MWD, NTproBNP level, and echo parameters (TAPSE, RV/LV ratio). The Panama-FC scale results obtained using the medical interview method and questionnaire did not differ. Both WHO-FC and Panama-FC classes well-reflected disease advancement confirmed by non-invasive parameters (NTproBNP, 6MWD, TAPSE, RV/LV ratio). Differences between grading the class in both scales were observed: 5pts were classified to II (Panama-FC) vs I (WHO-FC), 2pts were in lower risk group in WHO-FC (II) vs Panama (IIIa). Worsening or improvement after treatment intensification in functional status in both scales was connected with the significant change of NTproBNP level. The 6-min walking distance did not change. TAPSE, RV/LV ratio changed significantly in 3pts with IPAH, accordingly to change in WHO-FC and Panama-FC. WHO-FC and Panama-FC well reflect the disease advancement. The questionnaire method simplified the use of the Panama-FC scale. The Panama-FC scale appears to be better for assessing functional status during long-term follow-up, while the WHO-FC scale was more useful in short-term treatment monitoring.

Topics: Adolescent; Child; Child, Preschool; Disease Progression; Female; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Reproducibility of Results; Risk Factors; Surveys and Questionnaires

Diazoxide, a drug used to treat hyperinsulinemic hypoglycemia (HH), is associated with pulmonary hypertension (PH), as reported by the US Food and Drug Administration. However, no report has detailed the association between diazoxide dose and PH development. We report a case of an infant with HH, subsequently complicated by diazoxide-induced PH. When diazoxide was introduced, PH did not appear initially, but it developed during increased dosing. We monitored PH via regular echocardiography examinations. PH gradually improved with tapering of the diazoxide dose and disappeared after drug discontinuation. Our case suggests a diazoxide dose threshold might induce PH. Therefore, close echocardiography examinations should accompany diazoxide treatment.

Topics: Atrial Natriuretic Factor; Beckwith-Wiedemann Syndrome; Cardiac Catheterization; Congenital Hyperinsulinism; Deprescriptions; Diazoxide; Diuretics; Dose-Response Relationship, Drug; Echocardiography; Electrocardiography; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Male; Natriuretic Peptide, Brain; Sildenafil Citrate; Vasodilator Agents

Chronic fluid overload is common in patients with chronic kidney disease (CKD) and can with time lead to poor prognosis regarding to the cardiovascular events. Serum NT-proBNP and OH/ECW might reflect fluid status of the patients, and the maximal tricuspid regurgitation velocity (TRVmax) could reflect systolic pulmonary artery pressure (SPAP). We investigated the relationship between markers of volume status and marker of pulmonary hypertension (PH) in non-dialysis CKD5 (CKD5-ND) patients.. Bioimpedance spectroscopy (BIS), echocardiography, and measurement of serum NT-proBNP were performed in 137 consecutive patients on the same day. TRVmax greater than or equal to 2.9 m/s, corresponding to SPAP of approximately 36 mmHg, was used as a definition of the possibility of PH in the absence of left heart disease and chronic respiratory disease (PH group).. Patients with possibility of PH (TRVmax ≥ 2.9 m/s) was found in 27 (19.70%) patients. Among the values obtained from BIS, those reflecting the fluid balance (OH, OH/ECW, and E/I ratio) were significantly higher in the PH group. The OH/ECW in patients with PH were significantly higher than those patients without (26.76 ± 15.07 vs. 13.09 ± 15.05, P < 0.001). NT-proBNP was also significantly higher in PH group compared to the non-PH group (median = 10,112 pg/ml, IQR = 30,847 pg/ml vs. median = 1,973 pg/ml, IQR = 7,093 pg/ml, P < 0.001). OH/ECW was positively associated with TRVmax (r = 0.235, P = 0.006). Multivariate logistic regression revealed that increased OH/ECW and serum NT-proBNP were significantly associated with an increased risk of PH.. A significant number of patients showed increased TRVmax, which was closely related to volume status in CKD5-ND patients. Echocardiography and BIS could be important players in a high possibility of PH detection and treatment in asymptomatic CKD patients. Therefore, these measures could be helpful to improve the cardiac outcomes after initiating renal replacement therapy. Further research may be needed to validate the consistency of this association across other stages of CKD.

Topics: Adult; Aged; Biomarkers; Dielectric Spectroscopy; Echocardiography; Female; Humans; Hypertension, Pulmonary; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Water-Electrolyte Balance

In Respiratory Syncytial Virus infection, the early identification of infants at risk for severe disease in order to potentially decrease morbidity could be considered a major goal. Current guidelines recommend only clinical observation for this purpose in infants without known comorbidities. However, recent evidence shows that the presence of pulmonary hypertension in this population is a relevant risk factor for the development of a severe illness, even in healthy infants. The determination of plasmatic NT-proBNP levels could help to identify those cases that benefit of echocardiographic screening to detect pulmonary hypertension in this population during hospitalization.

Topics: Biomarkers; Disease Progression; Echocardiography; Female; Heart Ventricles; Humans; Hypertension, Pulmonary; Infant; Male; Mass Screening; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Respiratory Syncytial Virus Infections; Risk Factors; Severity of Illness Index

Topics: Blood Pressure; Body Mass Index; Guidelines as Topic; Hemodynamics; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Risk

Research comparing bosentan and macitentan in chronic thromboembolic pulmonary hypertension (CTEPH) is scarce, although macitentan might have superior pharmacologic properties. We present the first real-world, 2-year follow-up results and compare clinical outcomes of both drugs in CTEPH.. All consecutive, technical inoperable or residual CTEPH patients receiving bosentan or macitentan, diagnosed in our multidisciplinary team between January 2003 and January 2019, were included. We report and compare survival, clinical worsening (CW), adverse events, WHO FC, NT-proBNP and 6-min walking test (6MWT) until 2 years after medication initiation.. In total, 112 patients receiving bosentan or macitentan (58% female, mean age 62 ± 14 years, 68% WHO FC III/IV, 51% bosentan) could be included. Mean treatment duration was 1.9 ± 0.4 years for bosentan and 1.2 ± 0.6 years for macitentan. Two-year survival rate was 91% for bosentan and 80% for macitentan (HR mortality macitentan 1.85 [0.56-6.10], p = 0.31). Two-year CW-free survival was 81% and 58%, respectively (HR CW macitentan 2.16 [0.962-4.87], p = 0.06). Right atrial pressure, cardiac output (for mortality alone) and 6MWT lowest saturation were multivariate predictors at baseline. Overall adverse event rates were comparable and WHO FC, NT-proBNP and 6MWT distance improved similar for both drugs till 2-year follow-up.. CTEPH patients receiving bosentan or macitentan have improved clinical outcomes till 2-year follow-up, without significant differences in outcomes between both therapies.

Topics: Aged; Bosentan; Chronic Disease; Drug Therapy, Combination; Endarterectomy; Endothelin Receptor Antagonists; Enzyme Activators; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Pulmonary Embolism; Pyrazoles; Pyrimidines; Retrospective Studies; Sildenafil Citrate; Sulfonamides; Survival Rate; Walk Test

Recently, there has been an increasing interest in the potential clinical use of several inflammatory indexes, namely, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic-immune-inflammation index (SII). This study aimed at assessing whether these markers could be early indicators of pulmonary hypertension (PH) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A total of 185 patients were enrolled in our retrospective study from January 2017 to January 2019. Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the clinical significance of these biomarkers to predict PH in patients with AECOPD. According to the diagnostic criterion for PH by Doppler echocardiography, the patients were stratified into two groups. The study group consisted of 101 patients complicated with PH, and the control group had 84 patients. The NLR, PLR, and SII values of the PH group were significantly higher than those of the AECOPD one (

Topics: Aged; Biomarkers; Blood Platelets; Carboxypeptidase B; Disease Progression; Electrocardiography; Female; Humans; Hypertension, Pulmonary; Inflammation; Lymphocytes; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Neutrophils; Peptide Fragments; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive; ROC Curve

There is little information about vitamin D (Vit D) deficiency in patients with pulmonary hypertension (PH). The objective of this study was: 1) compare Vit D levels between patients with PH, left ventricular failure (LVF) and healthy subjects (HS); 2) correlate, in patients with PH, Vit D levels with prognosis-related variables, such as the 6-min walk test (6MWT).. Vitamin D levels were measured in a cross-sectional study in 126 patients from one of three groups: patients with PH (n = 53), patients with LVF (n = 42) and healthy subjects (n = 31). In all groups, 8-h fasting blood samples were obtained in the morning. In the PH and the LVF group, functional class (WHO criteria), metres covered in the 6MWT and echocardiographic parameters were analysed. In the PH group, plasma N terminal pro B type natriuretic peptide (NT-proBNP) level was analysed and a complete haemodynamic evaluation by right heart catheterisation was made.. Mean Vit D levels were lower in PH than in both other groups (ng/ml, mean ± SD): PH 19.25 ± 10, LVF 25.68 ± 12, HS 28.8 ± 12 (PH vs LVF p = 0.017, PH vs HS p = 0.001 and HS vs LVF p = 0.46). Vit D deficiency prevalence was higher in PH as compared to the other groups (PH 53.8%, LVF 45.2%, HS 25%, p = 0.01). Patients with PH in functional class (FC; WHO criteria) III-IV had higher Vit D deficiency prevalence than those in FC I-II (86.7% vs 40.5%, p = 0.003). There was a significant linear correlation between the 6MWT and Vit D levels in PH (p < 0.01), but not in LVF (p = 0.69).. Vit D levels were lower in patients with PH as compared to patients with LVF and HS and correlated directly with 6-min walk distance.

Topics: Adult; Aged; Case-Control Studies; Cross-Sectional Studies; Echocardiography; Female; Heart Failure; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prognosis; Ventricular Dysfunction, Left; Vitamin D; Vitamin D Deficiency; Walk Test; Young Adult

Chronic thromboembolic pulmonary hypertension (CTEPH) can be treated with balloon pulmonary angioplasty (BPA) in inoperable patients. Sensitive non-invasive imaging methods are missing to detect treatment response after a single BPA treatment session. Therefore, the aim of this study was to measure treatment response after a single BPA session using cardio-pulmonary MRI.. Overall, 29 patients with CTEPH were examined with cardio-pulmonary MRI before and 62 days after their initial BPA session. Pulmonary blood flow (PBF), first-pass bolus kinetic parameters, and biventricular mass and function were determined. Multiple linear regression analysis was implemented to estimate the relationship of PBF change in the treated lobe with treatment change of full width at half maximum (FWHM), cardiac output (CO), ventricular mass index (VMI), pulmonary transit time (PTT) and PBF change in the non-treated lobes. Paired Wilcoxon rank sum test and Spearman rho correlation were used.. After BPA regional PBF increased in the treated lobe (p < 0.0001) as well as in non-treated lobes (p = 0.015). PBF treatment changes in the treated lobe were significantly larger compared with the non-treated lobes (p = 0.0049). Change in NT proBNP, MRI-derived mean pulmonary artery pressure (mPAP), PTT, FWHM, right ventricular (RV) ejection fraction, RV stroke volume, CO, VMI and PBF in the non-treated lobes correlated with PBF change in the treated lobe (p < 0.05). PBF changes in the treated lobe were independently predicted by PTT as well as PBF change in the non-treated lobes.. Cardio-pulmonary MRI detects and quantifies treatment response after a single BPA treatment session.. • Two months after BPA regional parenchymal pulmonary perfusion (PBF) increased in the total lung parenchyma (p = 0.005), the treated lobes (p < 0.0001) and non-treated lobes (p = 0.015). • The PBF treatment changes in the treated lobe were significantly larger than in the non-treated lobes (p = 0.0049). • Change in NT proBNP, MRI-derived mean pulmonary artery pressure, pulmonary transit time, full width at half maximum, right ventricular (RV) ejection fraction, RV stroke volume, cardiac output, ventricular mass index and PBF in the non-treated lobes correlated with PBF change in the treated lobe (p < 0.05).

Topics: Aged; Angioplasty, Balloon; Cardiac Output; Female; Humans; Hypertension, Pulmonary; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Pulmonary Circulation; Pulmonary Embolism; Retrospective Studies; Treatment Outcome; Ventricular Function, Right

Pulmonary arterial hypertension (PAH) is more prevalent in females. Paradoxically, female patients have better right ventricular (RV) function and higher survival rates than males. However, the effects of 17β-estradiol (E2) on RV function in PAH has not been studied. Twenty-four male rats were exposed to monocrotaline (MCT) to induce experimental PAH, while treated with E2 or vehicle respectively. Together with eight control rats, thirty-two rats were examined by echocardiography 4 weeks after drug administration. Echocardiographic measurement of RV function included: tricuspid annular plane systolic excursion (TAPSE), RV index of myocardial performance (RIMP), RV fractional area change (RVFAC) and tricuspid annular systolic velocity (s'). RV free wall longitudinal strain (RVLS

Topics: Animals; Biomarkers; Disease Models, Animal; Echocardiography; Estradiol; Fibrosis; Heart Ventricles; Hemodynamics; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Monocrotaline; Natriuretic Peptide, Brain; Rats, Sprague-Dawley; Time Factors; Ventricular Dysfunction, Right; Ventricular Function, Right; Ventricular Remodeling

Prostaglandin E1 (PGE) has been used to maintain ductus arteriosus patency and unload the suprasystemic right ventricle (RV) in neonates with congenital diaphragmatic hernia (CDH) and severe pulmonary hypertension (PH). Here we evaluate the PH response in neonates with CDH and severe PH treated with PGE.. We performed a retrospective chart review of CDH infants treated at our center between 2011 and 2016. In a subset, PGE was initiated for echocardiographic evidence of severe PH, metabolic acidosis, or hypoxemia. To assess PH response, we evaluated laboratory data, including B-type natriuretic peptide (BNP) and echocardiograms before and after PGE treatment. Categorical and continuous data were analyzed with Fisher's exact tests and Mann-Whitney t-tests, respectively.. Fifty-seven infants were treated with PGE a mean 17 ± 2 days. BNP levels declined after 1.4 ± 0.2 days of treatment and again after 5.2 ± 0.6 days. After 6 ± 0.8 days of treatment, echocardiographic estimates of severe PH by tricuspid regurgitation jet velocity, ductus arteriosus direction, and ventricular septum position also improved significantly. Treatment was not associated with postductal hypoxemia or systemic hypoperfusion.. In patients with CDH and severe PH, PGE is well tolerated and associated with improved BNP and echocardiographic indices of PH, suggesting successful unloading of the RV.. Treatment study.. Level III.

Topics: Alprostadil; Echocardiography; Female; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Infant, Newborn; Male; Natriuretic Peptide, Brain; Philadelphia; Registries; Retrospective Studies; Treatment Outcome; Vasodilator Agents

This study aimed to investigate the prognostic value of six different biomarkers in patients with pulmonary hypertension (PH) and to explore whether a multi-biomarker approach can contribute to a better risk stratification.. In this prospective study, patients with PH were included at the day of the diagnostic right heart catheterization between May 2012 and October 2016. Venous blood sampling included; NT-proBNP, high sensitive troponin-T, high sensitive CRP, galectin-3, red blood cell distribution width and eGFR. Associations between biomarker levels and the primary endpoint (death or lung transplantation) and secondary endpoint (death, lung transplantation or heart failure) were assessed with Cox regression, adjusted for age and sex. Additionally, adjustment for the REVEAL risk score was performed.. In total, 106 patients were included (median age 58.7 [IQR 47.0-69.2] years, 64% women, 51% pulmonary arterial hypertension). After a median follow-up duration of 23.9 [IQR 15.1-40.0] months, respectively 29 and 37 patients reached the primary and secondary endpoint. All six biomarkers, except eGFR, were significantly associated with the endpoints. A multi-biomarker approach including the number of elevated biomarkers per patient, demonstrated that patients were at higher risk of adverse events as more biomarker levels were elevated (HR for each extra elevated biomarker; 1.33, 95% CI 1.07-1.64, P = .01). However, a single as well as a combination of multiple biomarkers, did not yield prognostic value independent of the REVEAL risk score.. Various biomarkers are associated with the event-free survival in adults with PH. However, risk stratification exclusively based on single or a combination of biomarkers seems not superior to existing risk scores.

Topics: Adult; Age Factors; Aged; Biomarkers; Blood Proteins; C-Reactive Protein; ErbB Receptors; Erythrocyte Indices; Female; Galectin 3; Galectins; Heart Failure; Humans; Hypertension, Pulmonary; Lung Transplantation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Progression-Free Survival; Proportional Hazards Models; Prospective Studies; Sex Factors; Troponin T

Topics: Animals; Atrial Natriuretic Factor; Benzoxazoles; Cell Hypoxia; Cell Line; Disease Models, Animal; Drugs, Chinese Herbal; Hemeproteins; Hypertension, Pulmonary; Male; Myocytes, Cardiac; NADPH Oxidase 2; NADPH Oxidase 4; NADPH Oxidases; Natriuretic Peptide, Brain; Peroxidases; Rats, Sprague-Dawley; Salvia miltiorrhiza; Triazoles; Ventricular Remodeling

Red cell width distribution (RDW) is known to be a prognostic marker in adults with pulmonary hypertension. The value of this test in the pulmonary arterial hypertension (PAH) pediatric population was not yet established. The aim of the study was to evaluate the prognostic value of RDW in children with PAH and utility of this parameter in the management. Data were collected retrospectively in 61 patients with PAH confirmed by right heart catheterization. RDW was measured at diagnosis, 3 and 12 months after initial therapy, during and after deterioration if occurred. Results were compared with NTproBNP, WHO-FC and oxygen blood saturation. Mean RDW at baseline was 15.3 ± 2.4% (12.1-24.4, median 14.7%) and was elevated in 29 patients (47%). There were no significant difference in clinical status, NTproBNP and hemodynamic parameters among patient with normal and elevated RDW at diagnosis. Poor negative correlation with SaO

Topics: Biomarkers; Cardiac Catheterization; Child; Child, Preschool; Erythrocyte Indices; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies

Background Obesity is a precursor to heart failure with preserved ejection fraction. Biomarkers that identify preclinical metabolic heart disease ( MHD ) in young obese patients would help identify high-risk individuals for heart failure prevention strategies. We assessed the predictive value of GAL3 (galectin-3), FSTL3 (follistatin-like 3 peptide), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) to identify stage B MHD in young obese participants free of clinically evident cardiovascular disease. Methods and Results Asymptomatic obese patients (n=250) and non-obese controls (n=21) underwent echocardiographic cardiac phenotyping. Obese patients were classified as MHD positive ( MHD - POS ; n=94) if they had abnormal diastolic function or left ventricular hypertrophy and had estimated pulmonary artery systolic pressure ≥35 mm Hg. Obese patients without such abnormalities were classified as MHD negative (MHD-NEG; n=52). Serum biomarkers timed with echocardiography. MHD - POS and MHD-NEG individuals were similarly obese, but MHD - POS patients were older, with more diabetes mellitus and metabolic syndrome. Right ventricular coupling was worse in MHD - POS patients ( P<0.001). GAL 3 levels were higher in MHD - POS versus MHD -NEG patients (7.7±2.3 versus 6.3±1.9 ng/mL, respectively; P<0.001). Both GAL 3 and FSTL 3 levels correlated with diastolic dysfunction and increased pulmonary artery systolic pressure but not with left ventricular mass. In multivariate models including all 3 biomarkers, only GAL 3 remained associated with MHD (odds ratio: 1.30; 95% CI , 1.01-1.68; P=0.04). Conclusions In young obese individuals without known cardiovascular disease, GAL 3 is associated with the presence of preclinical MHD . GAL 3 may be useful in screening for preclinical MHD and identifying individuals with increased risk of progression to obesity-related heart failure with preserved ejection fraction.

Topics: Adult; Biomarkers; Blood Proteins; Case-Control Studies; Echocardiography; Female; Follistatin-Related Proteins; Galectin 3; Galectins; Heart Failure; Hemodynamics; Humans; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Male; Metabolic Diseases; Middle Aged; Natriuretic Peptide, Brain; Obesity; Peptide Fragments

Through this study, we aimed to assess the ability of routine neonatal screening at time of bronchopulmonary dysplasia (BPD) diagnosis to predict the development of late pulmonary hypertension (PHTN). This is a retrospective longitudinal cohort study of 37 premature infants with BPD assessing the utility of screening serum brain natriuretic peptide (BNP) and echocardiograms performed at the time of BPD diagnosis ('early PHTN') to predict 'late PHTN' at the last follow-up. Screening evaluation demonstrated early PHTN in 9/37 patients. At an average follow-up interval of 52.7 ± 38.7 weeks, 4/9 had late PHTN; one patient without early PHT had late PHT. At initial screening, infants with late PHTN were significantly more likely to have demonstrated elevated BNP values (p = 0.003), and echocardiographic evidence of right atrial dilatation (p = 0.01), right ventricular hypertrophy (p = 0.01), lower right ventricular area change percentage (p = 0.03), and larger main pulmonary artery Z-scores (p = 0.02). Serum BNP and echocardiographic evaluation performed at the time of BPD diagnosis can detect patients at increased risk of late PHTN. Large, prospective studies are necessary to further address this question.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Case-Control Studies; Echocardiography; Female; Gestational Age; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Infant, Premature; Longitudinal Studies; Male; Natriuretic Peptide, Brain; Neonatal Screening; Prospective Studies; Retrospective Studies

This study sought to determine the prevalence, predictors, prognostic relevance and evolution of pulmonary hypertension (PH) (mean pulmonary artery pressure ≥25 mm Hg) in adult patients with a subaortic right ventricle (RV) in a biventricular circulation (2V-RV).. We analysed retrospective data from patients with 2V-RV undergoing cardiac catheterisation in our centre between 2000 and 2018. Echocardiographic assessment of subpulmonary ventricular pressures (left ventricular systolic pressure (LVSP)), age and B-type natriuretic peptide (BNP) were assessed as PH screening tools. Kaplan-Meier curves examined time to a composite outcome of death, transplant or ventricular assist device (VAD). Data from repeat catheterisations were analysed to evaluate PH changes over time, including the effects of therapy.. A total of 141 patients (median age 39 (IQR 33-45) years, 68% men) underwent 191 cardiac catheterisations. At baseline, 55% had PH (isolated postcapillary 24%, combined precapillary and postcapillary 26% and precapillary 5%). BNP (area under the curve 0.80; 95% CI 0.72 to 0.88; p<0.0001), but not age at catheterisation or echocardiographic estimates of LVSP were associated with the presence of PH. The absence of PH and BNP <100 pg/mL discriminated a subgroup at very low risk during short-term (2.5 (1.3-3.9) years) follow-up (p<0.0001). Diuretics, milrinone and VAD improved haemodynamics over time.. PH is prevalent in patients with 2V-RV even when asymptomatic. It is difficult to identify by echocardiography and most importantly, is strongly associated with adverse outcomes. PH affects prognosis and transplant options for this patient group and yet is often amenable to treatment. Awareness of these results ought to lower the threshold for invasive haemodynamic assessment and may change the management of failing patients with 2V-RV.

Topics: Adult; Cardiac Catheterization; Echocardiography; Female; Heart Transplantation; Heart Ventricles; Heart-Assist Devices; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Prevalence; Retrospective Studies; Tricuspid Valve Insufficiency; Ventricular Dysfunction, Left

The demographic characteristics, ratio of aetiologies and biochemical parameters of adult patients with pulmonary hypertension (PH) living in plain and high-altitude regions were investigated and analysed.. In total, 2846 adult patients with PH hospitalized from 2010 to 2015 in the Second Xiangya Hospital of Central South University and Qinghai Red Cross Hospital were retrospectively investigated.. (1) In the present study, the numbers of patients with PH in both the plain and high-altitude regions increased annually (P < 0.05), and the in-hospital prevalence of PH significantly increased over time in the high-altitude region. PH was more common in women in the plain region. Furthermore, compared with PH patients living in the plain region, those living in the high-altitude region were older (P < 0.05) and had higher smoking rates (P < 0.05). In the plain region, the greatest proportion of patients with PH belonged to group 2 (PH because of left heart disease), while in the high-altitude region, group 3 (PH because of lung diseases and/or hypoxia) was the most common (P < 0.05). (2) Haemoglobin levels, red blood cell counts, mean platelet volumes and platelet volume distribution widths were lower in PH patients living in the plain region than in those living in the high-altitude region. Furthermore, platelet counts were higher in patients living in the plain region than in those living in the high-altitude region (P < 0.05). The BNP/NT-proBNP levels were higher in PH patients living in the plain region (45.5%), which were mostly in group 4, than in those living the high-altitude region (P < 0.05).. The data from the hospitals in both the plain and high-altitude regions show a tendency towards increased in-hospital prevalence of PH over the last 6 years. The most common aetiologies of PH in patients living in the plain region and high-altitude regions were left heart disease and lung disease, respectively. Compared with PH patients living in the plain region, those living in the high-altitude region had better cardiac function and less severe PH.

Topics: Adult; Aged; Aged, 80 and over; Altitude; Female; Heart Diseases; Hospitalization; Humans; Hypertension, Pulmonary; Hypoxia; Lung Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Platelet Count; Prevalence; Retrospective Studies; Severity of Illness Index; Smoking; Time Factors

Premature infants with severe bronchopulmonary dysplasia (sBPD) are at risk of pulmonary hypertension (PH). Serum brain natriuretic peptide (BNP) is used to predict disease severity in adult PH. Its diagnostic utility in sBPD-associated PH is unknown.. The aim of this paper was to determine the accuracy of BNP, against echocardiogram (echo), to diagnose PH in infants born <32 weeks' gestation with sBPD.. We conducted a retrospective cohort study of all infants with sBPD with an echo and BNP within a 24-h period, at ≥36 weeks postmenstrual age. PH was defined as: right ventricular pressure >½ systemic blood pressure estimated from tricuspid regurgitant jet or patent ductus arteriosus (PDA) velocity, bidirectional or right-to left-PDA, and/or flat/bowing ventricular septum at end-systole. Receiver-operating characteristic (ROC) curves were constructed to test the diagnostic accuracy of BNP.. Of 128 infants, 68 (53%) had echo evidence of PH. BNP was higher among the infants with PH (median [interquartile range]: 127 pg/mL [39-290] vs. 35 [20-76], p < 0.001). The area under the ROC curve for diagnosing PH using BNP was 0.74 (95% CI 0.66-0.83). At an optimal cutpoint of 130 pg/mL, BNP correctly classified the presence or absence of PH in 70% of the infants (specificity: 92, sensitivity: 50%).. BNP, relative to concurrent echo, demonstrated moderate accuracy for diagnosing PH in this cohort of preterm infants with sBPD. BNP may help rule in PH in this population but has low utility to rule out the disease.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Echocardiography; Gestational Age; Heart Ventricles; Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Natriuretic Peptide, Brain; Retrospective Studies; ROC Curve

To analyze the risk factors for complications in pregnancy associated with pulmonary hypertension (PH) and to develop a logistic regression model to predict cardiac outcomes.. A retrospective analysis was performed on 249 women with PH, who were followed at the Beijing Anzhen Hospital, Affiliated to the Capital Medical University, from January 2012 to March 2015. All pregnancies were recorded. Overall, 214 cases of pulmonary arterial hypertension were identified. Univariate analysis and multivariate analysis were performed to determine the risk factors occurring during or after pregnancy in women with PH. Ultimately, six independent risk factors for cardiac events were determined.. There were 70 cases of cardiac complications (28.1%) with PH, including 7 cases of maternal death (2.81%). Independent risk factors were rapid progression of symptoms [OR=3.044, 95%CI (1.042-8.895), P<0.05], brain natriuretic peptide (BNP) plasma levels ≥300pg/mL [OR=5.543, 95%CI (1.403-21.896), P<0.05], severe pulmonary hypertension (PAP≥80mmHg, 1mmHg=0.133kPa) [OR=6.769, 95%CI (2.748-16.677), P<0.05], World Health Organization functional class (WHO-FC) III-IV [OR=6.053, 95%CI (2.638-13.886), P<0.05], PH pre-pregnancy [OR=5.434, 95%CI (1.298-22.738), P<0.05], and delivery ≥28weeks gestation [OR=10.876, 95%CI (3.957-29.893), P<0.05].. Early advice on contraception for patients with PH, and the need for patients to undergo a comprehensive assessment of cardiac function pre-pregnancy are suggested from the results of the present study.

Topics: Adult; Biomarkers; Chi-Square Distribution; China; Disease Progression; Female; Gestational Age; Heart Diseases; Humans; Hypertension, Pulmonary; Logistic Models; Maternal Death; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Cardiovascular; Premature Birth; Prognosis; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors

Whether non-invasive electrocardiographic parameters may be of similar relevance in pulmonary arterial hy-pertension (PAH) as in left ventricular heart failure (LVHF) remains unclear.. To examine a profile of electrocardiographic parameters in PAH and to determine their prognostic significance. Com-parison of profile in patients with pulmonary hypertension secondary to left ventricular dysfunction was planned in order to put PAH group results into context.. We included 41 patients with type 1.1/1.4.4 (according to the European Society of Cardiology) PAH and 31 patients with LVHF and type 2.1 pulmonary hypertension. All patients underwent 24-h ambulatory electrocardiography monitoring.. Among heart rate variability parameters, only RMSSD was different (mean, 75 ms [PAH] vs. 112 ms [LVHF], p = 0.016). In PAH, fewer patients had ventricular tachycardia (15% vs. 48%, p = 0.004), abnormal deceleration capacity (54% vs. 84%, p = 0.011), positive heart rate turbulence (11% vs. 48%, p = 0.003), severe autonomic failure (10% vs. 39%, p = 0.005), and ventricular late potentials (LP) (19% vs. 62%, p = 0.001). In PAH, four deaths occurred in 42 months. In univariate analysis, the risk factors for death were: LP (hazard ratio 13.55, 95% confidence interval 1.41-130.72; p = 0.024), age, N-terminal prohormone of B-type natriuretic peptide, while the protective factors were minimal and mean heart rate, as well as the six-minute walk test (6MWT) distance. In multivariate analysis, the influence of LP and the 6MWT distance remained significant.. Ventricular LP were present in 19% of PAH patients and were the most powerful risk factor of mortality .

Topics: Adult; Aged; Electrocardiography, Ambulatory; Female; Heart Failure; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Risk Factors; Tachycardia, Ventricular; Ventricular Dysfunction, Left

While the N-terminal pro-brain-type natriuretic peptide (NT-proBNP) at rest is known to be associated with prognosis in pulmonary arterial hypertension (PAH), it is unclear if the NT-proBNP response to exercise (ΔNT-proBNP) can contribute to a better assessment of disease severity.. We investigated the association of NT-proBNP values at rest and during peak exercise with hemodynamics and cardiopulmonary exercise testing parameters in 63 therapy-naive PAH patients.. The median NT-proBNP increases from 1414 at rest to 1500 pg/ml at peak exercise. The ΔNT-proBNP is baseline-dependent in PAH. Both, NT-proBNP at rest and NT-proBNP at peak exercise, are significantly correlated with hemodynamics and functional capacity. However, neither NT-proBNP at peak exercise nor ΔNT-proBNP correlated better with surrogate markers of disease severity than NT-proBNP at rest.. The ΔNT-proBNP does not contribute to a better assessment of disease severity in PAH.

Topics: Aged; Biomarkers; Cohort Studies; Exercise; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Severity of Illness Index

To analyze the role of sensitive cardiac troponin I (scTnI) and high-sensitive troponin T (hscTnT) in the determination of myocardial injury caused by volume and pressure load due to pulmonary hypertension (PH) and to investigate if these markers may be useful in the management of PH in childhood. Twenty-eight patients with congenital heart disease (CHD) with left to right shunt and PH, 29 patients with CHD with left to right shunt but without PH, and 18 healthy children, in total 75 individuals, were included in the study. All cases were aged between 4 and 36 months. Echocardiographic evaluation was performed in all cases, and invasive hemodynamic investigation was performed in 33 cases. Blood samples were obtained from all cases, for the measurement of brain natriuretic peptide (BNP), pro-brain natriuretic peptide (pro-BNP), sensitive cardiac troponin I (scTnI), and high-sensitive troponin T (hscTnT) levels. The mean BNP, pro-BNP, scTnI, and hsTnT levels were statistically significantly higher in patients with PH than in the patients without PH (p < 0.001). A statistically significant positive correlation was determined between pulmonary artery systolic pressure and scTnI and hscTnT levels (r = 0.34 p = 0.01, r = 0.46 p < 0.001, respectively) levels. Pulmonary hypertension determined in congenital heart diseases triggers myocardial damage independently of increased volume or pressure load and resistance, occurring by disrupting the perfusion via increasing ventricular wall tension and the myocardial oxygen requirement. Serum scTnI and hscTnT levels may be helpful markers to determine the damage associated with PH in childhood.

Topics: Angiography; Biomarkers; Child, Preschool; Echocardiography; Female; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Infant; Male; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Sensitivity and Specificity; Troponin I; Troponin T

Plasma brain natriuretic peptide (BNP) level is a prognostic biomarker in pulmonary arterial hypertension (PAH). Its impact on long-term overall survival (OS) was investigated in the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL), a 5-year observational, multicenter, US registry of patients with PAH.. Patients were ≥ 18 years of age, met right heart catheterization criteria at rest, had World Health Organization group I PAH, and had BNP measurement at enrollment. Optimal BNP threshold was obtained via receiver operating characteristic curve analysis. OS was compared in patients with low (≤ 340 pg/mL) vs high (> 340 pg/mL) BNP at baseline; changes between baseline and last assessment were also examined. Patients were categorized based on baseline (low or high) and follow-up (low or high) BNP values; hazard ratios (HRs) for OS were estimated and compared using Cox regression.. Overall, 1,426 patients were analyzed. Mortality risk was significantly higher in patients with baseline high vs low BNP (HR, 3.6; 95% CI, 3.0-4.2). BNP change analysis at ≤ 1 year postenrollment demonstrated that the low-low group had the lowest and the high-high group had the highest 5-year mortality risk (HR, 0.23; 95% CI, 0.19-0.27). Changes in BNP score also correlated with change of risk of death.. Baseline BNP threshold of 340 pg/mL strongly predicted survival up to 5 years in patients with PAH. A BNP reduction at 1 year since enrollment was associated with decreased mortality risk, whereas an increase in BNP at 1 year was associated with an increased mortality risk, supporting BNP as a surrogate marker of PAH survival.

Topics: Biomarkers; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Pulmonary Wedge Pressure; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Survival Rate; Time Factors; United States

To assess the efficacy and safety of subcutaneous treprostinil in adult patients with congenital heart disease (CHD)-associated pulmonary arterial hypertension (PAH) after 12 months of treatment.. Consecutive adult patients with CHD-PAH received subcutaneous treprostinil to maximum tolerated doses in an observational study.. Advanced CHD-PAH patients with WHO class III or IV disease (n=32, age 40±10 years, 20 females) received treprostinil for suboptimal response to bosentan (n=12), WHO functional class IV disease (FC, n=7) or prior to bosentan approval (n=13). In the multivariate mixed model, mean increase in 6 min walk distance (6-MWD) from baseline to 12 months was 114 m (76; 152) (P<0.001). WHO FC improved significantly (P=0.001) and B-type brain natriuretic peptide decreased from 1259 (375; 2368) pg/mL to 380 (144; 1468) pg/mL (P=0.02). In those 14 patients who had haemodynamic data before and after initiation of treprostinil, pulmonary vascular resistance decreased significantly (from 18.4±11.1 to 12.6±7.9 Wood units, P=0.003). The most common adverse events were infusion-site erythema and pain. One patient stopped treatment because of intolerable infusion-site pain after 8 months of treatment. No other major treatment-related complications were observed. Five patients died during early follow-up, having experienced a decrease in their 6-MWD prior.. Subcutaneous treprostinil therapy is generally safe and effective for at least 12 months and may be used in CHD-related PAH class III and IV.

Topics: Adult; Antihypertensive Agents; Cohort Studies; Epoprostenol; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Infusion Pumps; Infusions, Subcutaneous; Male; Natriuretic Peptide, Brain; Oxygen; Vascular Resistance; Walk Test

To identify circulating angiogenic and inflammatory biomarkers with potential in screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc), and in early diagnosis and determination of treatment response in PAH.. Plasma samples were taken at the time of PAH diagnosis and at treatment follow-up after a median (interquartile range) of 4 months (3-9.8 months) in idiopathic (n = 9) and SSc-associated PAH (n = 11). In patients with SSc-associated PAH, plasma samples had also been gathered a median of 2 years (0.8-3 years) before PAH diagnosis (n = 10). Additional plasma samples were retrieved at two time-points separated by a median of 12 years (10-13 years) from SSc patients who did not develop PAH (n = 10) and from controls (n = 8). Angiogenic and inflammatory biomarkers were analysed by multiplex immunoassays.. Plasma levels of placenta growth factor (PlGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), and tumour necrosis factor-α (TNF-α) were higher (p < 0.05) in SSc patients who later developed PAH than in those who did not. Plasma vascular endothelial growth factor (VEGF)-D increased (p < 0.05) in SSc patients as PAH developed. Plasma levels of PlGF, VEGF-A, VEGF-D, sVEGFR-1, interleukin-6, and TNF-α were higher (p < 0.05) in PAH than controls. There were no significant differences in circulating biomarkers between idiopathic and SSc-associated PAH. Plasma sVEGFR-1 decreased (p < 0.05) after initiating PAH-targeted treatments.. Plasma levels of PlGF, sVEGFR-1, TNF-α, and VEGF-D have potential in screening for SSc-associated PAH. Plasma sVEGFR-1 may be a biomarker of treatment response.

Topics: Aftercare; Aged; Biomarkers; Case-Control Studies; Female; Humans; Hypertension, Pulmonary; Inflammation; Interleukin-6; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Neovascularization, Pathologic; Peptide Fragments; Placenta Growth Factor; Scleroderma, Systemic; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor D; Vascular Endothelial Growth Factor Receptor-1; Vascular Resistance; Walk Test

Plasma pro-BNP (brain natriuretic peptide) levels are often elevated in response to right ventricular (RV) volume and pressure overload, parameters potentially affected by exercise. Plasma pro-BNP levels change in association with long-term changes in pulmonary hemodynamics, thereby serving as a potential biomarker in pulmonary arterial hypertension (PAH). The 6-min Walk Test (6MWT) and pro-BNP level are often checked in a single office visit. There is no universal standard for measuring Pro-BNP levels relative to the timing of the 6MWT. Based on the studies in normal subjects indicating that pro-BNP levels changes after exercise, we hypothesized that the pro-BNP might rise after the 6MWT in PAH patients, potentially impacting clinical decisions.. Patients at our center with WHO Group 1 PAH on active therapy at a stable dose for 30 days or more were enrolled. After resting the patient for 30 min, blood was drawn for baseline pro-BNP and a 6MWT was performed. Pro-BNP levels were drawn immediately after the 6MWT and 1 and 2 h later. Pro-BNP was measured using a commercially available ELISA kit. The levels before exercise and after exercise were compared using student's paired t tests.. There were 17 females and 3 male subjects. The mean age was 53 ± 11 years. Seven patients had systemic lupus erythematosus-related PAH, six had idiopathic PAH, three had scleroderma, three had portopulmonary hypertension, and one had HIV-related PAH. The mean PA pressure was 50 ± 15 mmHg with a mean pulmonary vascular resistance of 10 ± 4 Wood units. The majority of the patients were on multimodality PAH therapy, including parenteral prostacyclins. Mean 6MWT distance was 377 ± 140 m. In 14/20 patients, the pro-BNP level increased immediately after the 6MWT; in 12/20 patients, the pro-BNP level was elevated at 1 h post exercise. In the majority of the patients, the pro-BNP fell to baseline 2 h post 6MWT.. There appears to be a trend of pro-BNP level increasing immediately after exercise and continuing to be elevated at 1 h. Pro-BNP levels then return to baseline at 2 h post 6MWT.

Topics: Adult; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Time Factors; Walk Test

The latest pulmonary hypertension (PH) guidelines define therapeutic goals in terms of symptoms, exercise capacity, and haemodynamics for patients with pulmonary arterial hypertension (PAH) and recommend advanced combined medical therapy. For inoperable or post-surgical residual distal chronic thromboembolic PH (CTEPH) medical treatment is similarly advised.. We analysed whether risk factor goals are achieved and combination therapy is used in prevalent patients with PAH or distal CTEPH.. PAH or distal CTEPH patients who were seen at the University Hospital Zurich during the last year were analysed in terms of demography, clinical data, medication, and therapeutic goals. Achievement of therapeutic goals was defined as New York Heart Association (NYHA) class ≤II, N-terminal pro-brain natriuretic peptide (NTpro-BNP) < 300 ng/L, and 6-min walking distance (6MWD) > 440 m.. A total of 108 PAH patients (age 59 ± 18 years, 62% female, 64% idiopathic, 36% associated) and 38 distal CTEPH patients (age 69 ± 14 years, 55% female) were included. They had been diagnosed on average 66 ± 48 months (±SD) previously. The percentage of PAH/CTEPH patients with NYHA ≤II was 52/53, respectfully, the percentage of those with NTproBNP < 300 ng/L was 61/52, and with 6MWD > 440 m 63/50. Overall, 33/31% fulfilled 3 and 29/35% fulfilled 2 of these goals. Regarding therapy, 43% of PAH patients were on double and 10% on triple combination therapy, whereas 16% of distal CTEPH patients were on double and 3% on triple combination therapy.. In this real-life cohort of prevalent patients with PAH or distal CTEPH, targeted drug therapy resulted in an achievement of ≥2/3 predefined therapeutic goals in 2/3 of patients. Patients with PAH were more likely to receive combination therapy compared to CTEPH patients.

Topics: Adult; Aged; Antihypertensive Agents; Body Mass Index; Chronic Disease; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Thromboembolism; Treatment Outcome; Walk Test

Continuous intravenous epoprostenol was the first treatment approved for pulmonary arterial hypertension (PAH) but administration through a central venous line carries risks of thrombosis and sepsis, particularly in children. We sought to evaluate the safety, efficacy and management of subcutaneous (SC) treprostinil in children with PAH.. Fifty-six children (median age 65, range 1-200 months) were treated with SC treprostinil. Clinical status, echocardiography, NT-proBNP, and site pain and infection were evaluated. Right heart catheterization was performed in 54 patients before starting SC treprostinil infusion and was repeated at 6 months in 31 patients.. Treatment was well tolerated in 79% of patients. Site pain resistant to simple analgesics occurred in 12 patients (21%), but could be managed in 9/12 children. At 6 months, 3 patients had died, 4 had received a Potts shunt and 1 underwent lung transplantation. Among the 48 treated patients, 40 (83%) showed significant improvement in WHO functional class, 6 minute walk distance, NT-proBNP and pulmonary vascular resistance (p < 0.01 for all parameters). At last follow-up (median 37 months), ten patients had died, 2 underwent a lung transplantation and 8 underwent a Potts shunt. In 30 of the 36 remaining treated patients, improvement of clinical status was sustained. No children developed sepsis and 12 had minor site infections.. Subcutaneous treprostinil infusion is an effective therapy without serious side effects in children with PAH. Site pain can be managed with simple analgesics in most children.

Topics: Adolescent; Analgesics; Antihypertensive Agents; Cardiac Catheterization; Child; Child, Preschool; Cohort Studies; Echocardiography; Epoprostenol; Female; France; Humans; Hypertension, Pulmonary; Infant; Infusions, Subcutaneous; Male; Natriuretic Peptide, Brain; Pain, Procedural; Peptide Fragments; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Severe portopulmonary hypertension (POPH) is a contraindication for liver transplantation (LT) because of the high risk of postoperative heart failure. The early detection of POPH is important for patients with biliary atresia (BA). Brain natriuretic peptide (BNP) is known to be correlated with liver fibrosis in patients with liver cirrhosis. The aim of this study was to elucidate the efficacy of BNP measurement for the follow-up of patients with BA. Thirty-two patients with BA were identified from September 2011 to December 2016. As indices of liver fibrosis/cirrhosis, APRI (P < .0001), FIB-4 (P < .0001), Child-Pugh score (P < .0001), IV collagen (P = .0005), and hyaluronic acid (P = .0291) had high or moderate correlations with BNP. Patients with splenomegaly, esophageal varices, liver fibrosis, and collateral veins had significantly higher BNP levels than those without. Patients diagnosed with POPH had significantly higher BNP levels in comparison with those patients without (P = .0068). In contrast, PELD/MELD scores showed an almost negligible correlation with the BNP level. LT was successful in 3 asymptomatic BA patients with POPH who had high BNP levels despite the low PELD/MELD scores. In conclusion, routine serum BNP surveillance can be easy to predict asymptomatic POPH. This may help to identify POPH before it reaches a stage that would contraindicate LT.

Topics: Adolescent; Adult; Asymptomatic Diseases; Biliary Atresia; Biomarkers; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Hypertension, Portal; Hypertension, Pulmonary; Liver Transplantation; Male; Natriuretic Peptide, Brain; Retrospective Studies; Young Adult

N-terminal-probrain natriuretic peptide (NT-proBNP) is a marker of hemodynamically significant patent ductus arteriosus (HsPDA) in preterm infants. In this study, we assessed whether NT-proBNP levels could predict the risk of moderate to severe bronchopulmonary dysplasia (BPD) and/or death.. This was an observational prospective study of preterm infants with GA ≤32 weeks. Infants who died within the first 48 h or who had major congenital malformations or incomplete information were excluded. NT-proBNP was determined at 48-96 h of life and at 5-10 days of life. The predictive capacity of NT-proBNP for the combined outcome of BPD and/or death was evaluated using receiver operator characteristic (ROC) curves and multivariate regression.. Of the 125 eligible patients, 110 completed the analysis. Twenty-eight developed BPD (n = 15) and/or died (n = 13). Infants who developed BPD and/or died had higher NT-proBNP levels ​​at 48-96 h (26,848 ng/L, interquartile range [IQR] 7818-60,684 vs 3008 ng/L, IQR 1425-9876) and at 5-10 days (8849 ng/L, IQR 3796-19,526 vs 1427 ng/L, IQR 907-2889). The NT-proBNP levels at 5-10 days, but not at 48-96 h, were independently associated with BPD and/or death after adjustments for HsPDA and other confounders (OR = 3.36; 95%CI: 1.52-7.4, P = 0.006). For the prediction of this result, a cutoff of 3348 ng/L had a sensitivity and specificity of 82% and 83%, respectively (area under the curve [AUC] = 0.87; 95%CI: 0.79-0.95).. The NT-proBNP levels at 5-10 days of life may identify preterm infants with an HsPDA who are at high risk of BPD or death and may be useful for individualized preventive and therapeutic strategies.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Enterocolitis, Necrotizing; Female; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Intracranial Hemorrhages; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Respiratory Insufficiency; Sensitivity and Specificity; Sepsis

In pulmonary hypertension (PH), both wedge pressure elevation (PAWP) and a precapillary component may affect right ventricular (RV) afterload. These changes may contribute to RV failure and prognosis. We aimed at describing the different haemodynamic phenotypes of patients with PH due to left heart disease (LHD) and at characterizing the impact of pulmonary haemodynamics on RV function and outcome PH-LHD.. Patients with PH-LHD were compared with treatment-naïve idiopathic/heritable pulmonary arterial hypertension (PAH, n = 35). PH-LHD patients were subdivided in Isolated post-capillary PH (IpcPH: diastolic pressure gradient, DPG<7 mmHg and pulmonary vascular resistance, PVR≤3 WU, n = 37), Combined post- and pre-capillary PH (CpcPH: DPG≥7 mmHg and PVR>3 WU, n = 27), and "intermediate" PH-LHD (either DPG <7 mmHg or PVR ≤3 WU, n = 29).. Despite similar PAWP and cardiac index, haemodynamic severity and prevalence of RV dysfunction increased from IpcPH, to "intermediate" and CpcPH. PVR and DPG (but not compliance, Ca) were linearly correlated with RV dysfunction. CpcPH had worse prognosis (p<0.05) than IpcPH and PAH, but similar to "intermediate" patients. Only NTproBNP and Ca independently predicted survival in PH-LHD.. In PH-LHD, haemodynamic characterization according to DPG and PVR provides important information on disease severity, predisposition to RV failure and prognosis. Patients presenting the CpcPH phenotype appear to have haemodynamic profile closer to PAH but with worse prognosis. In PH-LHD, Ca and NTproBNP were independent predictors of survival.

Topics: Adult; Aged; Biomarkers; Calcium; Capillaries; Cardiac Catheterization; Endothelium, Vascular; Female; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Phenotype; Proportional Hazards Models; Pulmonary Wedge Pressure; Retrospective Studies; Treatment Outcome; Vascular Resistance; Vasoconstriction; Ventricular Dysfunction, Left

Pulmonary hypertension (PH) is a known complication of bronchopulmonary dysplasia (BPD). This study aimed to determine the utility of serial N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) levels in the screening of BPD associated PH (BPD-PH) in preterm infants.. Infants with birth weight <1500 g and <30 week corrected gestational age (CGA) were followed with serial NTproBNP levels and echocardiograms (ECHO). They were divided into control, BPD and BPD-PH groups. Statistical analyses included repeated measures analysis of variance and receiver operator curve (ROC) generation.. Infants in the BPD-PH and BPD group had significantly elevated NTproBNP levels as compared to the control group. ROC curves for NTproBNP at 28 weeks CGA provided a cut-point of 2329 pg/ml and 578.1 pg/ml for detection of BPD-PH and BPD, respectively.. NTproBNP appears to be a good screening tool to determine the onset of BPD-PH as early as 28 weeks CGA.

Topics: Biomarkers; Birth Weight; Bronchopulmonary Dysplasia; Echocardiography; Female; Gestational Age; Humans; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Linear Models; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; ROC Curve

Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration is elevated in patients with pulmonary hypertension (PH); however, its role in the detection of PH associated with lung disease is not well established.. The aim of this study was to assess the value of NT-proBNP in the detection of PH in patients with end-stage lung disease (esLD) referred for lung transplantation.. The study population consisted of 65 patients: 37 with idiopathic pulmonary fibrosis (IPF), 20 with chronic obstructive pulmonary disease, and 8 patients with other interstitial lung diseases (75% men, mean age 53.3 ± 9.5 years). Serum concentration of NT-proBNP was assessed with an immunoradiometric assay kit. The mean pulmonary artery pressure (mPAP) was measured using a Swan-Ganz catheter. PH was defined as mPAP ≥ 25 mm Hg.. Median NT-proBNP concentrations were significantly higher in patients with PH than in patients without PH: 139 (49-1236) pg/mL vs 67 (38-116) pg/mL, respectively; P = .016. Receiver operating characteristic (ROC) analysis revealed that NT-proBNP concentration higher than 131.5 pg/mL was a predictor of PH with good specificity (81%) and positive predictive value (78.9%) but low sensitivity (55.6%) and negative predictive value (58.6%). The area under the ROC curve of serum NT-proBNP concentration for PH was 0.71 (95% confidence interval 0.57-0.85, P = .039).. Serum concentration of NT-proBNP may be useful in the diagnosis of PH in patients with esLD referred for lung transplantation.

Topics: Adult; Aged; Biomarkers; Female; Humans; Hypertension, Pulmonary; Lung Diseases; Lung Transplantation; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Sensitivity and Specificity

Balloon pulmonary angioplasty (BPA) is an interventional treatment modality for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Therapy monitoring, based on non-invasive biomarkers, is a clinical challenge. This post-hoc study aimed to assess dynamics of high-sensitivity cardiac troponin T (hs-cTnT) as a marker for myocardial damage and its relation to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels as a marker for cardiac wall stress.. This study included 51 consecutive patients who underwent BPA treatment and completed a 6-month follow-up (6-MFU) between 3/2014 and 3/2017. Biomarker measurement was performed consecutively prior to each BPA and at 6-MFU. In total, the 51 patients underwent an average of 5 BPA procedures. The 6-month survival rate was 96.1%. The baseline (BL) meanPAP (39.5±12.1mmHg) and PVR (515.8±219.2dyn×sec×cm-5) decreased significantly within the 6-MFU (meanPAP: 32.6±12.6mmHg, P<0.001; PVR: 396.9±182.6dyn×sec×cm-5, P<0.001). At BL, the median hs-cTnT level was 11 (IQR 6-16) ng/L and the median NT-proBNP level was 820 (IQR 153-1872) ng/L. The levels of both biomarkers decreased steadily after every BPA, showing the first significant difference after the first procedure. Within the 6-MFU, hs-cTnT levels (7 [IQR 5-12] ng/L; P<0.001) and NT-proBNP levels (159 [IQR 84-464] ng/l; P<0.001) continued to decrease. The hs-cTnT levels correlated with the PVR (rrs = 0.42; p = 0.005), the meanPAP (rrs = 0.32; p = 0.029) and the NT-proBNP (rrs = 0.51; p<0.001) levels at BL.. Non-invasive biomarker measurement provides valuable evidence for the decreasing impairment of myocardial function and structure during BPA therapy. Changes in hs-cTNT levels are suggestive for a reduction in ongoing myocardial damage.

Topics: Aged; Angioplasty, Balloon; Biomarkers; Chronic Disease; Female; Humans; Hypertension, Pulmonary; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Circulation; Pulmonary Embolism; Treatment Outcome; Troponin T

Risk assessment of pulmonary arterial hypertension (PAH) contributes to its management. Unfortunately, the existing risk assessment approaches are defective for clinicians to practice in daily clinical settings to some extent.. We designed a modified Risk Assessment Score of PAH (mRASP) comprising four non-invasive variables which were World Health Organization functional class(WHO FC), 6-min walk distance (6MWD), N-terminal of the pro-hormone brain natriuretic peptide(NT-pro BNP), and right atrial area(RAA), then validated it in the prediction of one-year survival rate for patients with PAH by contrast with the REVEAL risk score.. For the validation cohort(n = 216), the predicted one-year survival rate were 95-100%, 90-95%, and < 90% in the mRASP risk score strata of 0-2, 3-5, and 6-8, respectively; meanwhile, the observed one-year survival rates were 97.1, 92.6, and 52.2%, in each corresponding stratum, respectively. The mRASP (c-index = 0.727) demonstrated similar predictive power in contrast with the REVEAL risk assessment score (c-index = 0.715) in the prediction of one-year survival rate.. The mRASP is an eligible risk assessment tool for the prognostic assessment of PAH. In contrast with the REVEAL score, it demonstrated similar predictive power and accuracy, with extra simplicity and convenience.

Topics: Adult; Aged; China; Cohort Studies; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Registries; Risk Assessment; Severity of Illness Index; Survival Rate

Topics: Body Mass Index; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Obesity; Registries

We aimed to investigate the prevalence of iron deficiency (ID) in congenital heart disease associated with pulmonary arterial hypertension (CHD-PAH) and to explore the influence of ID on CHD-PAH patients. What was associated with ID in these patients was also looked into.. One hundred and fifty-three patients who were newly diagnosed with CHD-PAH were enrolled. Patients were divided into iron-deficient and iron-replete groups according to the following criteria. ID was defined as transferrin saturation <20% in male and transferrin saturation <25% in female. Clinical data of all participants were collected and compared. Logistic regression was performed to explore factors associated with ID in CHD-PAH.. Thirty-nine percent of 153 CHD-PAH patients were founded with ID. Iron-deficient group had greater proportion of female patients, shorter six minutes walking distance (6-MWD), higher N-terminal pro-brain natriuretic peptide levels, lower creatinine levels, greater ratio of diastolic right ventricle diameter to left ventricle diameter. Female (OR = 15.44, 95%CI 4.91-48.54, p < .01), 6-MWD (OR = 0.99, 95%CI 0.98-1.00, p = .02) and mean right atrial pressure (OR = 1.13, 95%CI 1.02-1.26, p = .02) were independently associated with ID in the overall CHD-PAH patients. Menstruation was independently associated with ID in the female subgroup (OR = 3.88, 95%CI 1.09-13.84, p = .04).. ID was highly prevalent in CHD-PAH patients. Worse exercise tolerance and right heart function were observed in iron-deficient patients with CHD-PAH. Female, 6-MWD, mean right atrial pressure and menstruation are important variables indicating the presence of ID in CHD-PAH.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Atrial Function, Right; Atrial Pressure; Beijing; Biomarkers; Creatinine; Exercise Tolerance; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Male; Menstruation; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Retrospective Studies; Risk Factors; Sex Factors; Transferrin; Ventricular Function, Left; Ventricular Function, Right; Young Adult

Objective To investigate the influence of surgical correction on biomarkers of endothelial dysfunction in children with congenital heart disease and to evaluate anthropometric data. Methods Children with pulmonary hypertension (PH) or Tetralogy of Fallot (TOF) who were scheduled for corrective surgery were enrolled in this prospective study. Age-matched healthy children were included as controls. Demographic, haemodynamic and cardiac ultrasonography data were collected. Blood samples were taken pre-surgery, 24-48 hours post-surgery and again 3-6 months later. Several biomarkers (protein C, soluble platelet selectin [CD62P], soluble endothelium selectin [CD62E], soluble leukocyte selectin [CD62L], plasma von Willebrand Factor [vWF] atrial natriuretic peptide [ANP], brain natriuretic peptide[(BNP] and insulin-like growth factor-1 [IGF-1]) were measured. Results Sixty-three children (32 with PH, 15 with TOF, and 16 controls) were enrolled. No significant differences between the PH and TOF groups were observed in the expression of biomarkers pre- and post-surgery. IGF-1 levels were closely related to anthropometric data, particularly those children with PH. Expression of IGF-1 and weight/height normalized after corrective surgery. Conclusions No significant endothelial dysfunction was observed in children with PH or TOF before or after corrective surgery. Significant retardation of growth, particularly weight, was found before surgery and may be related to IGF-1 suppression.

Topics: Anthropometry; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; E-Selectin; Female; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Insulin-Like Growth Factor I; L-Selectin; Male; Natriuretic Peptide, Brain; P-Selectin; Prospective Studies; Protein C; Tetralogy of Fallot; Ultrasonography; von Willebrand Factor

Chronic inflammation emerges as a feature of the pathogenesis of pulmonary arterial hypertension (PAH) in experimental models. Alterations of circulating cell subsets have been observed in patients with PAH. We aimed to assess associations of the white blood cell count with disease severity and outcome in patients with PAH.. The total and differential white blood cell count was related to functional parameters, pulmonary hemodynamics and transplantation-free survival in 77 patients with PAH in an observational single center study.. An increased neutrophil/lymphocyte ratio was associated with poor World Health Organization functional class and shorter 6-minute walking distance, as well as with elevated right atrial pressure and high level of N-terminal prohormone of brain natriuretic peptide. During a median follow-up period of 31 months (range 16-56) 23 patients died and 2 patients were referred to lung transplantation. Using uni- and subsequent bivariate Cox proportional hazards analyses an increased neutrophil/lymphocyte ratio was associated with unfavorable transplantation-free survival independent of hemodynamic parameters and C-reactive protein. The prognostic implication sustained in subsets of patients with incident PAH and in the absence of cardiovascular risk factors.. The results of this analysis indicate that a neutrophilic inflammation may be associated with clinical deterioration and poor outcome in patients with PAH. Assessing the composition of the differential white blood cell count may render prognostic information and could represent a step towards incorporating an inflammatory marker into the clinical management of patients with PAH.

Topics: Aged; Biomarkers; C-Reactive Protein; Female; Germany; Hemodynamics; Humans; Hypertension, Pulmonary; Leukocyte Count; Lung Transplantation; Lymphocytes; Male; Middle Aged; Natriuretic Peptide, Brain; Neutrophils; Prognosis; Retrospective Studies; Risk Factors; Survival Analysis

Balloon pulmonary angioplasty (BPA) is a developing treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, to our knowledge there are no published data on BPA in CTEPH subjects aged 75 or over. The aim of the study was to analyze clinical and hemodynamic outcomes of sequential BPA in very elderly patients disqualified from pulmonary endarterectomy (PEA).. We enrolled 10 patients (4 male, 6 female, median age 81 [75-88]) with confirmed CTEPH, mPAP > 30 mmHg, and WHO class > II, disqualified from PEA. Overall, 10 patients underwent 39 BPA sessions (mean 3.9 sessions per patient, range 1-9), and 70 pulmonary arteries were dilated, (mean 6.5 vessels per patient, range 1-14).. Pulmonary angioplasty resulted in significant clinical and hemodynamic improvement in every patient: 6 MWT distance increased from a median of 221 m (80-320) to 345 (230-455) and plasma NT-proBNP levels decreased (P < 0.01). Sequential BPA resulted in normalization of mPAP (<25 mmHg) in 6 of 10 patients and mPAP decreased to 25-30 mmHg in three others. In the whole group mPAP decreased from 41 (31-53) mmHg to 23 (17-33) mmHg (P < 0.01). Overall, mean PAP and PVR decreased significantly in all cases, while CO and CI increased (P < 0.01). No severe complications occurred during BPA and over a median follow-up of 553 days (range 81-784), and all patients are still alive and in good general health.. This study demonstrated the safety and efficacy of refined BPA in CTEPH patients aged 75 or over, disqualified from PEA. Refined BPA may emerge as an alternative therapeutic strategy in very elderly CTEPH patients who are suitable for surgery, but this requires further validation in a large prospective study.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Chronic Disease; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Peptide Fragments; Poland; Prospective Studies; Pulmonary Artery; Pulmonary Embolism; Risk Adjustment; Treatment Outcome

The right ventricular longitudinal strain (RVLS) of pulmonary hypertension (PH) patients and its relationship with RV function parameters measured by echocardiography and hemodynamic parameters measured by right heart catheterization was investigated. According to the WHO functional class (FC), 66 PH patients were divided into FC I/II (group 1) and III/IV (group 2). RV function parameters were measured by echocardiographic examinations. Hemodynamic parameters were obtained by right heart catheterization. Patients in group 2 had higher systolic pulmonary artery pressure (sPAP; P < 0.05) than patients in group (1) significant between-group differences were observed in global RVLS (RVLS

Topics: Adult; Area Under Curve; Arterial Pressure; Biomarkers; Cardiac Catheterization; Echocardiography; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Image Interpretation, Computer-Assisted; Male; Middle Aged; Natriuretic Peptide, Brain; Observer Variation; Peptide Fragments; Predictive Value of Tests; Pulmonary Artery; Reproducibility of Results; Retrospective Studies; ROC Curve; Severity of Illness Index; Time Factors; Vascular Resistance; Ventricular Dysfunction, Right; Ventricular Function, Right; Walk Test

MicroRNA-206 (miR-206), a muscle-specific miRNA, regulates the growth of cardiac myocytes and pulmonary artery smooth muscle cells. However, it remains unknown whether miR-206 is involved in pulmonary hypertension (PH) due to left heart diseases (PH-LHD). This study was designed to investigate the correlation between miR-206 and PH in patients with LHD.. In 82 consecutively enrolled LHD patients, we examined the serum levels of miR-206 and analyzed its correlations with pulmonary artery systolic pressure (PASP) and cardiac function. Another 36 age- and sex-matched subjects served as healthy controls.. The patients were divided into the LHD group (n=47, PASP<50 mmHg) and the PH-LHD group (n=35, PASP≥50 mmHg). The level of miR-206 was significantly decreased in the PH-LHD group compared with that of the LHD and healthy control groups. In addition, the miR-206 level was correlated with PASP (r=-0.305, p<0.001) but not with systemic blood pressure. Univariate analyses showed that miR-206, brain natriuretic peptide (BNP), left ventricular ejection fraction and left atrial longitudinal diameter (LAD) were significantly related to PASP. Multivariate regression analysis identified miR-206 as an independent predictive factor for PH. MiR-206 alone (cut-off <0.66) demonstrated a sensitivity of 68.60% and a specificity of 65.80% in predicting PH. Moreover, the combination of miR-206, BNP and LAD (cut-off 0.21) showed a sensitivity of 97.10% and a specificity of 80.30% in predicting PH in LHD patients.. A decreased circulating miR-206 level was associated with increased PASP in LHD patients. Thus, the level of miR-206, especially combined with BNP and LAD, might be helpful in the detection of PH in LHD patients.

Topics: Adult; Aged; Area Under Curve; Blood Pressure; Echocardiography; Female; Heart Diseases; Hemodynamics; Humans; Hypertension, Pulmonary; Male; MicroRNAs; Middle Aged; Natriuretic Peptide, Brain; Regression Analysis; ROC Curve; Severity of Illness Index; Ventricular Function, Left

Pulmonary hypertension (PH) is characterized by abnormally increased pulmonary vascular pressure, leading to deteriorated right ventricular function and premature death. Pulmonary mean transit time (PMTT) and biventricular function response to exercise in first-pass radionuclide angiography (FP-RNA) may provide early detection and timely disease monitoring of PH. This study aimed to investigate the diagnostic and prognostic values of this imaging modality in PH patients.. Left and right ventricular ejection fraction (LVEF/RVEF) and PMTT at rest and immediately after exercise treadmill test were measured by FP-RNA in 77 consecutive patients with clinical presentations suggestive of PH (aged 46 ± 15 years, 33 men), mostly with symptoms of unexplained progressive dyspnea. These parameters, along with other clinical variables, were correlated with right-sided heart catheterization data and clinical outcomes.. Fifty patients (64.9%) were diagnosed as having definite PH. Besides higher N-terminal pro-B-type natriuretic peptide levels, right atrial pressure, and pulmonary vascular resistance, PH patients had significantly longer PMTT, lower LVEF after exercise and rest, and lower poststress RVEF (all P < 0.05), compared with non-PH subjects. Moreover, PH patients exhibited stress-induced right ventricular dysfunction and stationary poststress PMTT. Poststress PMTT and echocardiography had comparable diagnostic utility (area under the curve, 0.80 vs 0.84, respectively). Eighteen patients died during a median follow-up period of 380 days. Failure of exercise treadmill test, lower peak heart rate response, and stress/rest LVEF ratio of less than 90% using exercise treadmill FP-RNA were independent predictors of mortality in PH patients.. Exercise treadmill and rest FP-RNA provided diagnostic value and had prognostic implications in patients with PH.

Topics: Adult; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Rest; Stroke Volume; Ventricular Function, Left; Ventriculography, First-Pass

Persistent pulmonary hypertension of the newborn (PPHN) is a life‑threatening disease that is commonly observed in the neonatal intensive care unit. PPHN is pathologically characterized by pulmonary vascular remodeling and, in particular, pulmonary artery smooth muscle cell (PASMC) proliferation. Decreased expression levels of peroxisome proliferator‑activated receptor γ (PPAR‑γ), which is a member of the nuclear receptor hormone superfamily, in combination with elevated expressions of transient receptor potential cation channel, subfamily C, member 1 (TRPC1) and TRPC6 contributes to the PASMC proliferation and excessive pulmonary vascular remodeling in adult pulmonary hypertension (PH). Whether PPAR‑γ, TRPC1 and TRPC6 affect the development of vascular remodeling in PPHN model rats remains unknown. The aim of the present study was to investigate the roles of PPAR‑γ, TRPC1 and TRP6 on the pathogenesis of PPHN in rats. The rat model of PPHN was established by exposure to hypoxic conditions and indomethacin treatment. Lung tissues, hearts and blood from PPHN model and Control rats were collected and examined. Parameters, including the percentage of medial wall thickness (WT %), the percentage of medial wall area (WA %), right ventricular hypertrophy (RVH) and the plasma concentration of B‑type natriuretic peptide (BNP) were used to estimate the development of PPHN. The expression levels of PPAR‑γ, TRPC1 and TRPC6 in lung tissues were detected by immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction. Significant increases were observed in the WT %, WA %, RVH and plasma BNP in the PPHN group compare with the Control group (P<0.01). In addition, the mRNA and protein expression levels of PPAR‑γ were markedly downregulated (P<0.05 vs. Control). In the PPHN group, the protein expression levels of TRPC1 and TRPC6 were higher compared to the control group; however, there was no difference in the mRNA expression levels (P>0.05). In conclusion, the present study successfully established a PPHN rat model, and the altered expressions of PPAR‑γ, TRPC1 and TRPC6 in the pulmonary artery located in the lungs of newborn rats with PPHN suggested that these proteins may be important mediators of PPHN.

Topics: Animals; Animals, Newborn; Disease Models, Animal; Female; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lung; Natriuretic Peptide, Brain; PPAR gamma; Protein Transport; Rats; Rats, Sprague-Dawley; RNA, Messenger; TRPC Cation Channels; Vascular Remodeling

Increased right atrial size is related to adverse prognosis in pulmonary hypertension. The potential incremental value of right atrial function assessment is still unclear. We tested the relationship between right atrial two-dimensional speckle-tracking echocardiography impairment and hemodynamic, functional and clinical deterioration in patients with pulmonary hypertension.. We prospectively evaluated 36 patients (27 female, 9 male; mean age 68 ± 13 years) with suspected pulmonary hypertension undergoing right heart catheterization and 16 matched controls. All patients underwent baseline evaluation by New York Heart Association functional class, 6-min walking test, brain natriuretic peptide (BNP), and standard two-dimensional echocardiography in less than 48 h of right heart catheterization. Right atrial two-dimensional speckle-tracking echocardiography was assessed by averaging all segments in standard four-chamber apical view.. Right atrial global integral strain was significantly lower in patients compared with controls (11.40 ± 5.22% vs. 25.72 ± 5.95 P < 0.001). Moreover, right atrial global strain, but not right atrial area or volume, was correlated with invasively measured cardiac index (CI) (r = 0.72; P < 0.0001) and pulmonary vascular resistances in all patients, even though stronger in subjects with precapillary pulmonary hypertension (r = -0.42, P = 0.018; r = -0.54, P = 0.007 respectively; P = 0.007). It was also correlated with New York Heart Association (P = 0.027), BNP (P = 0.002), and 6-min walking test (P = 0.006). After multivariate analysis including right atrial volume, tricuspid annular plane systolic excursion, left atrial strain, and BNP, right atrial global strain showed the strongest correlation with CI. Area under the curve optimal cutoff for predicting CI at least 2.4 l/min/m was 17% (area under the curve: 0.83, sensitivity: 90%, specificity: 54%).. Right atrial global strain can identify right atrial functional impairment before structural changes and may be implemented in a comprehensive, noninvasive right heart assessment for diagnosis and follow-up of pulmonary hypertension patients.

Topics: Adult; Aged; Aged, 80 and over; Cardiac Catheterization; Early Diagnosis; Echocardiography, Doppler; Female; Heart Atria; Hemodynamics; Humans; Hypertension, Pulmonary; Italy; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Sensitivity and Specificity; Walk Test

Adipose tissues secrete adipokines, peptides with potent effects modulating fibrosis, inflammation, and vascular homeostasis. Dysregulated adipose tissue biology and adipokine balance have recently been implicated in systemic sclerosis (SSc). This study was undertaken to determine whether altered circulating adipokine levels correlate with SSc disease subsets or clinical manifestations.. Multiplex assays were used to measure circulating adipokine levels in 198 patients with SSc and 33 healthy controls. Data were evaluated for correlations between serum adipokine levels and demographic and clinical features, including pulmonary arterial hypertension (PAH). To assess the relevance of adipsin, an adipokine involved in complement pathway activation, in SSc, we analyzed publicly available genetic and transcriptomic data.. Levels of adiponectin and adipsin differed significantly between controls and patients. Adipsin was significantly elevated in patients with limited cutaneous SSc (odds ratio [OR] 28.3 [95% confidence interval (95% CI) 7.0-113.8]; P < 0.0001), and its levels were associated with serum autoantibody status, pulmonary function and cardiovascular parameters, and PAH (OR 3.3 [95% CI 1.3-8.7]; P = 0.02). Elevated adipsin was more strongly associated with PAH than B-type natriuretic peptide was. Moreover, in SSc patients, adipsin gene single-nucleotide polymorphisms were associated with PAH. Transcriptome data set analysis demonstrated elevated adipsin expression in patients with SSc-related PAH.. We identify adipsin as a novel adipose tissue-derived marker of SSc-related PAH. Circulating adipsin levels might serve as predictive biomarkers in SSc. Mechanistically, adipsin might represent a pathogenic link between adipocyte dysfunction and complement pathway activation and play an important role in the pathogenesis of SSc-related PAH.

Topics: Adiponectin; Adult; Aged; Autoantibodies; Complement Factor D; Cytokines; Female; Gene Expression Profiling; Humans; Hypertension, Pulmonary; Leptin; Male; Middle Aged; Natriuretic Peptide, Brain; Nicotinamide Phosphoribosyltransferase; Odds Ratio; Polymorphism, Single Nucleotide; Resistin; Scleroderma, Diffuse; Scleroderma, Limited

In pulmonary arterial hypertension (PAH), upfront combination therapy is associated with better clinical outcomes and a greater reduction in N-terminal pro-brain natriuretic peptide (NT-proBNP) than monotherapy. NT-proBNP levels reflect right ventricular (RV) wall stress, which increases when the right ventricle dilates. This study explored the impact of upfront combination therapy on RV volumes compared with monotherapy in PAH patients.This retrospective study involved 80 incident PAH patients (New York Heart Association class II and III) who were treated with upfront combination therapy (n=35) (

Topics: Adult; Aged; Cardiac Catheterization; Drug Therapy, Combination; Endothelin Receptor Antagonists; Female; Heart Ventricles; Humans; Hypertension, Pulmonary; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Retrospective Studies; Stroke Volume; Vascular Resistance; Ventricular Function, Right

Riociguat, the first approved drug for patients with chronic thromboembolic pulmonary hypertension (CTEPH), is a soluble guanylate cyclase (sGC) Stimulator. It directly stimulates sGC independently of nitric oxide (NO) and increases sGC sensitivity for NO. The safety and efficacy of transitioning from a phosphodiesterase 5 inhibitor (PDE5i) to riociguat is unknown.. Twenty-three patients were prospectively enrolled: 8 symptomatic patients with inadequate clinical responses to PDE5i were changed to riociguat (transitioned group); 15 started riociguat anew (new or add-on group). We analyzed the change from baseline to 6-12 months of riociguat treatment for the 6-minute walk distance (6MWD), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index (CI), partial pressure of oxygen in arterial blood (PaO2), brain natriuretic peptide (BNP), World Health Organization (WHO) functional class, safety and adverse events. The mPAP, BNP and WHO functional class significantly improved in total. In the transitioned group, BNP significantly decreased by -116.5±188.6pg/ml (P=0.0156). The 6MWD, mPAP, PVR, CI, and PaO2 improved but not significantly. The baseline condition was significantly more severe in the transitioned than in the new or add-on group. No patients discontinued riociguat. Relatively rapid transitioning from PDE5i to riociguat was safe under careful observation.. Transitioning to riociguat may be safe and effective in CTEPH patients with inadequate clinical responses to PDE5i.

Topics: Aged; Arterial Pressure; Chronic Disease; Drug Substitution; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Partial Pressure; Phosphodiesterase 5 Inhibitors; Pulmonary Artery; Pulmonary Embolism; Pyrazoles; Pyrimidines; Time Factors; Vascular Resistance; Walk Test

The 2015 European pulmonary hypertension (PH) guidelines propose a risk stratification strategy for patients with pulmonary arterial hypertension (PAH). Low-, intermediate- and high-risk strata are defined by estimated 1-year mortality risks of <5%, 5-10% and >10%, respectively. This risk assessment strategy awaits validation.We analysed data from patients with newly diagnosed PAH enrolled into COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension), a European-based PH registry. An abbreviated version of the risk assessment strategy proposed by the European PH guidelines was applied, using the following variables: World Health Organization functional class, 6-min walking distance, brain natriuretic peptide or its N-terminal fragment, right atrial pressure, cardiac index and mixed venous oxygen saturation.Data from 1588 patients were analysed. Mortality rates were significantly different between the three risk strata (p<0.001 for all comparisons). In the entire patient population, the observed mortality rates 1 year after diagnosis were 2.8% in the low-risk cohort (n=196), 9.9% in the intermediate-risk cohort (n=1116) and 21.2% in the high-risk cohort (n=276). In addition, the risk assessment strategy proved valid at follow-up and in major PAH subgroups.An abbreviated version of the risk assessment strategy proposed by the current European PH guidelines provides accurate mortality estimates in patients with PAH.

Topics: Adult; Aged; Aged, 80 and over; Europe; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Prospective Studies; Registries; Risk Assessment; Severity of Illness Index; Walk Test

Topics: Adult; Aged; Atrial Pressure; Biomarkers; Female; France; Humans; Hypertension, Pulmonary; Lung Transplantation; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Practice Guidelines as Topic; Prognosis; Registries; Retrospective Studies; Risk Assessment; Survival Analysis; Walk Test; World Health Organization

We aimed to investigate plasma growth differentiation factor-15 (GDF-15) levels in pediatric pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD), and assess the association with hemodynamic parameters. Plasma GDF-15 levels were measured in children with PAH-CHD (n = 46) and compared to children with CHD without PAH (n = 39). Normal individuals (n = 30) served as health control group. Plasma GDF-15 levels were significantly elevated in patients with PAH-CHD compared with those with CHD without PAH (median 1415 ng/L, interquartile range [IQR] 926.7-2111.7 ng/L vs. 890.6 ng/L, IQR 394.7-1094.3 ng/L, p < 0.01). Elevated plasma GDF-15 levels were positively related to Functional Class, uric acid, N-terminal pro-B-type natriuretic peptide (NT-proBNP), pulmonary artery systolic pressure, mean pulmonary artery pressure, pulmonary blood flow/systemic blood flow and pulmonary vascular resistance, and a lower mixed venous oxygen saturation (Sv

Topics: Area Under Curve; Biomarkers; Cardiac Catheterization; Child; Child, Preschool; Female; Growth Differentiation Factor 15; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Infant; Male; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity

A proportion of pulmonary arterial hypertension (PAH) patients do not reach treatment goals with phosphodiesterase-5 inhibitors (PDE5i). RESPITE investigated the safety, feasibility and benefit of switching from PDE5i to riociguat in these patients.RESPITE was a 24-week, open-label, multicentre, uncontrolled study. Patients in World Health Organization (WHO) functional class (FC) III, with 6-min walking distance (6MWD) 165-440 m, cardiac index <3.0 L·min

Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Endothelin Receptor Antagonists; Europe; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; North America; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Prospective Studies; Pyrazoles; Pyrimidines; Severity of Illness Index; Treatment Outcome; Vascular Resistance; Walk Test; World Health Organization; Young Adult

Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are categorized as Group 1' in the clinical classification of pulmonary hypertension. No medical therapy has been proven to be effective in patients with PVOD/PCH. Imatinib is a molecular targeted drug and was expected to be effective in patients with pulmonary arterial hypertension. We evaluated its efficacy and safety in patients with PVOD/PCH.. In the present observational study, 9 patients with PVOD/PCH received imatinib. Clinical data including exercise capacity and hemodynamics at baseline and at follow-up were compared. Survival rate of patients treated with imatinib was compared to those of 7 patients who did not treated with imatinib.. Imatinib was prescribed at doses of 100-400 mg/day and was well-tolerated. At follow-up, World Health Organization functional class and brain natriuretic peptide levels significantly improved. Mean pulmonary arterial pressure was significantly reduced (from 56.8 ± 8.3 to 43.7 ± 9.0 mmHg) with preserved cardiac index. Patients were treated with imatinib for 797.2 ± 487.0 days. Seven patients (77.8%) died and 2 patients (22.2%) underwent lung transplantation. Mean survival time in patients treated with imatinib therapy was 1493.7 ± 196.3 days (95% confidence interval, 1108.9-1878.5 days), significantly longer than those without imatinib treatment (713.0 ± 258.1 days, log-rank test, P = 0.04).. Imatinib improved exercise capacity, hemodynamics and survival in patients with PVOD/PCH. In patients with PVOD/PCH, who have no effective medical therapy available, imatinib might function as a bridge to lung transplantation, and may become a potential therapeutic option to improve their survival.

Topics: Adult; Exercise Tolerance; Hemangioma, Capillary; Hemodynamics; Humans; Hypertension, Pulmonary; Imatinib Mesylate; Kaplan-Meier Estimate; Lung Neoplasms; Lung Transplantation; Male; Middle Aged; Natriuretic Peptide, Brain; Protein Kinase Inhibitors; Pulmonary Veno-Occlusive Disease; Severity of Illness Index; Survival Rate; Treatment Outcome; Walk Test; Young Adult

To observe the clinical parameters and short-term prognosis of Tibetan high-altitude area children with congenital heart disease undergoing surgery and anaesthesia in low-altitude area, and to investigate the perioperative safety of the treatment.
 Methods: From January, 2016 to December, 2016, 14 children with congenital heart disease who underwent surgery were assigned into 2 groups (n=7 each): the high-altitude area group (X group, children from Tibetan Autonomous Region) and the low-altitude area group (H group, children from Hunan Province). Echocardiography data, perioperative hemodynamic changes, postoperative recovery, complication and perioperative serum N terminal pro B type natriuretic peptide (NT-proBNP) levels were recorded.
 Results: There were no significant differences in cardiac structure and function between the 2 groups, while the incidence of pulmonary hypertension in the X group was significantly higher than that in the H group (P<0.05). There were no significant differences in perioperative hemodynamics between the 2 groups (P>0.05), while the duration in ICU in the X group was longer than that in the H group and the serum NT-proBNP level in the X group was higher than that in the H group (P<0.05).
 Conclusion: For children with congenital heart disease in Tibetan high-altitude area, undergoing surgery in low-altitude area contributes to a steady perioperative hemodynamics and helps to increase the perioperative safety. There may be a higher risk of postoperative cardiac dysfunction in Tibetan children than that in low-altitude area.. 目的：观察高海拔地区先天性心脏病患儿到低海拔地区行先天性心脏病矫治手术的临床指标和短期预后，以探讨其围手术期的安全性。方法：回顾性分析2016年1至12月在中南大学湘雅医院择期行先天性心脏病矫治手术的来自西藏自治区(X组)和湖南省(H组)的患儿各7例。比较两组患儿心脏超声心动图检查指标、围手术期血流动力学、术后恢复与并发症和围手术期氨基末端脑钠肽前体(N terminal pro B type natriuretic peptide，NT-proBNP)水平。结果：心脏超声心动图显示两组患儿心脏结构和心功能无明显差异，X组患儿肺高压的发生率明显高于H组(P<0.05)。围手术期血流动力学比较两组之间差异无统计学意义(P>0.05)，术后ICU停留时间X组患儿更长(P<0.05)。血清NT-proBNP水平X组患儿明显高于H组(P<0.05)。结论：高海拔地区的先天性心脏病患儿到低海拔地区行先天性心脏病矫治手术有助于提高围手术期安全性，麻醉手术中血流动力学平稳，但术后心功能不全风险仍高于低海拔地区患儿，术后恢复时间延长。.

Topics: Altitude; Anesthesia; Biomarkers; Cardiac Surgical Procedures; Child; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Patient Safety; Peptide Fragments; Perioperative Period; Postoperative Complications; Prognosis; Tibet

Subcutaneous treprostinil is a prostacyclin analogue used to treat pulmonary arterial hypertension (PAH). Due to local pain it can cause a deterioration of heart related quality of life (HRQoL) or even abandonment of treatment. The aim of this paper was to assess the feasibility of treatment with intravenous treprostinil administered by means of the Lenus Pro® implantable pump.. This was a retrospective, multi-center study involving 12 patients (8 females) with PAH treated with a subcutaneous infusion of treprostinil with intolerable pain at the infusion site. Clinical evaluation, including HRQoL assessment with SF-36 questionnaire was performed, before pump implantation and 2-9 months after. The median time of follow-up time was 14 months (4-29 months).. After implantation of the Lenus Pro® pump, no statistically significant changes were observed in the 6-min walking distance and NT-proBNP. After implantation 50% of patients were in II WHO functional class (33% before, p = 0,59). There was a significant improvement in HRQoL within the Physical Component Score (28 ± 7 vs 38 ± 8 pts., p < 0,001) and in specific domains of SF-36 form: physical role (31 ± 7 pts. vs. 41 ± 12 pts., p = 0,03), bodily pain (31 ± 12 vs. 50 ± 14 pts., p = 0,02), and vitality (37 ± 8 pts. vs. 50 ± 14 pts., p = 0,03). During the periprocedural period, one patient developed a recurrent haematoma at the implantation site. During follow-up in one patient, the drug delivering cannula slipped out of the subclavian vein, what required repositioning repeated twice, and in another patient an unexpected increase in the drug administration rate was observed.. In patients with PAH who do not tolerate subcutaneous infusion of treprostinil, the use of the Lenus Pro® implantable pump results in significant subjective improvement of vitality and physical aspect of the HRQoL with acceptable safety profile.

Topics: Administration, Intravenous; Adult; Aged; Antihypertensive Agents; Catheters, Indwelling; Epoprostenol; Equipment Failure; Female; Hematoma; Humans; Hypertension, Pulmonary; Infusion Pumps, Implantable; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Retrospective Studies; Walk Test

N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is currently used as a surrogate marker for disease severity in pulmonary hypertension (PH). However, NT-proBNP tends to have a high variability and may insufficiently correlate with hemodynamics and exercise capacity.. To investigate the association of NT-proBNP with hemodynamics and cardio-pulmonary exercise testing (CPET) in 84 therapy-naive patients with precapillary PH.. NT-proBNP levels were significantly correlated with hemodynamics and CPET parameters except for cardiac index, diffusion capacity, PaO. NT-proBNP is associated with disease severity in precapillary PH. The association might be age- and gender-dependent. NT-proBNP may insufficiently correlate with disease severity in CTEPH, possibly due to comorbidity.

Topics: Age Factors; Aged; Exercise Tolerance; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Sex Factors; Walk Test

Elevated right atrial (RA) pressure is a risk factor for mortality, and RA size is prognostic of adverse outcomes in pulmonary hypertension (PH). There is limited data on phasic RA function (reservoir, conduit, and pump) in pediatric PH. We sought to evaluate (1) the RA function in pediatric PH patients compared with controls, (2) compare the RA deformation indices with Doppler indices of diastolic dysfunction, functional capacity, biomarkers, invasive hemodynamics, and right ventricular functional indices, and (3) evaluate the potential of RA deformation indices to predict clinical outcomes.. Sixty-six PH patients (mean age 7.9±4.7 years) were compared with 36 controls (7.7±4.4 years). RA and right ventricular deformation indices were obtained using 2-dimensional speckle tracking (2DCPA; TomTec, Germany). RA strain, strain rates, emptying fraction, and right ventricular longitudinal strain were measured. RA function was impaired in PH patients versus controls (. RA deformation properties are significantly altered in pediatric PH patients. Progressive worsening of RA reservoir and conduit functions is related to changes in right ventricular diastolic dysfunction. RA reservoir function, pump function, the rate of atrial filling, and atrial minimum volume emerged as outcome predictors in pediatric PH.

Topics: Biomarkers; Case-Control Studies; Child; Colorado; Diastole; Disease Progression; Echocardiography, Doppler; Exercise Test; Female; Heart Atria; Hemodynamics; Humans; Hypertension, Pulmonary; Image Interpretation, Computer-Assisted; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Retrospective Studies; Systole; Vascular Resistance; Ventricular Dysfunction, Right

Akın A, Alehan D, Aykan HH, Özkutlu S, Özer S, Karagöz T. Evaluation of Tissue Doppler Echocardiographic Imaging findings in children with pulmonary hypertension. Turk J Pediatr 2017; 59: 244-253. Tissue Doppler Imaging has become an important prognostic marker that can be used in follow-up and determination of the prognosis in pulmonary hypertension patients. We compared the Tissue Doppler imaging parameters of 34 patients with pulmonary hypertension and 43 healthy controls. In addition, Brain-Natriuretic Peptide levels, pulmonary artery systolic pressures measured with echocardiography, 6-minute walking tests and New York Heart Association functional classification were compared. Among patients with Eisenmenger syndrome and idiopathic pulmonary hypertension, Tissue Doppler imaging parameters were mostly similar. In patients with New York Heart Association functional class 3, mitral septal annulus E/Ea (p=0.050) and mitral lateral annulus myocardial performance index (p=0.009) were higher than class 2 patients. In patients with higher Brain Natriuretic Peptide level, mitral lateral annulus and tricuspid septal annulus Ea/Aa values were lower (p=0.046 and < 0.001 respectively); tricuspid septal annulus E/Ea and interventricular septum myocardial performance index values were higher than in patients with normal Brain-Natriuretic Peptide level (p=0.006). In conclusion tissue Doppler imaging findings were significantly impaired in children with pulmonary hypertension compared to the control group. Findings were similar in patients with idiopathic pulmonary hypertension and Eisenmenger syndrome. Mitral lateral annulus myocardial performance index value may have a prognostic importance due its significant association with poor functional class. Due to the significant associations between mitral lateral annulus, tricuspid septal annulus Ea/Aa, tricuspid septal annulus Ea and E/Aa, interventricular septum-myocardial performance index values and brain natriuretic peptide levels, these parameters may be used in evaluating response to therapy.

Topics: Adolescent; Adult; Child; Child, Preschool; Echocardiography, Doppler; Female; Heart; Humans; Hypertension, Pulmonary; Infant; Male; Natriuretic Peptide, Brain; Prognosis; Pulmonary Artery; Walk Test; Young Adult

The aim of this study was to evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH) and changes after therapy with bosentan.. Twenty-one patients with SSc-PAH on bosentan therapy were enrolled. PAH was diagnosed by right heart catheterization. NT-proBNP levels, 6-min walking test (6MWT), Doppler echocardiography to estimated systolic pulmonary arterial pressure (sPAP), New York Heart Association (NYHA) functional class for dyspnea and carbon monoxide lung diffusion capacity (DLco) were recorded at baseline, and after 1 and 2 years. Fifty-two SSc patients without PAH were also evaluated as controls.. NT-proBNP plasma levels were significantly higher in SSc-PAH at 385 pg/mL (SD ± 427) than in SSc without PAH and 72 pg/mL (SD ± 52, P < 0.001) at baseline, but did not significantly change following bosentan therapy at 1 year (330 pg/mL [SD ± 291] and 2 years (374 pg/mL [SD ± 291]). However, NYHA class significantly improved at 2 years (P = 0.01) as well as 6MWT (P = 0.04). NT-proBNP levels were positively correlated only with sPAP but not with DLco, NYHA class or 6MWT.. NT-proBNP levels were found to be significantly higher in SSc-PAH at baseline. Serial assessment of NT-proBNP in SSc-PAH patients on bosentan therapy showed no relation to the clinical improvement. This suggests that NT-proBNP may lack 'sensitivity to change', but further studies are warranted to assess the role of NT-proBNP as a biomarker of the therapeutic response in larger cohorts of SSc patients.

Topics: Adult; Aged; Antihypertensive Agents; Biomarkers; Blood Pressure; Bosentan; Endothelin Receptor Antagonists; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Recovery of Function; Scleroderma, Systemic; Sulfonamides; Time Factors; Treatment Outcome; Up-Regulation

Pulmonary arterial hypertension (PAH) is one of the most devastating complications in scleroderma (SSc) patients and has a poorer outcome than other PAH subgroups. Tadalafil (Adcirca. We enrolled 10 SSc-PAH subjects who were naïve to PDE5-I treatment, profiled gene expression in whole blood prior to and following treatment with tadalafil, measured changes in genomic profiles before and after treatment with tadalafil, and correlated them with changes in clinical outcomes, such as cardiopulmonary hemodynamics, six-min walk distance (6MWD), Borg Dyspnea Index (BDI), NYHA/WHO functional class (FC), B-type natriuretic peptide (BNP), and cardiac magnetic resonance imaging (cMRI).. Genes associated with IL-12 signaling and extracellular matrix maintenance were coordinately up- or down-regulated with treatment, respectively, across all subjects. Interestingly, we found that genes encoding voltage-gated potassium channels and genes related to innate immunity were coordinately up-regulated in subjects who improved with tadalafil treatment compared to those patients who did not. In contrast, up-regulation of Golgi-related gene sets was associated with clinical worsening during the treatment period.. The results of this pilot study suggest that outcomes of SSc-PAH patients treated with tadalafil are associated with specific changes in gene expression and biological pathways.

Topics: Aged; Down-Regulation; Extracellular Matrix; Female; Golgi Apparatus; Humans; Hypertension, Pulmonary; Immunity, Innate; Interleukin-12; Male; Microarray Analysis; Middle Aged; Natriuretic Peptide, Brain; Phosphodiesterase 5 Inhibitors; Pilot Projects; Potassium Channels, Voltage-Gated; Scleroderma, Systemic; Signal Transduction; Tadalafil; Transcriptome; Treatment Outcome; Up-Regulation; Walk Test

Pulmonary hypertension (PH) is an important cause of morbidity and mortality in patients with SSc. The submaximal heart and pulmonary evaluation (step test) is a non-invasive, submaximal stress test that could be used to identify SSc patients with PH. Our aims were to determine whether change in end tidal carbon dioxide ([Formula: see text]) from rest to end-exercise, and the minute ventilation to carbon dioxide production ratio ([Formula: see text]), both as measured by the step test, differ between SSc patients with and without PH. We also examined differences in validated self-report questionnaires and potential PH biomarkers between SSc patients with and without PH.. We performed a cross-sectional study of 27 patients with limited or dcSSc who underwent a right heart catheterization within 24 months prior to study entry. The study visit consisted of questionnaire completion; history; physical examination; step test performance; and phlebotomy. [Formula: see text], [Formula: see text], self-report data and biomarkers were compared between patients with and without PH.. SSc patients with PH had a statistically significantly lower median (interquartile range) [Formula: see text] than SSc patients without PH [-2.1 (-5.1 to 0.7) vs 1.2 (-0.7 to 5.4) mmHg, P = 0.035], and a statistically significantly higher median (interquartile range) [Formula: see text] [53.4 (39-64.1) vs 36.4 (31.9-41.1), P = 0.035]. There were no statistically significant differences in self-report data or biomarkers between groups.. [Formula: see text] and [Formula: see text] as measured by the step test are statistically significantly different between SSc patients with and without PH. [Formula: see text] and [Formula: see text] may be useful screening tools for PH in the SSc population.

Topics: Aged; Breath Tests; Carbon Dioxide; Cross-Sectional Studies; Exercise Test; Female; Humans; Hypertension, Pulmonary; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-6; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Gas Exchange; Pulmonary Ventilation; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Scleroderma, Diffuse; Scleroderma, Limited; Scleroderma, Systemic; Vascular Endothelial Growth Factor A

No unified method exists to effectively predict and monitor progression of pulmonary arterial hypertension (PAH). We assessed the longitudinal relationship between a novel marker of cardiopulmonary reserve and established prognostic surrogate markers in patients with pulmonary vascular disease.. Twenty participants with confirmed (n = 14) or at high risk (n = 6) for PAH underwent cardiovascular magnetic resonance (CMR) at baseline and after ~6 months of guideline-appropriate management. Ten PAH participants underwent RHC within 48 h of each CMR. RHC (mean pulmonary arterial pressure, mPAP; pulmonary vascular resistance index, PVRI; cardiac index, CI) and phase-contrast CMR (mean pulmonary arterial blood flow velocity, meanPAvel) measurements were taken at rest and during continuous adenosine infusion (70/140/210 mcg/kg/min). Initial meanPAvel's (rest and hyperemic) were correlated with validated surrogate prognostic parameters (CMR: RV ejection fraction, RVEF; RV end systolic volume indexed, RVESVI; RHC: PVRI, CI; biomarker: NT-pro brain natriuretic peptide, NTpBNP; clinical: 6-min walk distance, 6MWD), a measure of pulmonary arterial stiffness (elastic modulus) and volumetric estimation of RV ventriculoarterial (VA) coupling. Changes in meanPAvel's were correlated with changes in comparator parameters over time. At initial assessment, meanPAvel at rest correlated significantly with PVRI (inversely), CI (positively) and elastic modulus (inversely) (R. MeanPAvel during peak hyperemia correlated with invasive, non-invasive and clinical prognostic parameters at different time points. Further studies with predefined clinical endpoints are required to evaluated if this novel tool is a marker of disease progression in patients with pulmonary vascular disease.

Topics: Adenosine; Adult; Aged; Arterial Pressure; Biomarkers; Cardiorespiratory Fitness; Disease Progression; Elastic Modulus; Female; Hemodynamics; Humans; Hyperemia; Hypertension, Pulmonary; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Predictive Value of Tests; Prognosis; Prospective Studies; Pulmonary Artery; Stroke Volume; Time Factors; Vascular Resistance; Vascular Stiffness; Vasodilator Agents; Ventricular Function, Right; Walk Test

Topics: Blood Gas Analysis; Carbon Dioxide; Cardiac Catheterization; China; Chronic Disease; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Respiratory Function Tests; Severity of Illness Index; Thromboembolism

Topics: Adult; Catheterization; Diagnosis, Differential; Dyspnea; Echocardiography; Hemoptysis; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Pulmonary Embolism; Thrombolytic Therapy; Tomography, X-Ray Computed

Surviving pulmonary embolism (PE) brings a risk of thromboembolic disease chronicity. Chronic thromboembolic pulmonary hypertension (CTEPH) develops as a result of one or multiple pulmonary embolic events. It is an incapacitating long-term complication of thromboembolic disease with a negative impact on the patient's quality of life and prognosis. Contemporary pharmacological and especially surgical treatment possibilities offer hope for the patient's full recovery, but an early diagnosis is crucial for success.. In a prospective study cohort of 97 consecutive patients with a proven diagnosis of PE as the first documented thromboembolic event we tried to estimate the incidence of CTEPH during a 2-year follow-up.. Four individuals from our study population developed CTEPH, which represents an incidence of 4.2%.. Chronic thromboembolic pulmonary hypertension in pulmonary embolism survivors is a not uncommon complication deserving the attention of clinicians. Patients at risk of CTEPH can be identified for effective follow-up according to echocardiographic finding of elevated pulmonary artery systolic pressure and NT-proBNP levels at the time of hospital discharge.

Topics: Chronic Disease; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Pulmonary Embolism; Recurrence; Risk Factors; Thromboembolism

Pulmonary arterial hypertension (PAH) is a rare progressive disease of the pulmonary arterioles with an unfavourable prognosis.. To evaluate survival and prognostic factors in patients with PAH diagnosed and treated at a single centre in the years 2004–2013.. The study included 55 children (33 girls; 66%, 22 boys; 33%), with an average age 6.2 ± 6.0 years, with idiopathic PAH — n = 23 (42%), PAH associated with systemic-to-pulmonary shunts — n = 17 (31%), and PAH after corrective cardiac surgery — n = 15 (27%). Forty-seven of them (87%) were treated with advanced therapy.. During the follow-up with an average time of 5.6 ± 4.7 years 15 (27.3%) children died. The one-, three-, five-, and ten-year survival was, respectively, 83.1%, 77.1%, 70.7%, and 65.2%. The analysis of the survival curves revealed a better prognosis in patients with baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) level < 605 pg/mL (p = 0.024) and a higher probability of survival of three and five years in children at baseline I/II World Health Organisation functional class (WHO-FC). The higher risk of death was associated with a higher pressure in the right atrium (HR 1.23, p < 0.01) and higher pulmonary resistance (HR 1.1, p < 0.01), whereas no history of syncope had a better prognosis (HR 0.31, p = 0.03).. Survival in the study group was comparable to the currently published register data. Mortality risk factors were connected with the severity of the disease at diagnosis.

Topics: Adolescent; Child; Child, Preschool; Female; Humans; Hypertension, Pulmonary; Infant; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Factors

The evidence about prevalence, associated factors of pulmonary hypertension (PH) and its impact on patient's outcomes is limited.. We included 211 haemodialysis patients, we estimated the systolic pulmonary artery pressure (SPAP) by 2D Doppler echocardiography defining PH as a SPAP above 35 mmHg, the median follow-up was 39 (19-56) moths, and the primary endpoints were all cause mortality and cardiovascular events.. We found PH in 91 patients (43.9%). Independent determinants of PH were age, previous cardiovascular disease, the Nt-pro-BNP level hs-TnT, the systolic dysfunction, diastolic dysfunction and left ventricular hypertrophy. Over the follow-up 94 cardiovascular events occurred, variables associated were: PH, age, history cardiovascular disease, dyslipidaemia, elevated concentration of Nt-pro-BNP and hs-TnT, systolic and diastolic dysfunction, in a multivariate model, the PH maintained its independent association. Mortality data: 88 patients died (41.7%); 35 (29.5%) in the no PH group and 53 (58.5%) in the PH group (P < 0.001). In the Cox survival analysis, we found an association between mortality and age, previous cardiovascular disease, history of peripheral vascular disease, Nt-pro-BNP levels. In a multivariate model the PH remains as independent predictor of mortality.. Pulmonary hypertension is a common finding in HD patients and a valuable predictor of mortality and cardiovascular events. Prospective studies are needed to assess the effect of intervention on risk factors in improving patient's outcomes.

Topics: Age Factors; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Chi-Square Distribution; Echocardiography, Doppler; Female; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Kidney Diseases; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prevalence; Prognosis; Proportional Hazards Models; Renal Dialysis; Risk Factors; Spain; Time Factors

Recent data indicate that right ventricular systolic dysfunction (RVSD) by cardiac magnetic resonance imaging (CMR) is a strong predictor of outcome in heart failure. However, the prognostic significance of RVSD by CMR in heart failure with preserved ejection fraction (HFpEF) is unknown.. We prospectively enrolled 171 HFpEF patients who underwent CMR in addition to invasive and non-invasive testing. RVSD, defined as right ventricular (RV) EF <45% by CMR, was present in 33 (19.3 %) patients. Patients were followed for 573 ± 387 days, during which 41 had a cardiac event. Patients with RVSD presented with more frequent history of AF (P = 0.038), significantly higher resting heart rate (P = 0.009), shorter 6-min walk distance (P = 0.036), and higher NT-pro BNP serum levels (P < 0.001), and were more symptomatic (P < 0.001). With respect to haemodynamic parameters, RVSD was associated with respect to haemodynamic parameters, RVSD was associated with higher diastolic pulmonary artery pressure (P = 0.045), with higher pulmonary vascular resistance (P = 0.048), higher transpulmonary gradient (P = 0.042), and higher diastolic pulmonary vascular pressure gradient (P = 0.007). In the multivariable Cox analysis, RVSD (P < 0.001) remained significantly associated with cardiac events, in addition to diabetes (P = 0.011), 6-min walk distance (P = 0.018), and systolic pulmonary artery pressure (P = 0.003).. Although HFpEF is considered a disease of the left ventricle, respective imaging parameters are not related to outcome. In contrast, RVSD by CMR is independently associated with mortality and clinical status in these patients, and provides a useful tool for risk stratification.

Topics: Aged; Austria; Cardiac Catheterization; Diabetes Mellitus; Female; Heart Failure; Hemodynamics; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; Risk Factors; Stroke Volume; Ventricular Dysfunction, Right; Ventricular Function, Left

The epidemiological data of pulmonary hypertension (PH) due to left heart disease (LHD) are limited. This study investigated hemodynamic and clinical factors associated with mortality in patients with PH due to LHD.. We conducted a retrospective review in 243 patients with PH due to LHD, defined as mean pulmonary arterial pressure ≥25 mmHg and pulmonary wedge pressure >15 mmHg at rest in right heart catheterization. Kaplan-Meier and Cox proportional hazard regression analyses were performed. Seventy-five patients died during an average follow-up of 52 months (range, 20-73 months). On multivariate analysis, only diastolic pulmonary vascular pressure gradient (DPG) ≥7 mmHg among hemodynamic measurements was a predictor of mortality. Elevated N-terminal pro-brain natriuretic peptide (NT-pro BNP), more severe New York Heart Association (NYHA) class, anemia, and renal dysfunction were more strongly associated with mortality. Mean right atrial pressure (RAP) and currently available markers of pulmonary vascular remodeling including transpulmonary pressure gradient (TPG) and pulmonary vascular resistance (PVR) had no effect on survival.. DPG is weakly associated with mortality in PH due to LHD. Clinical factors such as NT-pro BNP, NYHA class, anemia and renal dysfunction are superior predictors. The prognostic ability of hemodynamic factors such as mean RAP, TPG, PVR and DPG is limited.

Topics: Aged; Blood Pressure; Disease-Free Survival; Female; Follow-Up Studies; Heart Diseases; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Survival Rate; Vascular Remodeling

Pulmonary arterial hypertension (PAH) prevalence has been reported to be between 0.5% and 17% in systemic lupus erythematosus (SLE). This study assessed PAH prevalence and predictors in an SLE cohort.. The Borg dyspnea scale, DLCO, N-terminal pro-brain natriuretic peptide (NT-proBNP), and Doppler echocardiographic (DE) were performed. An echocardiographic Doppler exercise test was conducted in selected patients. When DE systolic pulmonary arterial pressure was ≥ 45 mmHg or increased during exercise > 20 mmHg, a right heart catheterization was performed. Hemodynamic during exercise was measured if rest mean pulmonary arterial pressure was < 25 mmHg.. Of the 203 patients with SLE, 152 were included. The mean age was 44.9 ± 12.3 years, and 94% were women. Three patients had known PAH. The algorithm diagnosed 1 patient with chronic thromboembolic pulmonary hypertension and 5 with exercise-induced pulmonary artery pressure increase (4 with occult left diastolic dysfunction). These patients had significantly more dyspnea, higher NT-proBNP, and lower DLCO.. These data confirm the low prevalence of PAH in SLE. In our cohort, occult left ventricular diastolic dysfunction was a frequent diagnosis of unexplained dyspnea. Dyspnea, DLCO, and NT-proBNP could be predictors of pulmonary hypertension in patients with SLE.

Topics: Adult; Echocardiography, Doppler; Exercise Test; Female; Humans; Hypertension, Pulmonary; Lupus Erythematosus, Systemic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Risk Factors

We aimed to investigate plasma connective tissue growth factor (CTGF) levels in pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) (PAH-CHD) in children and the relationships of CTGF with hemodynamic parameters. Plasma CTGF levels were calculated in 30 children with CHD, 30 children with PAH-CHD and 25 health volunteers, using the subtraction method. Cardiac catheterization was performed to measure clinical hemodynamic parameters. Plasma CTGF levels were significantly higher in PAH-CHD than in those with CHD and health volunteers (p < 0.01). In cyanotic PAH-CHD, plasma CTGF levels were significantly elevated compared with acyanotic PAH-CHD in the same group (p < 0.05). Plasma CTGF levels showed positive correlation with B-type natriuretic peptide (BNP) in PAH-CHD (r = 0.475, p < 0.01), while oxygen saturation was inversely related to plasma CTGF levels (r = -0.436, p < 0.05). There was no correlation between CTGF and hemodynamic parameters. Even though the addition of CTGF to BNP did not significantly increase area under curve for diagnosis of PAH-CHD compared with BNP alone (p > 0.05), it revealed a moderately better specificity, positive predictive value and positive likelihood ratio than BNP alone. Plasma CTGF levels could be a promising diagnostic biomarker for PAH-CHD in children.

Topics: Area Under Curve; Biomarkers; Cardiac Catheterization; Case-Control Studies; Child; Child, Preschool; China; Connective Tissue Growth Factor; Female; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Infant; Male; Natriuretic Peptide, Brain; ROC Curve; Sensitivity and Specificity

Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

Topics: Animals; Arterial Pressure; Cardiovascular Agents; Disease Models, Animal; Fibrosis; Heart Ventricles; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Macrophages, Alveolar; Male; Monocrotaline; Myocytes, Cardiac; Natriuretic Peptide, Brain; Osteopontin; Pioglitazone; PPAR gamma; Pulmonary Artery; Rats, Sprague-Dawley; Thiazolidinediones; Vascular Remodeling; Ventricular Function, Right; Ventricular Remodeling

To report a case of secondary pulmonary arterial hypertension (PAH) and the relationship of intraocular pressure (IOP) change with right ventricular diameter (RVD) and brain natriuretic peptide (BNP).. Case report.. A 22-year-old woman with dilated and congested conjunctival and episcleral veins was diagnosed with high IOP. She was previously diagnosed with Sjögren syndrome and suffered from secondary PAH.. The RVD and BNP level improved and the IOP decreased with routine treatment for PAH. During self-cessation of treatment for PAH, the RVD, BNP level, and IOP deteriorated. However, they improved after treatment was reinitiated.. There was a synchronizing change in the parameters representing high pulmonary arterial pressure and IOP during treatment of PAH.

Topics: Antihypertensive Agents; Atrial Pressure; Conjunctiva; Diuretics; Drug Therapy, Combination; Female; Heart Ventricles; Humans; Hypertension, Pulmonary; Intraocular Pressure; Natriuretic Peptide, Brain; Ocular Hypertension; Sclera; Sjogren's Syndrome; Vasodilator Agents; Young Adult

We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43±8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the χ2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH.

Topics: Aged; Arteriovenous Fistula; C-Reactive Protein; China; Female; Humans; Hypertension, Pulmonary; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peritoneal Dialysis; Phosphorus; Prospective Studies; Risk Factors

Several studies have identified circulating biomarkers to be associated with the presence and severity of pulmonary arterial hypertension (PAH). Recent evidence supports a role for galectin-3 (Gal-3) and the mineralcorticoid aldosterone in left ventricular failure. However, studies on aldosterone together with Gal-3 in PAH are lacking.. We investigated a novel Aldosterone-galectin-3 (Gal-3) tandem and several other potential PAH biomarkers and their association with the disease severity.. A total of 57 patients, 41 with idiopathic PAH. (IPAH) and 16 with PAH associated with connective tissue disease (CTD), and 8 age-matched, non-relative controls were studied. Gal-3, aldosterone and other potential protein plasma concentrations were measured by single ELISA and multi-array MSD (Meso Scale Discovery) technology.. Gal-3 values were increased in both patients with IPAH (12.2±0.6 ng/mL; p<0.05) and with PAH-CTD (14.1±1.6 ng/mL; p<0.05) versus control (8.5±0.9 ng/mL), while aldosterone was significantly elevated in IPAH only (248.5±38.8 pg/mL vs control 71.9±18.2 pg/mL; p<0.05). In addition, aldosterone, Gal-3, and N-terminal pro-brain natriuretic peptide (NT-proBNP) values were all higher in patients in WHO functional class II-III versus PAH functional class I or controls. The vascular injury marker intercellular adhesion molecule 1 (ICAM-1) was increased in IPAH and PAH-CTD versus controls (559.5±18.2 pg/mL and 734.1±59.4 pg/mL vs controls 394.8±39.3 pg/mL, p<0.05, p<0.0001, respectively), whereas vascular cell adhesion molecule 1 (VCAM-1) and proinflammatory, anti-angiogenic interleukin-12 (IL-12) were elevated in PAH-CTD only (879.5±110.0 pg/mL and 391.2±70.3 pg/mL vs controls 489.8±44.6 pg/mL, p<0.01, and 102.1±15.2 pg/mL, p<0.01, respectively).. Heightened Gal-3 and aldosterone plasma concentrations in PAH patients indicate a role for Gal-3 signalling in the pathobiology of IPAH and PAH-CTD, and may serve as biomarkers for functional status and progression of disease.

Topics: Adult; Aged; Aldosterone; Biomarkers; Blood Proteins; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Galectin 3; Galectins; Humans; Hypertension, Pulmonary; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Severity of Illness Index; Up-Regulation

Recognizing heart disease is relevant to oncologists because cancer patients are at an increased risk of cardiac mortality due to shared risk factors and the adverse effects of cancer therapy. This study assessed the extent to which the measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) aids in the diagnosis of heart disease in addition to a history of coronary artery disease and the presence of atrial fibrillation (composite test). The NT- proBNP cutoff value was 100 pg/ml.. A series of 583 consecutive cancer patients (68.4 ± 11.0 years) who were referred because of cardiac or pulmonary symptoms prospectively underwent a diagnostic work-up. Heart disease was diagnosed if at least one of the following conditions was present: (a) history of coronary artery disease, (b) atrial fibrillation, (c) impaired left ventricular systolic function, (d) significant valvular disease, (e) pulmonary hypertension, or (f) left ventricular hypertrophy.. Except for (a), all 6 conditions were associated with NT-proBNP >100 pg/ml. The sensitivity/specificity values of the composite test were 0.92/0.50 for any heart disease. Several extracardiac covariates were associated with NT-proBNP >100 pg/ml, which contributed to the low test specificity.. The low specificity of NT-proBNP limits its value for the diagnosis of heart disease in cancer patients.

Topics: Adult; Aged; Atrial Fibrillation; Biomarkers; Coronary Artery Disease; Female; Heart Diseases; Heart Valve Diseases; Humans; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Predictive Value of Tests; Research Design; Sensitivity and Specificity; Ventricular Dysfunction, Left

Pulmonary arterial hypertension (PAH) is a major complication in renal failure patients, but very little information is available on the cardiovascular parameters in these patients. The prevalence and risk factors for PAH were systematically evaluated in patients with end-stage renal diseases (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD).. Between January 2010 and January 2014, 177 ESRD patients (85 males and 92 females) undergoing CAPD therapy were recruited. General data, biochemical parameters and echocardiographic findings were collected and PAH risk factors studied.. Study participants consisted of 65 patients (36.52%) with PAH (PAH group) and 112 patients without PAH (non-PAH group). The interdialytic weight gain, systolic blood pressure and diastolic blood pressure (DBP), mean arterial pressure and hypertensive nephropathy incidence in the PAH group were significantly higher than the non-PAH group (all p < 0.05). There were significant differences between PAH group and non-PAH group in C-reactive protein-positive rate, N-terminal pro-brain natriuretic peptide (NT-proBNP), hemoglobin, prealbumin and serum albumin levels (all p < 0.05). Compared with non-PAH group, PAH group showed significant increases in right ventricular internal diameter (RVID), right ventricular outflow tract diameter (RVOTD), main pulmonary artery diameter, left atrial diameter (LAD), left ventricular end-diastolic diameter, interventricular septal thickness, left ventricular mass index, early diastolic mitral annulus velocity and valve calcification incidence (all p < 0.05), and decreased left ventricular ejection fraction (LVEF), tricuspid annulus plane systolic excursion (TAPSE) and early diastolic blood flow peak and mitral annulus velocity (E/E') (all p < 0.05). Logistic regression analysis revealed that DBP, NT-proBNP, LAD, RVID, RVOTD, LVEF, TAPSE and E/E' are major risk factors for PAH.. We observed a high incidence of PAH in ESRD patients undergoing CAPD. Logistic regression analysis revealed that DBP, NT-proBNP, LAD, RVID, RVOTD, LVEF, TAPSE and E/E' are high-risk factors for PAH in ESRD patients undergoing CAPD.

Topics: Adult; Aged; China; Female; Humans; Hypertension, Pulmonary; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peritoneal Dialysis, Continuous Ambulatory; Prevalence; Risk Factors; Serum Albumin; Stroke Volume; Ventricular Dysfunction, Left

Exaggerated pulmonary pressor response to hypoxia is a pathgonomic feature observed in high altitude pulmonary edema (HAPE) susceptible mountaineers. It was investigated whether measurement of basal pulmonary artery pressure (Ppa) and brain natriuretic peptide (BNP) could improve identification of HAPE susceptible subjects in a non-mountaineer population. We studied BNP levels, baseline hemodynamics and the response to hypoxia (FIo2 = 0.12 for 30 min duration at sea level) in 11 HAPE resistant (no past history of HAPE, Control) and 11 HAPE susceptible (past history of HAPE, HAPE-S) subjects. Baseline Ppa (19.31 ± 3.63 vs 15.68 ± 2.79 mm Hg, p < 0.05) and plasma BNP levels (52.39 ± 32.9 vs 15.05 ± 9.6 pg/ml, p < 0.05) were high and stroke volume was less (p < 0.05) in HAPE-S subjects compared to control. Acute hypoxia produced an exaggerated increase in heart rate (p < 0.05), mean arterial pressure (p < 0.05) and Ppa (28.2 ± 5.8 vs 19.33 ± 3.74 mm Hg, p < 0.05) and fall in peripheral oxygen saturation (p < 0.05) in HAPE-S compared to control. Receiver operating characteristic (ROC) curves showed that Ppa response to acute hypoxia was the best variable to identify HAPE susceptibility (AUC 0.92) but BNP levels provided comparable information (AUC 0.85). BNP levels are easy to determine and may represent an important marker for the determination of HAPE susceptibility.

Topics: Adult; Altitude Sickness; Anthropometry; Blood Pressure; Case-Control Studies; Disease Susceptibility; Hemodynamics; Humans; Hypertension, Pulmonary; Hypoxia; Natriuretic Peptide, Brain; Pulmonary Artery; Respiratory Function Tests

Right ventricular function and biomarkers of B-type natriuretic peptide (BNP) and N-Terminal pro-BNP (NT pro-BNP) are used to determine the severity of right ventricular failure and outcomes from pulmonary hypertension. Real-time three-dimensional echocardiography (3DE) is a novel quantitative measure of the right ventricle and decreases the geometric assumptions from conventional two-dimensional echocardiography (2DE). We correlated right ventricular functional measures using 2DE and single-beat 3DE with biomarkers and hemodynamics to determine the severity of pediatric pulmonary hypertension.. We retrospectively evaluated 35 patients (mean age 12.67 ± 5.78 years) with established pulmonary hypertension who had echocardiograms and biomarkers on the same day. Ten out of 35 patients had hemodynamic evaluation within 3 days. 2DE evaluation included tricuspid annular plane systolic excursion (TAPSE), right ventricular myocardial performance index from tissue Doppler imaging (RV TDI MPI), and right ventricular fractional area change (FAC). Three-dimensional echocardiography evaluation included right ventricular ejection fraction (EF), end-systolic volume, and end-diastolic volume. The quality of the 3DE was graded as good, fair, or poor. Pearson correlation coefficients were utilized to evaluate between biomarkers and echocardiographic parameters and between hemodynamics and echocardiography.. Three-dimensional echocardiography and FAC correlated significantly with BNP and NT pro-BNP. TAPSE and RV TDI MPI did not correlate significantly with biomarkers. 3D right ventricular EF correlated significantly with hemodynamics. Two-dimensional echocardiography did not correlate with hemodynamics.. Single-beat 3DE is a noninvasive, feasible tool in the quantification of right ventricular function and maybe more accurate than conventional 2DE in evaluating severity of pulmonary hypertension.

Topics: Adolescent; Arterial Pressure; Biomarkers; Cardiac Catheterization; Child; Echocardiography, Doppler; Echocardiography, Three-Dimensional; Feasibility Studies; Female; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Pulmonary Artery; Retrospective Studies; Severity of Illness Index; Ventricular Dysfunction, Right; Ventricular Function, Right

B-type natriuretic peptide (BNP) has been shown to correlate with pulmonary hypertension (PH) in term neonates with persistent pulmonary hypertension of the newborn or congenital diaphragmatic hernia, and in very preterm infants with bronchopulmonary dysplasia. This study investigated the potential association of BNP and N-terminal-pro-BNP (NTproBNP) and PH within the first 72 hr of life in very preterm infants.. Preterm infants <32 weeks gestational age who received an echocardiogram within the first 72 hr of life were eligible. BNP and NTproBNP were sampled at the time of the echocardiogram. Right ventricular systolic pressure (RVSP) was calculated as a surrogate marker of PH. Simple and multiple linear regression analysis was performed to examine associations and potential confounding factors.. Sixty-one infants were included with a median (IQR) birth weight of 983 g (826-1,167) and a median (IQR) gestational age of 27(2) weeks (26(2) -28(6) ). There was no difference between BNP or NTproBNP levels for infants with or without measurable RVSP. There was no significant correlation of BNP and RVSP in multiple linear regression analysis (regression coefficient -0.0035 (95%CI: -0.020 to 0.013), P = 0.67). Also, NTproBNP and RVSP were not significantly correlated in multiple linear regression analysis (regression coefficient 0.0071 (95%CI: -0.019 to 0.033), P = 0.58).. B-type natriuretic peptides did not correlate with RVSP in the early postnatal period of very preterm infants. Pediatr Pulmonol. 2016;51:820-824. © 2016 Wiley Periodicals, Inc.

Topics: Biomarkers; Blood Pressure; Echocardiography; Female; Gestational Age; Humans; Hypertension, Pulmonary; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Systole

The purpose of this study was to evaluate the additional prognostic value of echocardiography in acute decompensation of advanced chronic heart failure (CHF), focusing on right ventricular (RV) dysfunction and its interaction with loading conditions. Few data are available on the prognostic role of echocardiography in acute HF and on the significance of pulmonary hypertension in patients with severe RV failure.. A total of 265 NYHA IV patients admitted for acute decompensation of advanced CHF (EF 22 ± 7%, systolic blood pressure 107 ± 20 mmHg) were prospectively enrolled. Fifty-nine patients met the primary composite endpoint of cardiac death, urgent heart transplantation, and urgent mechanical circulatory support implantation at 90 days. Pulmonary hypertension failed to predict events, while patients with a low transtricuspid systolic gradient (TR gradient <20 mmHg) showed a worse outcome [hazard ratio (HR) 2.37, 95% confidence interval (CI) 1.12-5.00, P = 0.02]. RV dysfunction [tricuspid annular plane systolic excursion (TAPSE) ≤14 mm] in the presence of a low TR gradient identified patients at higher risk of events (HR 2.97, 95% CI 1.19-7.41, P = 0.02). Multivariate analysis showed as best predictors of outcome low RV contraction pressure index (RVCPI), defined as TAPSE × TR gradient, and high estimated right atrial pressure (eRAP). Adding RVCPI (<400 mm*mmHg) and eRAP (≥20 mmHg) to conventional clinical (ADHERE risk tree and NT-proBNP) and echocardiographic risk evaluation resulted in an increase in net reclassification improvement of +19.1% and +20.1%, respectively (P = 0.01) and in c-statistic from 0.59 to 0.73 (P < 0.01).. In acute decompensation of advanced CHF, pulmonary hypertension failed to predict events. The in-hospital and short-term prognosis can be better predicted by eRAP and RVCPI.

Topics: Aged; Cardiovascular Diseases; Chronic Disease; Echocardiography; Emergencies; Female; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mortality; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Ventricular Dysfunction, Right

Glycosylated hemoglobin A1c (HbA1c) has been proposed as an independent predictor of long-term prognosis in pulmonary arterial hypertension. However, the clinical relevance of HbA1c in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) remains unknown. The aim of the present study was to investigate the clinical significance of HbA1c as a biomarker in CTEPH.. Prospectively, 102 patients underwent pulmonary endarterectomy (PEA) in our national referral center between March 2013 and March 2014, of which after exclusion 45 patients were analyzed. HbA1c- levels, hemodynamic and exercise parameters were analyzed prior and one-year post-PEA.. 45 patients (BMI: 27.3 ± 6.0 kg/m2; age: 62.7 ± 12.3 years) with a mean pulmonary arterial pressure (mPAP) of 43.6 ± 9.4 mmHg, a pulmonary vascular resistance (PVR) of 712.1 ± 520.4 dyn*s/cm5, a cardiac index (CI) of 2.4 ± 0.5 l/min/m2 and a mean HbA1c-level of 39.8 ± 5.6 mmol/mol were included. One-year post-PEA pulmonary hemodynamic and functional status significantly improved in our cohort. Baseline HbA1c-levels were significantly associated with CI, right atrial pressure, peak oxygen uptake and the change of 6-minute walking distance using linear regression analysis. However, using logistic regression analysis baseline HbA1c-levels were not significantly associated with residual post-PEA PH.. This is the first prospective study to describe an association of HbA1c-levels with pulmonary hemodynamics and exercise capacity in operable CTEPH patients. Our preliminary results indicate that in these patients impaired glucose metabolism as assessed by HbA1c is of clinical significance. However, HbA1c failed as a predictor of the hemodynamic outcome one-year post-PEA.

Topics: Aged; Arterial Pressure; Biomarkers; Chronic Disease; Cohort Studies; Endarterectomy; Female; Glycated Hemoglobin; Hemodynamics; Humans; Hypertension, Pulmonary; Immunoassay; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Pulmonary Artery

Childhood-onset pulmonary arterial hypertension (PAH) is considered complex and multifactorial, with relatively poor estimates of the natural history of the disease. Strategies allowing earlier detection, establishment of disease aetiology together with more accurate and sensitive biomarkers could enable better estimates of prognosis and individualise therapeutic strategies. Evidence is accumulating that genetic defects play an important role in the pathogenesis of idiopathic and hereditary forms of PAH. Altogether nine genes have been reported so far to be associated with childhood onset PAH suggesting that comprehensive multigene diagnostics can be useful in the assessment. Identification of disease-causing mutations allows estimates of prognosis and forms the most effective way for risk stratification in the family. In addition to genetic determinants the analysis of blood biomarkers are increasingly used in clinical practice to evaluate disease severity and treatment responses. As in genetic diagnostics, a multiplex approach can be helpful, as a single biomarker for PAH is unlikely to meet all requirements. This consensus statement reviews the current evidence for the use of genetic diagnostics and use of blood biomarkers in the assessment of paediatric patients with PAH.

Topics: Activin Receptors, Type II; Adolescent; Antigens, CD; Atrial Natriuretic Factor; Biomarkers; Bone Morphogenetic Protein Receptors; C-Reactive Protein; Caveolin 1; Child; Consensus; Disease Management; Endoglin; Endothelial Cells; Endothelins; Familial Primary Pulmonary Hypertension; Galectin 3; Genetic Testing; Growth Differentiation Factor 15; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Potassium Channels, Tandem Pore Domain; Prognosis; Protein Serine-Threonine Kinases; Receptor, Notch3; Receptors, Cell Surface; Receptors, Notch; Smad8 Protein; Troponin T; Uric Acid

Biphasic cuirass ventilation (BCV) is a form of non-invasive extrathoracic positive and negative pressure mechanical ventilation. The present study was conducted to quantify our positive experience using BCV to dramatically improve gas exchange and cardiac function in patients with acute exacerbation of chronic respiratory failure and secondary pulmonary hypertension (PH).. BCV was applied for 2 weeks in 17 patients with PH caused by lung disease. Ventilation sessions were limited to 1 h per day to prevent exhaustion. To assess respiratory and circulatory effects, percutaneous arterial oxygen saturation (SpO2) was measured before and after each daily BCV session, and right heart catheter test [mean pulmonary artery pressure (mPAP), right atrium pressure (RAP), pulmonary artery occlusion pressure (PAOP) and cardiac index (CI)] and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured before and after a series of BCV sessions.. SpO2 transiently improved after each BCV session. After a series of BCV, mPAP decreased from 27.2 to 22.4 mmHg (p = 0.0007). PAOP, CI and serum NT-proBNP levels decreased compared with baseline. No patients were treated with epoprostenol, iloprost, bosentan or sildenafil for PH.. BCV may improve circulatory function in patients with PH caused by lung disease.

Topics: Aged; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Gas Exchange; Respiration, Artificial; Respiratory Insufficiency

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; CD146 Antigen; Echocardiography; Female; France; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mitral Valve Stenosis; Natriuretic Peptide, Brain; Prospective Studies; Severity of Illness Index

To investigate the incidence and risk factors of pulmonary hypertension (PH) in patients with chronic kidney disease (CKD).. 86 patients (53% men, 47% women; mean age, 45±13 years) with nondiabetic CKD were examined. According to the magnitude of glomerular filtration rate (GFR) decrease, all the patients were divided into 3 groups: 1) 33 patients with a GFR of 89--45 ml/min; 2) 33 with a GFR of 44--15 ml/min; 3) 20 with a GFR of <15 ml/min who were treated with hemodialysis. A control group consisted of 20 individuals with preserved kidney function (a GFR of >90 ml/min). Physical examination and transthoracic echocardiography were performed in all the patients. The serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNT) and cystatin C were determined.. PH was detected in 21 (24.4%) of the 86 patients with CKD. As CKD progressed, its prevalence in Groups 1, 2, and 3 increased, amounting to 18.2, 24.2, and 35%, respectively. The most predictably significant risk factors for PH were hypertension (ρ=0.35; р=0.001) and kidney dysfunction (creatinine (ρ=0.23; р=0.02). Elevated pulmonary artery systolic pressure (PASP) correlated with right ventricular (RV) dimension index (ρ=0.45; р<0.0001), right atrial volume index (ρ=0.3; р=0.02), left atrial volume index (ρ=0.3; р=0.009), and left ventricular mass index (ρ=0.35; р=0.03). In all the patients with CKD in the presence of PH, the NT-proBNP level was significantly higher than in its absence: 37.43 (5.83; 59.84) and 8.54 (5.1; 20.43) fmol/ml, respectively (р=0.01). Positive correlations were found between the level of cystatin C and the presence of PH (ρ=0.32; р=0.003). Analysis of the ROC curve (AUC=0.718; р=0.03) in the predialysis-stage CKD groups (n=66) revealed that the cystatin C level of > 1045 ng/ml with a sensitivity of 71% and a specificity of 60% suggested that PH was present. Multivariate analysis showed that the factors correlating with the presence of PH were NT-proBNP (β=0.34; р=0.008) and RV dimension index (β=0.3; р=0.002).. EchoCG reveals PH in almost 25% of the patients with CKD, which occurs at its predialysis stage. Elevated PASP is associated with myocardial structural changes. Traditional risk factors (hypertension) and diminished kidney function affect the development of PH.. Цель исследования. Изучение частоты и факторов риска развития легочной гипертонии (ЛГ) у больных хронической болезнью почек (ХБП). Материалы и методы. Обследовали 86 больных ХБП недиабетической этиологии (53% мужчин, 47% женщин, средний возраст 45±13 лет). В зависимости от степени снижения скорости клубочковой фильтрации (СКФ) всех больных разделили на 3 группы. В 1-ю группу включили 33 пациентов с СКФ 89-45 мл/мин, во 2-ю группу - 33 больных с СКФ 44-15 мл/мин, в 3-ю группу - 20 больных со СКФ <15 мл/мин, получающих лечение гемодиализом. Контрольную группу составили 20 лиц с сохранной функцией почек (СКФ >90 мл/мин). Всем проведено общеклиническое обследование и трансторакальная эхокардиография. Определяли концентрацию N-концевого предшественника натрийуретического пептида (NT-proBNP) и цистатина С в сыворотке крови. Результаты. ЛГ выявлена у 21 (24,4%) из 86 пациентов с ХБП. По мере прогрессирования ХБП ее распространенность в 1, 2 и 3-й группах нарастала, составляя 18,2, 24,2 и 35% соответственно. Наиболее прогностически значимыми факторами развития ЛГ были артериальная гипертония - АГ (ρ=0,35; р=0,001) и нарушение функции почек (креатинин ρ=0,23; р=0,02). Повышение систолического давления в легочной артерии (СДЛА) коррелировало с индексом размера правого желудочка - ПЖ (ρ=0,45; р<0,0001), индексом объема правого предсердия (ρ=0,3; р=0,02), индексом объема левого предсердия (ρ=0,3; р=0,009), индексом массы миокарда левого желудочка (ρ=0,35; р=0,03). У всех пациентов с ХБП при ЛГ уровень NT-proBNP был достоверно выше, чем в ее отсутствие, - 37,43 (5,83; 59,84) и 8,54 (5,1; 20,43) фмоль/мл соответственно (р=0,01). Обнаружены положительные корреляции между уровнем цистатина С и наличием ЛГ (ρ=0,32; р=0,003). При анализе ROС-кривой (AUC=0,718; р=0,03) в группах с додиализными стадиями ХБП (n=66) уровень цистатина С >1045 нг/мл с чувствительностью 71% и специфичностью 60% свидетельствовал о наличии ЛГ. При многофакторном анализе факторами, коррелирующими с наличием ЛГ, были NT-proBNP (β=0,34; р=0,008) и индекс размера ПЖ (β=0,3; р=0,002). Заключение. По данным ЭхоКГ ЛГ выявляется почти у 25% больных ХБП, возникая на додиализной стадии. Повышение СДЛА сопряжено со структурными изменениями миокарда. На развитие ЛГ влияют традиционные факторы риска (АГ) и снижение функции почек.

Topics: Adult; Creatinine; Cystatin C; Echocardiography; Female; Glomerular Filtration Rate; Humans; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; ROC Curve

We investigated the relationship of left ventricular (LV) diastolic dysfunction and LV mass index (LVMI) against pulmonary hypertension (PH) in systemic autoimmune disease (SAD).. A total of 84 SAD patients (68 females; 53±17years; systemic lupus erythematosus, 27%; scleroderma, 17%; vasculitis, 16%; mixed connective tissue disease, 13% and polymyositis/dermatomyositis complex, 10%) without significant pericardial effusion (PE) on TTE (Vivid E9, GE) were analyzed. On TTE, PH was defined as peak tricuspid regurgitation velocity (TRV) of ≥2.9m/s based upon 2015 ESC guideline. Left atrial volume index (LAVI) and E/E' were measured as indicators of LV diastolic dysfunction. LVMI was also measured.. Seven patients (8%) had PH. PH patients had greater LAVI (p<0.001), E/E' (p=0.004), LVMI (p=0.009) than non-PH patients. LAVI (R=0.458), E/E' (R=0.337), and LVMI (R=0.313) significantly and positively correlated with TRV (all p<0.05). Multiple regression analysis was performed to explore determinants of TRV. Age, female sex, and brain natriuretic peptide (BNP) were included in all the models. Three multiple regression models were generated using 1) LAVI, 2) E/E', and 3) LVMI and included LAVI, E/E', LVMI, and BNP as significant variables influencing TRV. Multi logistic regression analysis for predicting TRV of ≥2.9m/s showed that LAVI, and E/E' were significant predictors (Odds ratio, 1.296, and 1.370, respectively).. In SAD patients without PE, LV diastolic dysfunction and increment of LVMI was closely associated with PH based upon TRV. LAVI and E/E' were independent predictors for PH. Measuring LAVI and E/E' may be a key to determine the mechanism of PH in these patients.

Topics: Age Factors; Autoimmune Diseases; Female; Heart Atria; Humans; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Size; Pericardial Effusion; Retrospective Studies; Severity of Illness Index; Sex Factors; Statistics as Topic; Tricuspid Valve Insufficiency; Ventricular Dysfunction, Left

Topics: Adult; Aged; Biomarkers; Female; Heart Ventricles; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Ventricular Dysfunction, Left

Topics: Biomarkers; Bronchopulmonary Dysplasia; Chitinase-3-Like Protein 1; Demography; Female; Humans; Hypertension, Pulmonary; Infant, Extremely Premature; Male; Natriuretic Peptide, Brain; Pulmonary Ventilation; Risk Factors; Troponin I

To study the serum level of carbohydrate antigen 125 (CA125) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and its relation with pulmonary hypertension.. Forty-six patients with AECOPD complicated by pulmonary hypertension, 46 with AECOPD and 38 healthy control subjects were examined for their clinical data, pulmonary function, echocardiographic findings, and serum levels of lung tumor markers and brain natriuretic peptide (BNP).. Compared with the healthy control group, COPD patients with or without pulmonary hypertension showed significantly decreased pulmonary function (P<0.05), especially in those with AECOPD and concurrent pulmonary hypertension (P<0.05). Serum CA125 level was obviously higher in AECOPD group than in the healthy control group, and further increased in AECOPD patients with pulmonary hypertension (P<0.05). The levels of lung tumor markers (CEA, NSE, CYFRA and PROGRP) were similar among the 3 groups (P>0.05). The serum level of BNP in patients with AECOPD and concurrent pulmonary hypertension was significantly higher than that in patients with AECOPD (P<0.05). Pearson linear correlation analysis showed that serum CA125 was positively correlated with pulmonary artery systolic pressure and BNP in AECOPD patients with pulmonary hypertension (P<0.01).. Serum CA125 may serve as a serological index to identify AECOPD patients with pulmonary hypertension.

Topics: Acute Disease; Biomarkers, Tumor; CA-125 Antigen; Case-Control Studies; Disease Progression; Humans; Hypertension, Pulmonary; Lung; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive

Endoplasmic reticulum (ER) stress contributes to pulmonary artery hypertension (PAH). However, the exact roles of ER stress in right ventricular (RV) dysfunction, which is strongly associated with PAH, are largely unknown. Here, we aimed to explore how ER stress affects RV function in a rat PAH model and evaluated the effects of an ER stress inhibitor on RV dysfunction.. We examined expression changes of an ER marker: chaperone glucose-regulated protein 78 (GRP78), three ER stress sensor proteins: activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1), and protein kinase RNA-like endoplasmic reticulum kinase (PERK), and a key ER stress-induced apoptosis indicator: CCAAT/enhancer-binding protein homologous protein (CHOP), with inflammation indicators: interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and matrix metalloproteinases (MMPs) in RV at 3, 7, 14 and 28 days following a single dose of monocrotaline (MCT) injection, with or without a preventive treatment [4-phenylbutyric acid (PBA)]. RV function was evaluated by histological, molecular and echocardiographic analysis.. 1) GRP78 protein expression started to increase (1.5 ± 0.06 fold change) at 3d post MCT injection, even before the formation of PAH. 2) ATF6, IRE1, and PERK showed distinctive expression patterns post MCT injection. 3) CHOP expression remained low at day 3 & 7, but significantly increased at day 14 (p < 0.05), along with the peak of RV cardiomyocytes apoptosis. 4) PBA inhibited ER stress and alleviated remodeling and dysfunction in the RV.. The early phase of ER stress might benefit RV function, whereas the extended phase led to RV cardiomyocyte apoptosis and dysfunction. Inhibition of ER stress by PBA during PAH directly improved RV function.

Topics: Activating Transcription Factor 6; Animals; Apoptosis; eIF-2 Kinase; Endoplasmic Reticulum Stress; Heart Ventricles; Heat-Shock Proteins; Hypertension, Pulmonary; Male; Membrane Proteins; Monocrotaline; Myocytes, Cardiac; Natriuretic Peptide, Brain; Peptide Fragments; Phenylbutyrates; Protein Serine-Threonine Kinases; Rats, Sprague-Dawley; RNA, Messenger; Transcription Factor CHOP; Ventricular Dysfunction, Right

Pulmonary hypertension (PH) is a feared complication in patients with sarcoidosis.It is an important negative prognostic factor which is reflected as a priority given to these subjects for orthotopic lung transplantation. We evaluated the relationship between BNP, 6MWD test, DLCO% values and the severity of sarcoidosis-associated pulmonary hypertension.. A retrospective chart review was conducted between January 2010 and January 2015 on consecutive confirmed adult subjects diagnosed with sarcoidosis. Demographics, medical comorbidities, clinical features, pulmonary function tests (PFTs), 6MWD test, transthoracic echocardiography, laboratory investigations, radiographic findings, treatment and outcome data were collected from medical records. Subjects with suspicion for PH (i.e. those with PASP ≥ 25 mmHg) were included in the study. PH severity was classified using PASP into mild (PASP 25-49 mmHg), moderate (50-69 mmHg) and severe (≥70 mmHg). We evaluated the strength of correlation between BNP, 6MWD test, DLCO% and the severity of PH. The association between variables was performed using Pearson correlation coefficient and results were considered statistically significant if P value was <0.05.. Among the 108 cases diagnosed with sarcoidosis, we identified a total of 27 patients (25%) who had an elevated PASP suggestive of PH and met the study inclusion criteria. There was a significant correlation between BNP level (r=0.804, P=0.003), 6MWD test (r=-0.865, P=0.000), DLCO% (r=-0.513, P=0.015) and the PASP in sarcoidosis patients.. Although these simple tests should not be used as screening tools for suspecting sarcoidosis-associated pulmonary hypertension, they may be of value in following its progression in subjects already diagnosed with pulmonary hypertension.

Topics: Aged; Biomarkers; Disease Progression; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Pulmonary Diffusing Capacity; Retrospective Studies; Sarcoidosis, Pulmonary; Severity of Illness Index; Time Factors; Walking

To estimate the point prevalence of pulmonary hypertension (PH) and determine the associated factors for PH in patients with systemic lupus erythematosus (SLE).. A prospective cross-sectional study of 114 patients with SLE was conducted in a single tertiary center. Transthoracic echocardiography was performed to estimate the pulmonary arterial pressures. PH was defined as resting systolic pulmonary artery pressure (sPAP) ≥ 40 mmHg, in the absence of left heart disease.. PH was identified in nine patients (7.9%) who had few cardiopulmonary symptoms. SLE patients with PH had higher SLE disease activity index score. In particular, serum uric acid (UA) was significantly higher in patients with PH than in those without PH. In multivariate analysis, UA remained significant for the presence of PH. Moreover, serum UA level correlated significantly with plasma NT-pro-B-type natriuretic peptide level as well as sPAP. At the cutoff level of 6.5 mg/dL, serum UA had reasonable accuracy for predicting the presence of PH in SLE patients (sensitivity 66.7% and specificity 96.2%).. A significant number of SLE patients in rheumatology practice have undiagnosed PH with few discernible symptoms. Serum UA level may be useful as a surrogate marker for screening of PH in patients with SLE.

Topics: Adult; Biomarkers; Blood Pressure; Comorbidity; Cross-Sectional Studies; Echocardiography; Female; Humans; Hypertension, Pulmonary; Lupus Erythematosus, Systemic; Mass Screening; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prospective Studies; Sensitivity and Specificity; Uric Acid

Topics: Aged; Echocardiography; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Admission

The value of echocardiography in assessing disease severity and predicting outcome in pediatric pulmonary arterial hypertension (PAH) is insufficiently defined. The aim of this study was to describe correlations between echocardiography and disease severity and outcome in pediatric PAH.. Forty-three consecutive children (median age, 8.0 years; range, 0.4-21.5) with idiopathic/hereditary PAH (n=25) or PAH associated with congenital heart disease (n=18) were enrolled in a prospective single-center observational study. Anatomic and right ventricular-functional variables were obtained by two-dimensional echocardiography and Doppler-echocardiography at presentation and at standardized follow-up and were correlated with measures of disease severity (World Health Organization functional class [WHO-FC], N-terminal-pro-B-type natriuretic peptide, hemodynamics) and lung-transplantation-free survival. Right atrial and right ventricular dimensions correlated with WHO-FC and hemodynamics (P<0.05), whereas left ventricular dimensions correlated with hemodynamics and survival (P<0.05). Right-to-left ventricular dimension ratiocorrelated with WHO-FC, hemodynamics and survival (P<0.05). Right ventricular ejection time correlated with hemodynamics and survival (P<0.05) and tended to correlate with WHO-FC (P=0.071). Tricuspid annular plane systolic excursion correlated with WHO-FC, mean right atrial pressure and survival (P<0.05).. This early descriptive study shows that echocardiographic chararacteristics of both the right and the left heart correlate with disease severity and outcome in pediatric PAH, both at presentation and during the course of the disease. The preliminary data from this study support the potential value of echocardiography as a tool in guiding management in children with PAH.

Topics: Adolescent; Age Factors; Atrial Function, Right; Atrial Pressure; Biomarkers; Child; Child, Preschool; Disease Progression; Echocardiography, Doppler; Familial Primary Pulmonary Hypertension; Female; Heart Defects, Congenital; Heart Ventricles; Humans; Hypertension, Pulmonary; Infant; Kaplan-Meier Estimate; Lung Transplantation; Male; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Factors; Severity of Illness Index; Stroke Volume; Time Factors; Tricuspid Valve; Ventricular Function, Left; Ventricular Function, Right; Young Adult

Topics: Adult; Anemia, Sickle Cell; Biomarkers; Blood Flow Velocity; Cohort Studies; Echocardiography; Humans; Hypertension, Pulmonary; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Tricuspid Valve; Ultrasonography, Doppler; Young Adult

Pediatric pulmonary arterial hypertension (PAH) presents certain specific features. In this specific age group, experimental models to study the pathophysiology of PAH are lacking. To characterize hemodynamic, morphometric, and histological progression as well as the expression of neurohumoral factors and regulators of cardiac transcription in an infantile model of PAH induced by monocrotaline (MCT), eight-day-old Wistar rats were randomly injected with MCT (30 mg/kg, sc, n = 95) or equal volume of saline solution (n = 92). Animals were instrumented for biventricular hemodynamic recording 7, 14, and 21 days after MCT, whereas samples were collected at 1, 3, 7, 14, and 21 days after MCT. Different time point postinjections were defined for further analysis. Hearts and lungs were collected for morphometric characterization, assessment of right- and left-ventricle (RV and LV) cardiomyocyte diameter and collagen type-I and type-III ratio, RV collagen volume fraction, and pulmonary vessels wall thickness. mRNA quantification was undertaken for brain natriuretic peptide (BNP), endothelin-1 (ET-1), and for cardiac transcription regulators (HOP and Islet1). Animals treated with MCT at the 8th day of life presented RV hypertrophy since day 14 after MCT injection. There were no differences on the RV collagen volume fraction or collagen type-I and type-III ratio. Pulmonary vascular remodelling and PAH were present on day 21, which were accompanied by an increased expression of BNP, ET-1, HOP, and Islet1. The infantile model of MCT-induced PAH can be useful for the study of its pathophysiology and to test new therapeutic targets in pediatric age group.

Topics: Animals; Animals, Newborn; Collagen Type I; Collagen Type III; Disease Models, Animal; Endothelin-1; Female; Heart; Hemodynamics; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lung; Male; Monocrotaline; Myocytes, Cardiac; Natriuretic Peptide, Brain; Pyrrolizidine Alkaloids; Rats; Rats, Wistar; RNA, Messenger; Time Factors; Transcription Factors

This study evaluated the role of echocardiography and BNP in patients with interstitial lung disease (ILD), to identify those with PH and RV dysfunction. The aims of this study were: 1-to evaluate the accuracy of an algorithm including BNP, DLCO and echocardiographic measurements to identify PH and RV dysfunction; 2- to evaluate BNP and Echo values concordance in relation to right catheterization measurement.. We analyzed 113 patients with diagnosis of ILD. Echo examination included: Pulmonary systolic, diastolic and mean Arterial Pressure (PAPs, PAPd, PAP mean), End-Diastolic and End-Systolic right ventricle diameters, Inferior Caval Vein diameter, and Tricuspid Annular Plane Systolic Excursion (TAPSE). Patients revealing increased PAPs at echocardiography underwent to catheterization.. Patients with PAPs > 40 mm Hg (37 patients), PAPmean ≥ 25 mm Hg (23 patients) and PAPd ≥ 20 mm Hg showed BNP increased (157 ± 96 vs 16 ± 14 pg/ml p = 0.004; 201 ± 120 vs 28 ± 17 pg/mL; 124 ± 88 vs 23 ± 18 pg/ml p < 0.001) as patients with TAPSE ≤16 mm (25 patients) (145 ± 104 vs 26 ± 21 pg/ml p < 0.001). In catheterized patients (37 patients) BNP was increased in patients with invasive PAPs > 40 mm Hg (165 ± 112 vs 29 ± 14 pg/ml p < 0.02), as well as in patients with Wedge pressure > 14 mm Hg (199 + 153 vs 54 + 39 pg/mL; p = 0.01). ROC Curve analysis showed that elevated values of BNP, PAPs, PAP mean are able to assess PH. On the other hand, lower values of DLCO (<40%) and TAPSE (≤16 mm) detect PH. Logistic regression analysis of the previous parameters, confirmed their diagnostic role in PH detection.. In patients with ILD, an algorithm including BNP, DLCO and echocardiography could be useful for non invasive screening of PH.. ARTEMIS-HP trial; ID number: NCT00879229.

Topics: Aged; Algorithms; Biomarkers; Diagnosis, Differential; Echocardiography, Doppler; Female; Humans; Hypertension, Pulmonary; Italy; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Selection; Prevalence; Retrospective Studies; Risk Factors; Severity of Illness Index; Tertiary Care Centers

B-type natriuretic peptide (BNP), an established biomarker of ventricular pressure overload, is used in the assessment of children with pulmonary hypertension (PH). PH is commonly observed in congenital diaphragmatic hernia (CDH). However, the use of BNP levels to guide treatment in this patient population has not been well defined. In this study, we investigate BNP levels in a large cohort of CDH patients treated at a single institution.. We retrospectively reviewed charts of all CDH patients enrolled in our pulmonary hypoplasia program from 2004-2013. PH was assessed by echocardiography using defined criteria, and patients were further stratified into the following cohorts: no PH, short-term PH (requiring nitric oxide but no additional vasodilatory therapy), long-term PH (requiring continued vasodilatory therapy post-discharge), and ECMO (requiring ECMO therapy).. A total of 132 patients were studied. BNP levels were significantly increased in patients with PH compared to patients with normal pulmonary pressures (P<0.01). BNP levels were not significantly different between the ST-PH, LT-PH, and ECMO cohorts, but all levels in all three cohorts were significantly increased compared to patients who did not develop PH.. Our findings indicate that plasma BNP levels correlate with pulmonary hypertension as well as the requirement for ECMO in CDH patients. Monitoring of serial BNP levels may provide a useful prognostic tool in the management of CDH.

Topics: Extracorporeal Membrane Oxygenation; Female; Hernias, Diaphragmatic, Congenital; Herniorrhaphy; Humans; Hypertension, Pulmonary; Infant, Newborn; Male; Monitoring, Intraoperative; Natriuretic Peptide, Brain; Retrospective Studies; Ventricular Pressure

Plasma amino acid concentrations (aminogram) show distinct patterns under various pathologic conditions. However, the plasma aminogram pattern in patients with pulmonary hypertension (PH) has not been elucidated. We sought to examine whether an aminogram could be predictive of clinical severity in patients with PH. We attained fasting plasma aminograms for 140 patients with PH and then compared the patient plasma amino acid levels with those of age- and gender-matched healthy control subjects. Aminograms revealed that the plasma concentrations of many amino acids were significantly different between patients with PH and healthy control subjects. We focused on the Fischer ratio (branched-chain amino acids/aromatic amino acids) as an integrated parameter. In all enrolled patients, Fischer ratio was negatively correlated with New York Heart Association functional class (ρ = -0.37, p <0.001), plasma B-type natriuretic peptide (ρ = -0.35, p <0.001), and pulmonary vascular resistance (ρ = -0.27, p = 0.002) and positively correlated with venous oxygen saturation (ρ = 0.27, p = 0.002) and 6-minute walk distance (ρ = 0.23, p = 0.016). Time course changes in Fischer ratio and in cardiac output were significantly correlated (ρ = 0.39, p = 0.024). The aminogram is changed in patients with PH, and in these patients, Fischer ratio decreases in proportion to the clinical severity of PH.

Topics: Adult; Aged; Amino Acids; Biomarkers; Case-Control Studies; Female; Hospitals, University; Humans; Hypertension, Pulmonary; Inpatients; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity; Severity of Illness Index

International guidelines do not provide strong recommendations on the duration and intensity of follow-up after acute pulmonary embolism (PE), nor on screening-programs for chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to address this gab by performing an external validation of the easy "CTEPH rule-out-criteria" based on a normal NT-proBNP level and the absence of 3 ECG characteristics.. 134 patients underwent clinical follow-up 6months after PE. Predefined transthoracic echocardiographic (TTE) criteria were used to categorize patients as "PH unlikely" or "PH possible/likely". The latter patients underwent further (invasive) diagnostic procedures to confirm and classify the diagnosis of pulmonary hypertension. NT-proBNP and ECGs, both assessed at the day of echocardiography, were evaluated post-hoc.. Sixty-three patients (47%) scored none of the "CTEPH rule-out criteria" positive, of whom 61 had normal TTE (97%). Twenty-five patients (19%) were categorized by TTE as "PH possible/likely"; of those, 6 were diagnosed with CTEPH. The sensitivity of rule-out criteria for CTEPH was 100% (95%CI 56-100%; 6/6 patients identified), and for "PH possible/likely" on TTE 92% (95%CI 74-99%; 23/25 patients identified): 2 asymptomatic patients with estimated systolic pulmonary arterial pressure of 36mmHg and 38mmHg, respectively, who remained stable during further 2-year follow-up, were not identified. Inter-observer agreement for the adjudication of the ECG characteristics was excellent (kappa-statistic 0.97).. In this external validation cohort, we confirmed the diagnostic accuracy and reproducibility of the "CTEPH rule-out criteria". These results provide a solid ground for future outcome trials applying this algorithm.

Topics: Adult; Aged; Algorithms; Chronic Disease; Cohort Studies; Decision Support Systems, Clinical; Diagnosis, Computer-Assisted; Echocardiography; Female; Humans; Hypertension, Pulmonary; Male; Mass Screening; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Reproducibility of Results; Sensitivity and Specificity; Thromboembolism; Troponin T

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Exercise Tolerance; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Protein Precursors; Retrospective Studies; Spain; Time Factors; Young Adult

Topics: Clinical Trials, Phase III as Topic; Disease Progression; Dyspnea; Endpoint Determination; Exercise Test; Guanylate Cyclase; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Pyrazoles; Pyrimidines; Randomized Controlled Trials as Topic; Vascular Resistance; Walking; World Health Organization

Pulmonary hypertension (PH) frequently complicates the course of idiopathic pulmonary fibrosis (IPF) patients and is associated with significantly worse outcomes. The aim of the present study was to investigate the incidence of PH in IPF patients and evaluate the correlation between clinical parameters and systolic pulmonary artery pressure (sPAP).. Hospitalized patients with IPF, who were evaluated for sPAP by Doppler echocardiography from January 2004 to December 2011, were enrolled in our study. Patients were defined as PH by an estimated sPAP > 50 mmHg and graded as PH likely, PH possible and PH unlikely, based on the 2009 European Society of Cardiology/European Respiratory Society PH Guidelines. The correlations between clinical parameters and sPAP were analyzed by multiple linear regression.. Totally, 119 IPF patients were enrolled in our study and 28 (23.5%), 20 (16.8%) and 71 (59.7%) patients were PH likely, PH possible and PH unlikely, respectively. Borg dyspnea score was positively correlated with sPAP, r = 0.467, P < 0.001. Oxygen saturation was negatively correlated with sPAP, r = -0.416, P < 0.001. Diffusing capacity of the lung for carbon monoxide percentage predicted was negatively correlated with sPAP, r = -0.424, P = 0.003. N-terminal fragment of pro-brain natriuretic peptide and pulmonary artery width was positively correlated with sPAP, r = 0.452, P = 0.011 and r = 0.513, P < 0.001, respectively.. The incidence of PH in IPF patients was 23.5% in a single center of China. PH may worsen the dyspnea, right heart dysfunction and decrease the life quality of the patients with IPF.

Topics: Aged; Echocardiography, Doppler; Female; Humans; Hypertension, Pulmonary; Idiopathic Pulmonary Fibrosis; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Smoking

Increased extravascular lung water (EVLW) is seen as B-lines on chest ultrasonography. In lowlanders ascending to altitude the time course, relationship with the patient's clinical status and factors affecting B-lines are still unclear. The aim was to monitor B-lines, clinical status and N-terminal B-type natriuretic peptide (NT-proBNP) during exposure to high altitude.. Chest ultrasonography, blood samples, cardiovascular parameters, and signs and symptoms of high altitude pulmonary oedema (HAPE) were prospectively assessed in 19 participants at baseline and after ascent to 3830 m (9, 24, 48, 72 h, and 8 days) by blinded investigators. Potential confounding factors (e.g. altitude variations, physical effort) were minimized. Generalized estimating equations were used to analyse factors associated with B-lines. B-lines changed with exposure to altitude (P = 0.006) in a parabolic-like pattern within the first 72 h; 10 of 18 participants (55.6%) had >5 B-lines at 24 h. B-lines were correlated with the number of signs and symptoms (partial coefficient = 0.372, P = 0.001). B-lines were associated with time (P = 0.038), sex (P = 0.013), and SpO2 (P = 0.042), but not with NT-proBNP (P = 0.546). The participant with a clinical diagnosis of HAPE had 23 B-lines.. B-lines during exposure to altitude seem to reflect the individual response to hypobaric hypoxia and represent clinically relevant alterations at high altitude, also in patients with HAPE. Similar to previous studies, our results support a non-cardiogenic aetiology of B-lines.

Topics: Adult; Altitude Sickness; Biomarkers; Female; Heart Rate; Humans; Hypertension, Pulmonary; Hypoxia; Italy; Male; Natriuretic Peptide, Brain; Oximetry; Peptide Fragments; Prospective Studies; Respiratory Rate; Ultrasonography

When a forward running pressure wave from the right ventricle reaches the narrow vessels in the pulmonary circulation, it is reflected as a backward running wave. We aimed to relate changes in right ventricular waveform reflection (RVWR) to changes in clinical variables in pulmonary arterial hypertension (PAH) patients.. Twenty-one PAH patients with RV waveform recordings from two sequential catheterisations at least 6 months apart were included. Six-minute walked distance (6MWD) and brain natriuretic peptide (BNP) level were also available. RVWR was defined as 'the pressure from the inflection point on the upstroke RV pressure wave to RV peak pressure'. Direction of change in RVWR, 6MWD and BNP was classified as (+) if increased and (-) if decreased. Spearman correlations were used to analyse the relation between changes. Pearson's correlation coefficient was used to analyse relation between RVWR and pulmonary vascular resistance (PVR).. The correlation between change in RVWR and 6MWD was - 0.67 (p < 0.01) and between RVWR and BNP was - 0.53 (p < 0.05). Actual RVWR and PVR correlated both at first (0.56, p < 0.001) and at second right heart catheterisation (0.45, p < 0.001).. RVWR might have clinical implications indicating a change in clinical status and disease progression in patients with PAH.

Topics: Adult; Arterial Pressure; Biomarkers; Cardiac Catheterization; Disease Progression; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Pulmonary Artery; Time Factors; Vascular Resistance; Ventricular Function, Right; Ventricular Pressure

Gremlin-1, an intrinsic antagonist of bone morphogenetic protein (BMP) signaling, has been implicated in the pathophysiology of pulmonary arterial hypertension (PAH). However, it is unknown whether gremlin-1 can be detected in the circulation of PAH patients and whether it is associated with patients' functional status and outcome. With a mean level of 242 ± 24 ng/ml, gremlin-1 levels of 31 PAH patients were significantly elevated compared to 151 ± 18 ng/ml in 15 age- and gender-matched healthy subject (p = 0.016). In PAH patients, increasing gremlin-1 levels correlated with N-terminal prohormone of brain natriuretic peptide levels (r = 0.608, p < 0.001) and inversely with the 6-minute walking distance (r = -0.412, p = 0.029). Furthermore, gremlin-1 significantly stratified survival in PAH patients (p = 0.015). Gremlin-1 may represent a new biomarker for PAH which can be linked directly to the underlying pathomechanism. Elevated levels of gremlin-1 are associated with patients' functional status and survival, thus gremlin-1 neutralization could represent a potential therapeutic strategy to increase BMPR2 signaling.

Topics: Aged; Biomarkers; Bone Morphogenetic Proteins; Case-Control Studies; Exercise Test; Female; Glomerular Filtration Rate; Humans; Hypertension, Pulmonary; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Signal Transduction; Survival Rate; Walking

High altitude (HA) pulmonary edema (PE) results from complex and misunderstood interactions between adaptation mechanisms. We assessed the occurrence of subclinical PE and brain natriuretic peptide (BNP) levels among nonacclimatized individuals during an expedition on Mount Elbrus (5642 m).. Seven subjects underwent assessment of vital signs, Lake Louise Score, ultrasound lung comets using handheld echography and circulating BNP using capillary testing at different stages of ascension, in addition to baseline echocardiography. Friedman tests were used to compare serial measurements.. Heart rate, Lake Louise Score (P < 0.0001) and blood pressure (P = 0.037) increased during ascension; oxygen saturation decreased (P < 0.0001). BNP increased (40.7 ± 16.8 vs 19.7 ± 3.04 pg/mL; P < 0.01) after the summit, as did ultrasound lung comet count throughout ascension (P < 0.0001), but both parameters were not correlated (r = 0.36; P = 0.42). Post-summit peak BNP correlated with baseline left ventricular mass index (r = -0.79; P = 0.033).. This study confirms the high incidence of subclinical PE during subacute exposure to hypobaric hypoxia and enhancement of this phenomenon after exertion. Although not correlated with the degree of PE, BNP levels increased after sustained effort at HA, but not at rest. Further investigation is needed to determine the mechanisms underlying the BNP response at HA and its usefulness as a monitoring tool during expeditions.

Topics: Adult; Aged; Altitude; Altitude Sickness; Echocardiography; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Quebec; Reference Values; Retrospective Studies

Topics: Biomarkers; Female; Heart Failure; Heart Failure, Diastolic; HIV Infections; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Cell Surface

This study sought to determine whether biomarkers ST2, growth differentiation factor (GDF)-15, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin I are elevated in patients infected with human immunodeficiency virus (HIV) and are associated with cardiovascular dysfunction and all-cause mortality.. HIV-infected patients have high rates of cardiovascular disease. Markers of myocardial stress may identify at-risk patients and provide additional prognostic information.. Biomarkers and echocardiograms were assessed in 332 HIV-infected patients and 50 age- and sex-matched control subjects. Left ventricular systolic dysfunction was defined as ejection fraction <50%, diastolic dysfunction (DD) as stage 1 or higher, and pulmonary hypertension as pulmonary artery systolic pressure ≥35 mm Hg. Mortality data were obtained from the National Death Index.. Patients with HIV had a median age of 49 years, and 80% were male. Compared with control subjects, HIV-infected patients had higher adjusted percent estimates of all biomarkers except ST2 and interleukin-6. Among HIV-infected patients, 45% had DD; only ST2 was associated with DD (relative risk [RR]: 1.36; p = 0.047). Left ventricular systolic dysfunction was rare in this cohort (5%). Pulmonary hypertension was present in 27% of HIV-infected patients and was associated with GDF-15 (RR: 1.18; p = 0.04), NT-proBNP (RR: 1.18; p = 0.007), and cystatin C (RR: 1.54; p = 0.03). Thirty-eight deaths occurred among HIV-infected patients over a median of 6.1 years. In adjusted analysis, all-cause mortality was independently predicted by ST2 (hazard ratio [HR]: 2.04; p = 0.010), GDF-15 (HR: 1.42; p = 0.0054), high-sensitivity C-reactive protein (HR: 1.25; p = 0.023), and D-dimer (HR: 1.49; p = 0.029). Relationships were unchanged when analyses were restricted to virally suppressed HIV-infected patients receiving antiretroviral therapy.. Among HIV-infected patients, ST2 and GDF-15 were associated with both cardiovascular dysfunction and all-cause mortality, and these variables may be useful at identifying those at risk for developing cardiovascular events and death.

Topics: Adult; Biomarkers; Cohort Studies; Echocardiography; Female; Heart Failure; Heart Failure, Diastolic; HIV Infections; Humans; Hypertension, Pulmonary; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Peptide Fragments; Predictive Value of Tests; Receptors, Cell Surface; Reference Values; Survival Rate

While N-terminal B-type natriuretic peptide (NT-proBNP) has been examined extensively in pulmonary hypertension (PH), limited data exists on the subtype A, C and D. The aim of this prospective pilot study was a head-to-head comparison of NPs in respect to haemodynamic parameters and the influence of renal function.. Plasma samples were drawn during routine right heart catheterization in 62 patients with precapillary PH and 20 control patients. MR-proANP measurements were performed on the automated Kryptor platform, NT-proBNP by CLIA, NT-proCNP and DNP levels by ELISA. Results are expressed as median [range] and tested non-parametrically. Non-parametric locally linear multiple regression was performed to determine the influence of renal function on NP levels. P-values <0.05 were considered significant.. Patients with PH had significantly higher MR-proANP and NT-proBNP levels. NT-proCNP showed a trend to higher levels, while DNP did not differ from control subjects. Both MR-proANP and NT-proBNP were associated with cardiac index (CI), right atrial pressure (RAP), mean pulmonary artery pressure (PAPm) and pulmonary vascular resistance index (PVRI). NT-proCNP was associated with RAP, while DNP showed no associations with haemodynamic variables. Associations of haemodynamic parameters with NPs were weakened in patients with in elevated serum creatinine and showed increased regression slopes.. MR-proANP demonstrated equivalent associations with haemodynamics compared to NT-proBNP, but both markers depend on intact renal function. NT-proCNP was correlated with RAP and renal function, while DNP showed no associations. Larger studies should evaluate MR-proANP as candidate prognostic biomarker in PH.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Case-Control Studies; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Natriuretic Peptides; Peptide Fragments; Predictive Value of Tests; Prospective Studies

Right ventricular diastolic dysfunction (RVDD) is an important prognostic indicator in pulmonary arterial hypertension (PAH). RV vortex rings have been observed in healthy subjects, but their significance in RVDD is unknown. Vorticity, the local spinning motion of an element of fluid, may be a sensitive measure of RV vortex dynamics. Using four-dimensional (4D) flow cardiac magnetic resonance imaging (CMR), we investigated the relationship between right heart vorticity with echocardiographic indexes of RVDD. Thirteen (13) PAH subjects and 10 controls underwent same-day 4D flow CMR and echocardiography. RV diastolic function was assessed using trans-tricuspid valve (TV) early (E) and late (A) velocities, E/A ratio, and e' and a' tissue Doppler velocities. RV and right atrial (RA) integrated mean vorticity was calculated for E and A-wave filling periods using 4D datasets. Compared with controls, A-wave vorticity was significantly increased in RVDD subjects in both the RV [2343 (1,559-3,295) vs. 492 (267-2,649) 1/s, P = 0.028] and RA [30 (27-44) vs. 9 (5-27) 1/s, P = 0.005]. RA E vorticity was significantly decreased [13 (7-22) vs. 28 (15-31) 1/s, P = 0.038] in RVDD. E-wave vorticity correlated TV e', E-,and TV E/A (P < 0.05), and A-wave vorticity associated with both TV A and E/A (P < 0.02). RVDD is associated with alterations in E- and A-wave vorticity, and vorticity correlates with multiple echocardiographic markers of RVDD. Vorticity may be a robust noninvasive research tool for the investigation of RV fluid and tissue mechanical interactions in PAH.

Topics: Aged; Case-Control Studies; Diastole; Echocardiography; Echocardiography, Doppler; Female; Heart Ventricles; Hemodynamics; Humans; Hydrodynamics; Hypertension, Pulmonary; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Ventricular Dysfunction, Right

Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) is a rare disease characterized by a very dismal response to therapy and poor survival. We assessed the effects of up-front combination PAH therapy in patients with SSc-PAH.. In this prospective, multicenter, open-label trial, 24 treatment-naive patients with SSc-PAH received ambrisentan 10 mg and tadalafil 40 mg daily for 36 weeks. Functional, hemodynamic, and imaging (cardiac magnetic resonance imaging and echocardiography) assessments at baseline and 36 weeks included changes in right ventricular (RV) mass and pulmonary vascular resistance as co-primary endpoints and stroke volume/pulmonary pulse pressure ratio, tricuspid annular plane systolic excursion, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide as secondary endpoints.. At 36 weeks, we found that treatment had resulted in significant reductions in median (interquartile range [IQR]) RV mass (28.0 g [IQR, 20.6-32.9] vs. 32.5 g [IQR, 23.2-41.4]; P < 0.05) and median pulmonary vascular resistance (3.1 Wood units [IQR, 2.0-5.7] vs. 6.9 Wood units [IQR, 4.0-12.9]; P < 0.0001) and in improvements in median stroke volume/pulmonary pulse pressure ratio (2.6 ml/mm Hg [IQR, 1.8-3.5] vs. 1.4 ml/mm Hg [IQR 8.9-2.4]; P < 0.0001) and mean ( ± SD) tricuspid annular plane systolic excursion (2.2 ± 0.12 cm vs. 1.65 ± 0.11 cm; P < 0.0001), 6-minute walk distance (395 ± 99 m vs. 343 ± 131 m; P = 0.001), and serum N-terminal pro-brain natriuretic peptide (647 ± 1,127 pg/ml vs. 1,578 ± 2,647 pg/ml; P < 0.05).. Up-front combination therapy with ambrisentan and tadalafil significantly improved hemodynamics, RV structure and function, and functional status in treatment-naive patients with SSc-PAH and may represent a very effective therapy for this patient population. In addition, we identified novel hemodynamic and imaging biomarkers that could have potential value in future clinical trials. Clinical trial registered with www.clinicaltrials.gov (NCT01042158).

Topics: Drug Therapy, Combination; Female; Heart Ventricles; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Phenylpropionates; Phosphodiesterase 5 Inhibitors; Prospective Studies; Pyridazines; Scleroderma, Systemic; Stroke Volume; Tadalafil; Ultrasonography; Vascular Resistance

Besides the established biomarker NT-proBNP, the new cardiovascular biomarkers MR-proANP, MR-proADM, Copeptin, and CT-proET-1 are promising to evaluate hemodynamics, exercise parameters, and prognosis in patients with pulmonary hypertension (PH).. 125 consecutive patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) were prospectively enrolled at five German PH centers. Blood samples were taken during right heart catheterization. The primary study endpoint was the correlation between biomarkers and hemodynamic and exercise parameters. As secondary endpoint, prediction of 1-year mortality was evaluated.. MR-proADM showed the strongest correlations with 6MWD and VO2peak, whereas NT-proBNP showed the strongest correlations with PVR, PAPm, and CI. In multivariate analysis, only MR-proADM was independently associated with exercise variables, whereas only NT-proBNP independently predicted hemodynamic parameters. All biomarkers were associated with 1-year survival, with MR-proADM showing the highest C index of 0.78. In multivariate analysis, MR-proADM predicted survival independent of age, 6-MWD, CI, RAP, and NT-proBNP. The cut-off of 1.08 nmol/l provided a sensitivity of 83 % and specificity of 66 %.. Different biomarkers reflect distinctive disease aspects in PH. NT-proBNP best predicts hemodynamic impairment while MR-proADM strongly correlates with exercise capacity. Additionally, MR-proADM represents a promising new marker to evaluate prognosis in patients with PAH and CTEPH. Multi-marker strategies should further be evaluated.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Pressure; Chronic Disease; Endothelin-1; Exercise Tolerance; Female; Germany; Glycopeptides; Heart Atria; Humans; Hypertension, Pulmonary; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Pulmonary Embolism; Pulmonary Wedge Pressure; Vascular Resistance

Osteoprotegerin (OPG) may predict progression of chronic congestive heart failure (CHF) with increased mortality and play an important role in the development of pulmonary arterial hypertension (PAH). Mounting evidence suggests that PAH developed during CHF is not solely caused by a "passive" increase from the left ventricular enddiastolic pressure, but rather a "reactive" response from contributing lung endothelial dysfunction and vascular remodelling, a pathological process that can be significantly influenced by endothelial progenitor cells (EPCs).This study aims to examine whether circulating EPCs from patients with CHF are affected and if OPG could be implicated during disease progression.. In this study EPCs were isolated, cultured, and quantified from patients of CHF with (n = 20) or without PAH (n=40) as measured by right heart catheterization. Serum levels of OPG and N-terminal pro-brain natriuretic peptide (NT-pro BNP) were analysed and correlated with EPCs.. A significant decrease in circulating EPCs (39.3 ?9.1 vs 67.1 ?10.5 EPCs/x200 field; P <0.05) was found in CHF patients who developed PAH compared to those without PAH. Both OPG (551.90 +/- 49.83 vs. 312.29 +/- 31.12 pg/ml; P<0.05) and NT-pro BNP (2,946.50 +/- 1,434.50 vs. 1,328.20 +/- 811.90; P < 0.05) were also significantly elevated in CHF patients with PA H. Circulating level of OPG correlated inversely with EPCs (r = -0.45, P = 0.037) but positively with mPAP (r =0.53, P=0.011).. Our study demonstrates that OPG elevation and EPC depletion are associated with CHF patients who have developed PAH. The inverse relationship of circulating OPG with EPCs suggests a possible mechanism for OPG in the development of pulmonary vascular dysfunction, thus worsening prognosis for CHF patients.

Topics: Adult; Cells, Cultured; Disease Progression; Echocardiography, Doppler, Color; Endothelial Progenitor Cells; Endothelium, Vascular; Female; Heart Failure, Systolic; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Osteoprotegerin; Peptide Fragments; Prognosis

Cardiovascular involvement is recognized as a poor prognostic factor in systemic sclerosis (SSc). The aim of this study was to evaluate the usefulness of nailfold video-capillaroscopy (NVC), brain natriuretic peptide (BNP) blood level and exercise echocardiography to predict the occurrence of cardiovascular events in SSc.. We prospectively enrolled 65 patients with SSc (age 54±14 years, 30% female) followed in CHU Sart-Tilman, Liège, Belgium. All patients underwent graded semi-supine exercise echocardiography. Both baseline resting pulmonary hypertension (PH) and PH during follow-up (FUPH) were defined as systolic pulmonary arterial pressure (sPAP)>35 mmHg, and exercise-induced PH (EIPH) as sPAP>50 mmHg during exercise.. EIPH was present in 21 patients. During FU (27±18 months), 13 patients developed FUPH and 9 presented cardiovascular complications. Patients with cardiovascular events were significantly older (63±14 vs 52±13 years; P=0.03), presented more frequently NVC grade>2 (89 vs 43%; P=0.009), had higher resting and exercise sPAP (30±6 vs 24±6; P=0.007 and 57±13 vs 44±13 vs mmHg; P=0.01, respectively), and higher BNP blood level (112±106 vs 26±19 pg/ml; P=0.0001). After adjustment for age and gender, NVC grade>2 (ß=2.4±1.1; P=0.03), EIPH (ß=2.30±1.13; P=0.04), FUPH (ß=0.24±0.09; P=0.01 and ß=3.52±1.16; P=0.002, respectively;) and BNP (ß=0.08±0.04; P=0.02) were independent predictors of CV events. Beyond age, an incremental value of EIPH, BNP and NVC grade>2 was predictive of cardiovascular events (P<0.001).. Cardiovascular complications are not rare in SSc (18%). NVC, BNP blood level assessment and exercise echocardiography could be useful tools to identify patients at risk of SSc.

Topics: Adult; Aged; Arterial Pressure; Belgium; Biomarkers; Cardiovascular Diseases; Echocardiography, Stress; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Microcirculation; Microscopic Angioscopy; Middle Aged; Nails; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Prospective Studies; Pulmonary Artery; Risk Assessment; Risk Factors; Scleroderma, Systemic

To evaluate the association between echocardiographic right ventricular (RV) structural and functional parameters and galectin-3 levels in patients with chronic obstructive pulmonary disease (COPD) and associated pulmonary hypertension presenting with acutely aggravated dyspnoea.. We conducted a prospective study on forty patients with COPD and forty healthy volunteers matched for age and sex (mean age 59+/-6 years), measuring galectin-3 and NT-proBNP serum levels and specific echocardiographic parameters.. Galectin-3 was significantly higher in patients with COPD and elevated systolic pulmonary artery pressure than in healthy volunteers and discriminated better between patients with likely and possible pulmonary hypertension when compared to NT-proBNP. In multivariate analysis, the global model was better related to galectin-3 than to NT-proBNP levels (R²=0.61 vs. 0.31, p<0.001). Moreover, in contrast to NT-proBNP levels, correlations between galectin-3 levels and RV dysfunction, as assessed by the E/E' ratio and RV ejection fraction, persisted after adjustment for cardiovascular risk factors and COPD-induced inflammation.. In patients with COPD-associated pulmonary hypertension presenting with acutely aggravated dyspnoea, galectin-3 levels are predictive of RV dysfunction and correlate better with RV dysfunction parameters compared to NT-proBNP.

Topics: Biomarkers; Blood Proteins; Female; Galectin 3; Galectins; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Disease, Chronic Obstructive; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic; Stroke Volume; Ventricular Dysfunction, Right

To investigate the efficacy and safety of inhaled iloprost on top of other pulmonary hypertension (PH) specific therapies for patients with PH and severe right heart failure.. We consecutively enrolled WHO functional class IV patients with PH and chronic thromboembolic pulmonary hypertension (CTEPH) in Shanghai Pulmonary Hospital from January 2011 to January 2013. Inhaled iloprost was administrated to all enrolled patients, oral endothelin antagonist receptors (ERAs) and/or type 5 phosphodiasterase inhibitors (PDE5-I) were also used as basis therapies. The in-hospital outcomes and the changes of right heart functional parameters were observed.. Twenty-four patients with PH and 5 patients with CTEPH were enrolled. After a mean treatment duration of (23 ± 13) days, 3 patients dead and significant improvement was observed in the remaining 26 patients. Compared with the baseline, heart rate decreased from (99 ± 14) to (91 ± 12) bpm (P = 0.001), plasma NT-proBNP level decreased from 5 823 (3 029-13 248) to 3 220 (1 678-6 720) ng/L (P < 0.001), tricuspid annular plane systolic excursion (TAPSE) increased from (1.3 ± 0.4) to (1.4 ± 0.3) cm (P = 0.018), right ventricular diameter decreased (left-to-right diameter from (57 ± 11) to (53 ± 10) mm, P = 0.040, and superoinferior diameter from (69 ± 11) to (64 ± 16) mm, P = 0.027), Tbil also decreased from (41 ± 34) to (26 ± 17) µmol/L (P < 0.001). No severe side effects were observed.. The strategy of inhaled iloprost on top of other PAH-specific target therapy medications is effective and safe for PH patients with severe right heart failure.

Topics: Heart Failure; Humans; Hypertension, Pulmonary; Iloprost; Natriuretic Peptide, Brain; Peptide Fragments; Vasodilator Agents; Ventricular Dysfunction, Right

To evaluate and explore the relationship among the pulmonary artery pressure, Brain natriuretic peptide and the prognosis in the patients with septic shock.. From May 2013 to Oct. 2014, 48 patients were treated with Swan-Ganz catheter to monitor the pulmonary artery pressure, the pulmonary vascular resistance, the pulmonary capillary wedge pressure and cardiac output. Testing brain natriuretic peptide, Analysising the differences between survival patients (27 cases) and dead patients (21 cases) in the PAP, PVR, PCWP, CO and BNP, Analysising the correlation between BNP and PAP, PVR, PCWP, CO by Linear correlation analysis.. It is no difference in hemodynamic parameters between dead patients and survival patients when they come in the hospital (P > 0.05); it is significant difference in hemodynamic parameters between dead patients and survival patients when they came in the hospital after 48 hours or 72 hours [(20.8 ± 5.8) mmHg vs (34.2 ± 7.4) mmHg, P < 0.05], it is no difference in PVR, PCWR and CO at 24 hours, 48 hours or 72 hours. Then it is significant difference in BNP between dead patients and survival patients that they had been entered the hospital after 48 hours or 72 hours [(286.5 ± 75.5) pg/ml vs (675.4 ± 51.3) pg/ml, P < 0.05], it has no obvious correlation among the BNP, PAP and CO.. It prompts a poor prognosis if the patients with septic shock had increased the pulmonary artery pressure and the BNP. Therefore it is need focus on pulmonary hypertension, it is different if BNP of plasma in heart failure patients increased, it does not mean heart function failuring, so it can not be used to give a guide to therapy on heart function.

Topics: Cardiac Output; Heart Failure; Hemodynamics; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Prognosis; Pulmonary Artery; Pulmonary Wedge Pressure; Shock, Septic; Vascular Resistance

To assess the exercise capacity of three kinds of pulmonary artery hypertension using cardiopulmonary exercise testing (CPET).. In the Center for Pulmonary Vascular Disease Diagnosis and Treatment of Fuwai Hospital, idiopathic pulmonary artery hypertension (IPAH), congenital heart disease associated pulmonary artery hypertension (CHD-PAH), connective tissue disease associated pulmonary artery hypertension (CTD-PAH) were enrolled into this study from December 2012 to May 2013. CPET was performed in all patients, and clinical features, routine tests results, N-terminal B-type natriuretic peptide (NT-proBNP), Six-minutes-walk distance (6MWD) were all collected.. Thirty-two patients with IPAH, 38 patients with CHD-PAH, 25 patients with CTD-PAH were enrolled. For IPAH, CHD-PAH, and CTD-PAH patients, the peak oxygen uptake via body weight (VO₂max/kg) was (12.3 ± 2.3), (14.9 ± 4.0), and (11.1 ± 2.5) ml·min⁻¹·kg⁻¹, respectively. The peak VO₂/kg was significantly different within these three groups (P<0.001), and was significantly higher in CHD-PAH patients compared with the other two groups (P=0.003, P<0.001). The peak VO2/heart rate (HR) was (5.8±1.4), (6.4 ± 1.8), (5.3 ± 1.7) ml·beat(-1)·min⁻¹ in the above three groups and was significantly different within these three groups (P=0.034). The peak VO₂/HR was significantly increased in CHD-PAH patients than CTD-PAD patients (P=0.012). The peak HR was (136.1 ± 21.4), (140.8 ± 19.9), (124.5 ± 21.6) beat/min respectively and was significantly lower in CTD-PAD patients than CHD-PAH patients (P=0.009). The 6MWD was significantly decreased in CTD-PAD patients compared with CHD-PAH and IPAH patients (P=0.006, 0.010). Nt-proBNP was significantly decreased in CTD-PAD patients compared with CHD-PAH patients (P=0.012). In Pearson and partial correlation analysis, the peak VO₂/kg was significantly correlated with peak VO₂/HR, peak HR, 6MWD, Nt-proBNP, left ventricular end-diastolic diameter, right ventricular end-diastolic diameter (r=0.477, 0.518, 0.387, 0.465, -0.350, 0.349, -0.259).. CPET parameters can objectively evaluate exercise capacity and cardiopulmonary function of the patients with pulmonary hypertension.

Topics: Connective Tissue Diseases; Exercise Test; Familial Primary Pulmonary Hypertension; Heart Defects, Congenital; Heart Rate; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery

We sought to evaluate the potential utility of echocardiography-derived morphological and functional right ventricular (RV) variables for assessing disease severity of pulmonary arterial hypertension (PAH) and determining the changes in the patient's hemodynamics in the clinical course.. This study consisted of 24 normal controls (the control group) and 24 patients with PAH at rest or with exercise (the PAH group) who underwent echocardiography, right heart catheterization, plasma brain natriuretic peptide (BNP) measurement, and six-minute walk distance (6MWD) test. The PAH group had poorer RV echocardiographic variables than the control group. RV Tei-index was more strongly correlated with 6MWD, BNP, cardiac index, mean pulmonary arterial pressure, and pulmonary vascular resistance (PVR) than other RV echocardiography-derived variables including RV end-diastolic areas, RV fractional area change, and tricuspid annular plane systolic excursion. In 16 of the 24 patients who successfully underwent repeated examination during follow up (13.3 ± 4.9 months; range, 5-24 months), PVR decreased from 486 ± 380 dynes cm(-5) to 346 ± 252 dynes cm(-5), and RV Tei-index decreased from 0.55 ± 0.30 to 0.42 ± 0.17, and the changes in RV Tei-index were correlated with the concomitant changes in PVR during the clinical course of PAH (r=0.706, p=0.002). Tricuspid annular plane systolic excursion and RV fractional area change did not change during the follow up.. Quantitative echocardiography revealed that the measurement of RV Tei-index is of great clinical utility for predicting disease severity of PAH and determining the changes in the patient's hemodynamics in the clinical course.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Cardiac Catheterization; Echocardiography; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Heart Ventricles; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Artery; Severity of Illness Index; Vascular Resistance; Walking; Young Adult

To evaluate the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels along with spontaneous breathing trial (SBT) in the prediction of ventilator weaning outcome among respiratory distress syndrome (RDS) preterm infants ready to wean.. NT-proBNP along with plasma albumin concentration, serum sodium, serum potassium, and hematocrit were measured immediately before SBT in preterm infants (≤32 weeks) mechanically ventilated due to RDS. Extubation was considered successful if infants remained extubated >48 hr. Either SBT failure or extubation failure was considered weaning failure.. Sixty-three of 88 infants passed the SBT and were subsequently extubated. Of these, two (3.2%) cases rapidly developed laryngeal dyspnea imposing reintubation (excluded from analysis). Of the remaining 61 infants, 45 (73.8%) cases had successful extubation, and 16 (26.2%) cases were reintubated. Infants who failed weaning had lower gestational age, birth weight, and plasma albumin concentrations, higher NT-proBNP, doses of surfactant, occurrence of ventilator-associated pneumonia, and occurrence of pulmonary arterial hypertension than those who did not. NT-proBNP was the only independent factor that could predict weaning failure (OR = 1.872; P = 0.044). The ROC-AUC for NT-proBNP to predict weaning failure was 0.977 (95% CI 0.918-0.997; P < 0.001). The cut-off of NT-proBNP level 18,500 pg/ml to predict weaning failure had a positive likelihood ratio of 25.180. The addition of NT-proBNP to SBT in prediction of weaning failure significantly improved the net reclassification improvement (NRI = 0.224; P = 0.034).. NT-proBNP is an independent factor that could predict weaning failure. Measurement of NT-proBNP prior to SBT may be helpful in promoting successful ventilator weaning along with SBT.

Topics: Female; Hematocrit; Humans; Hypertension, Pulmonary; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pneumonia, Ventilator-Associated; Potassium; Prognosis; Respiratory Distress Syndrome, Newborn; Serum Albumin; Sodium; Ventilator Weaning

Sudden cardiac death (SCD) mostly resulting from ventricular arrhythmia remains a cause of mortality in 19-30% of adults with congenital heart defects. Indications for implantable cardioverter-defibrillators in primary prophylaxis are still under research. MicrovoltT wave alternans (MTWA) is one of the SCD risk stratification methods. We determined the incidence of MTWA in these patients and its coincidence with ventricular arrhythmia, as well as risk factors of ventricular arrhythmia/SCD.. 204 patients with complex congenital heart anomalies and 45 healthy volunteers underwent ambulatory ECG monitoring, a cardiopulmonary test, B-type natriuretic peptide assessment, echocardiography and an MTWA test. After excluding technically inadequate traces, the remaining 179 patients and 43 controls were classified into MTWA positive (+), negative (-) and indeterminate (ind) subgroups. Additionally, MTWA (+) and MTWA (ind) formed an 'abnormal' group, labeled MTWA (non-).. Abnormal MTWA was observed more frequently in the study group compared to controls (59 [33.0%] vs. 1 [2.3%], p = 0.000001). The MTWA (non-) group compared to MTWA (-) presented a higher number of males (61.0% vs. 37.5%, p = 0.005), predominance of patients with NYHA > I (44.1% vs. 25.0%, p = 0.007), pulmonary hypertension (16.9% vs. 0.8%, p = 0.00007), lower blood saturation (97% [73-100] vs. 99% [69-100], p = 0.0003), higher incidence of malignant arrhythmia (9 [15.2%] vs. 3 [2.5%], p = 0.003), lower peak oxygen consumption VO2 [mL/kg/min] (23.1 ± 5.9 vs. 26.3 ± 6.7, p = 0.002), higher VE//VCO2 slope (36.0 [25-74] vs. 31.0 [21-58], p = 0.01). Multivariate logistic regression analysis proved that pulmonary hypertension (OR = 13.7, p = 0.03), male gender (OR = 10.4,p = 0.00002), VE/VCO2 slope (OR = 1.07, p = 0.045) and VO2 (OR = 0.89, p = 0.04) increase the probability of MTWA (non-).. Abnormal MTWA is more frequent in adults with congenital heart diseases than in the healthy population. Its probability increases in patients demonstrating clinical findings conducive to lethal arrhythmia like heart failure and pulmonary hypertension.

Topics: Action Potentials; Adolescent; Adult; Age Factors; Aged; Arrhythmias, Cardiac; Biomarkers; Case-Control Studies; Chi-Square Distribution; Comorbidity; Death, Sudden, Cardiac; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Conduction System; Heart Defects, Congenital; Heart Rate; Humans; Hypertension, Pulmonary; Incidence; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Oxygen Consumption; Poland; Risk Assessment; Risk Factors; Young Adult

Ventricular-arterial coupling is a measure of the relationship between ventricular contractility and afterload. We sought to determine the relationship between ventricular-arterial coupling and right ventricular (RV) remodeling in a novel porcine model of progressive pulmonary hypertension (PH).. Chronic PH was induced in pigs by ligation of the left pulmonary artery (PA) followed by 5 weekly injections of cyanoacrylate to progressively obstruct the right lower lobe arteries (PH group, n = 10). At 6 weeks, 5 PH animals underwent reperfusion of the left lung through conduit anastomosis to decrease RV afterload, whereas 5 other animals received no treatment. Five sham-operated piglets were used as controls. RV function was assessed using echocardiography and conductance catheterization. RV gene expression of beta-myosin heavy chain (β-MHC) and B-type natriuretic peptide (BNP) were quantified by polymerase chain reaction.. At 6 weeks, compared with controls, the PH group had higher mean PA pressure (32 ± 6 vs 14 ± 2 mm Hg, p < 0.01). The increase in RV elastance was insufficient to compensate for the increase in pulmonary arterial elastance in the PH group and altered ventricular-arterial coupling occurred (0.65 ± 0.16 vs 1.28 ± 0.14, p < 0.01). The degree of ventricular-arterial uncoupling was related to RV enlargement and systolic dysfunction. Ventricular-arterial uncoupling and increased RV mass index were associated with up-regulation of β-MHC and BNP expression.. Ventricular-arterial coupling is closely associated with ventricular remodeling and systolic function as well as contractile and BNP gene expression. Dynamic changes in myosin expression may determine RV work efficiency in PH.

Topics: Animals; Biomarkers; Cyanoacrylates; Disease Models, Animal; Hypertension, Pulmonary; Myosin Heavy Chains; Natriuretic Peptide, Brain; Pulmonary Artery; Swine; Ventricular Dysfunction, Right; Ventricular Remodeling

Submaximal exercise testing (SET) assesses functional exercise capacity in pulmonary arterial hypertension (PAH) patients and provides additional physiologic information compared with the 6-min walk test (6MWT). The relative correlations of the 6MWT and SET using SHAPE-HF™ with other markers of PAH severity, particularly echocardiogram (ECHO)-derived mean pulmonary artery pressure (MPAP), have not been investigated.. (i) Examine the correlation between SHAPE measures with the 6-min walk distance (6MWD), and (ii) Compare SHAPE parameters and the 6MWD to clinical measures of PAH severity.. Fifty-five consecutive group 1 PAH outpatients were evaluated in a single pulmonary hypertension referral center from March 2011 to June 2012.. World Health Organization (WHO) functional class (FC), brain natriuretic peptide (BNP), ECHO, 6MWD and SHAPE results. Data are reported using mean ± standard deviation and Spearman correlation coefficients (r).. Nine patients were excluded. Of the 46 remaining patients, 78% were women and the average age was 61 ± 13 years. PAH characteristics: WHO FC III-IV 48%; idiopathic PAH 52%; BNP 198 ± 277 pg/mL; 6MWD 399 ± 97 m; ECHO right atrial pressure (RAP) 7 ± 4, pulmonary artery systolic pressure (PASP) 63 ± 29 and MPAP 45 ± 17 mmHg. SET with SHAPE results: mean partial pressure of end-tidal (PET ) CO2 31 ± 6 mmHg at end-exercise; ventilatory efficiency (VE/VCO2 ) 43 ± 16. Significant correlations were found between the 6MWD and SHAPE variables: VE/VCO2 (r = -0.57, P < 0.0001) and end-exercise PET CO2 (r = 0.42, P = 0.004). VE/VCO2 correlated with WHO FC, BNP, RAP, MPAP and PASP and 6MWD only with WHO FC, BNP and PASP.. SHAPE outperformed 6MWD in comparison with other measures of PAH disease severity.

Topics: Aged; Cohort Studies; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Ventilation; Severity of Illness Index; Time Factors

The detection of elevations in cardiorenal biomarkers, such as troponins, B-type natriuretic peptides (BNPs), and neutrophil gelatinase-associated lipocalins, are associated with poor outcomes in patients hospitalized with acute heart failure. Less is known about the association of these markers with adverse events in chronic right ventricular dysfunction due to pulmonary hypertension, or whether their measurement may improve risk assessment in the outpatient setting.. We performed a cohort study of 108 patients attending the National Pulmonary Hypertension Unit in Dublin, Ireland, from 2007 to 2009. Cox proportional hazards analysis and receiver operating characteristic curves were used to determine predictors of mortality and hospitalization. Death or hospitalization occurred in 50 patients (46.3%) during the median study period of 4.1 years. Independent predictors of mortality were: 1) decreasing 6-minute walk test (6MWT; hazard ratio [HR] 12.8; P < .001); 2) BNP (HR 6.68; P < .001); and 3) highly sensitive troponin (hsTnT; HR 5.48; P < .001). Adjusted hazard analyses remained significant when hsTnT was added to a model with BNP and 6MWT (HR 9.26, 95% CI 3.61-23.79), as did the predictive ability of the model for death and rehospitalization (area under the receiver operating characteristic curve 0.81, 95% CI 0.73-0.90).. Detection of troponin using a highly sensitive assay identifies a pulmonary hypertension subgroup with a poorer prognosis. hsTnT may also be used in a risk prediction model to identify patients at higher risk who may require escalation of targeted pulmonary vasodilator therapies and closer clinical surveillance.

Topics: Acute-Phase Proteins; Adult; Aged; Biomarkers; Chronic Disease; Cohort Studies; Exercise Test; Female; Hospitalization; Humans; Hypertension, Pulmonary; Ireland; Lipocalin-2; Lipocalins; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Outpatients; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Proto-Oncogene Proteins; Risk Assessment; ROC Curve; Troponin T; Ventricular Dysfunction, Right

Recent clinical trials in pulmonary arterial hypertension have included World Health Organization functional classes I and II patients. However, the impact of baseline functional class and other measures of severity on outcomes has not been evaluated in detail.. Outcomes at 12 weeks for patients grouped by functional class, haemodynamics, brain natriuretic peptide (BNP) level and 6-min walk distance (6MWD) were evaluated for patients in the Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter Efficacy Study 1 and 2 (ARIES)-1 and 2 pivotal trials of ambrisentan, a once-daily oral endothelin-1 antagonist. Long-term outcomes in the ARIES-E extension study were also evaluated.. At 12 weeks, ambrisentan-treated patients with both early and late functional class showed similar improvement in 6MWD relative to placebo. However, patients with more severe disease tended to have greater improvement in 6MWD after grouping by other measures of severity. This included higher baseline BNP level, shorter baseline 6MWD and more severe baseline haemodynamics (p < 0.05 for BNP and p = NS for other comparisons, analysed as interaction terms). During long-term open label follow-up, maintenance of 6MWD improvement, freedom from clinical worsening and survival were also numerically worse for patients who were functional class III/IV at baseline.. Patients with both less severe and more severe PAH benefited from ambrisentan therapy vs. placebo in 12-week clinical trials and during long-term follow up, but greater improvement vs. placebo was seen for those with higher BNP levels.

Topics: Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Phenylpropionates; Pyridazines; Randomized Controlled Trials as Topic; Research Design; Severity of Illness Index; Survival Analysis; Treatment Outcome

B-type natriuretic peptide (BNP) is a strong predictor of mortality in adult patients with various forms of pulmonary hypertension (PH) and may be a strong prognostic marker in extremely low birth weight (ELBW) infants with bronchopulmonary dysplasia (BPD) associated PH as well. We sought to assess the relationship between BNP levels and all-cause mortality in a cohort of ELBW infants with BPD and PH.. We retrospectively identified ELBW infants with BPD and PH who had serum BNP levels measured as part of routine clinical care in the neonatal intensive care unit. Peak serum BNP levels were correlated with survival to discharge or death.. Thirty-six ELBW infants (mean gestational age 26.0 ± 1.9 weeks and mean birth weight 740 ± 290 grams) with BPD and PH had available survival data and had serum BNP levels measured. Peak BNP level was significantly lower among infants who survived than among those who died (128 pg/ml, [IQR 23 to 463] vs. 997 pg/ml, [IQR 278 to 1770], P < 0.004). On multivariate Cox proportional hazard analysis, BNP predicted survival independent of age, gender, and BPD severity. Area under receiver operator characteristic analysis identified a BNP value of 220 pg/ml to have 90% sensitivity and 65% specificity in predicting mortality.. BNP estimation may be useful as a prognostic marker of all-cause mortality in ELBW infants with BPD associated PH.

Topics: Bronchopulmonary Dysplasia; Cohort Studies; Female; Humans; Hypertension, Pulmonary; Infant, Extremely Low Birth Weight; Infant, Newborn; Male; Natriuretic Peptide, Brain; Retrospective Studies

Cystatin C (CysC), a novel marker of renal function, predicts left heart failure and cardiovascular mortality. The hypothesis that serum CysC levels correlate with right ventricular (RV) morphology, function and pressure in pulmonary arterial hypertension (PAH) was tested.. As part of a prospective study, 14 PAH subjects and 10 matched controls underwent same-day echocardiography, cardiac magnetic resonance imaging (CMR), and phlebotomy for CysC, brain natriuretic peptide (BNP), and N-terminal BNP (NT-ProBNP). RV ejection fraction (RVEF), end-diastolic volume, end-systolic volume and mass were calculated using CMR. RV systolic pressure (RVSP), strain and diastolic function (including tricuspid valve (TV) E velocity, A velocity, e' velocity, E/A ratio and E/e' ratio) were assessed using echocardiography.. RVSP was significantly elevated in PAH subjects versus controls (57 ± 17 vs. 28 ± 8 mm Hg, P < 0.0001). CysC was abnormally elevated in the PAH cohort when compared with controls (1.00 ± 0.23 vs 0.78 ± 0.05 mg/L, P = 0.001). CysC positively correlated with RVSP (rho 0.61, P = 0.002), RV end-diastolic volume (rho 0.50, P = 0.01), RV end-systolic volume (rho 0.58, P = 0.003), mass index (rho 0.66, P = 0.0004), strain (rho 0.51, P = 0.01) and strain rate (rho 0.51, P = 0.01) and negatively correlated with RVEF (rho -0.58, P = 0.003) and TV e' (rho -0.75, P < 0.0001). The same correlations with BNP and NT-ProBNP were comparable with CysC.. In a small cohort, CysC accurately correlates with RV pressure, function and morphology. CysC may represent a novel PAH biomarker.

Topics: Biomarkers; Cystatin C; Female; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Pulmonary Circulation; Reproducibility of Results; Statistics as Topic; Stroke Volume; Ventricular Function, Right

Interstitial lung diseases (ILD) are often associated with pulmonary hypertension (PH). This study aimed to evaluate the therapeutic benefit of phosphodiesterase-5 (PDE-5) inhibitors in pulmonary hypertension secondary to ILD.. Patients with ILD and PH were treated with sildenafil or tadalafil. Right heart catheterization was performed before and after a minimum of 3-month treatment. In addition, lung function, 6-min walk distance (6MWD) and plasma brain natriuretic peptide (BNP) concentration were assessed.. Ten ILD patients (three female, mean age 64.4 ± 9.0 years, six with idiopathic pulmonary fibrosis (IPF), four with hypersensitivity pneumonitis, (HP)) with significant precapillary PH (mean pulmonary artery pressure (PAPm) ≥ 25 mmHg, pulmonary vascular resistance (PVR) > 280 dyn*s*cm(-5) ; pulmonary artery wedge pressure (PAWPm) ≤ 15 mmHg) were treated with either sildenafil (n = 5) or tadalafil (n = 5). Pulmonary haemodynamics were severely impaired at baseline (PAPm 42.9 ± 5.4 mmHg; cardiac index (CI) 2.7 ± 0.6 L/min/m2; PVR 519 ± 131 dyn × sec × cm(-5)). After mean follow-up of 6.9 ± 5.8 months an increase in CI (2.9 ± 0.7 L/min/m2 , P = 0.04) and a decrease in PVR (403 ± 190 dyn × sec × cm(-5) , P = 0.03) were observed. 6MWD and BNP did not change significantly.. Our data suggest that treatment with PDE-5 inhibitors improves pulmonary haemodynamic patients with PH secondary to ILD.

Topics: Aged; Aged, 80 and over; Carbolines; Female; Follow-Up Studies; Hemodynamics; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Phosphodiesterase 5 Inhibitors; Pilot Projects; Piperazines; Purines; Respiratory Function Tests; Sildenafil Citrate; Sulfonamides; Tadalafil; Walking

Pulmonary endarterectomy (PEA) is established for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). Recently, percutaneous transluminal pulmonary angioplasty (PTPA) has been added for peripheral-type CTEPH, whose lesions exist in segmental, subsegmental, and more distal pulmonary arteries. A shift in clinical practice of interventional therapies occurred in 2009 (first mainly PEA, later PTPA). We examined the latest clinical outcomes of patients with CTEPH.. This study retrospectively included 136 patients with CTEPH. Twenty-nine were treated only with drug (Drug-group), and the other 107 underwent interventional therapies (Interventions-group) (39 underwent PEA [PEA-group] and 68 underwent PTPA [PTPA-group]). Total 213 PTPA sessions (failures, 0%; mortality rate, 1.47%) was performed in the PTPA-group (complications: reperfusion pulmonary edema, 7.0%; hemosputum or hemoptysis, 5.6%; vessel dissection, 2.3%; wiring perforation, 0.9%). Although baseline hemodynamic parameters were significantly more severe in the Interventions-group, the outcome after the diagnosis was much better in the Interventions-group than in the Drug-group (98% vs. 64% 5-year survival, p<0.0001). Hemodynamic improvement in the PEA-group was a 46% decrease in mean pulmonary arterial pressure (PAP) and a 49% decrease in total pulmonary resistance (TPR) (follow-up period; 74.7 ± 32.3 months), while those in the PTPA-group were a 40% decrease in mean PAP and a 49% decrease in TPR (follow-up period; 17.4 ± 9.3 months). The 2-year survival rate in the Drug-group was 82.0%, and the 2-year survival rate, occurrence of right heart failure, and re-vascularization rate in the PEA-group were 97.4%, 2.6%, and 2.8%, and those in the PTPA-group were 98.5%, 2.9%, and 2.9%, respectively.. The patients who underwent interventional therapies had better results than those treated only with drugs. The availability of both of these operative and catheter-based interventional therapies leads us to expect the dawn of a new era of therapeutic strategies for CTEPH.

Topics: Angioplasty; Chronic Disease; Endarterectomy; Endpoint Determination; Exercise; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Practice Patterns, Physicians'; Pulmonary Embolism; Treatment Outcome

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a routinely used prognostic parameter in patients with pre-capillary pulmonary hypertension (PH). As it accumulates in the presence of impaired renal function, the clinical utility of NT-proBNP in PH patients with concomitant renal insufficiency remains unclear. In a retrospective approach, patients with pre-capillary PH (group I or IV) and concomitant renal insufficiency at time of right heart catheterization (glomerular filtration rate (GFR) ≤60 ml/min/1.73 m2) were identified out of all prevalent pre-capillary PH patients treated at a single center. Forty patients with renal insufficiency (25.8%) were identified and matched regarding hemodynamic parameters with a control group of 56 PH patients with normal renal function (GFR >60 ml/min/1.73 m2). Correlations of NT-proBNP levels with hemodynamic and prognostic parameters (time to clinical worsening and overall survival) were assessed. Overall, GFR correlated inversely with NT-proBNP and had the strongest influence on NT-proBNP levels in a stepwise multiple linear regression model including hemodynamic parameters and age (r2 = 0.167). PH patients with renal insufficiency had significant higher levels of NT-proBNP (median: 1935 ng/l vs. 573 ng/l, p = 0.001). Nevertheless, NT-proBNP correlated with invasive hemodynamic parameters in these patients. Using higher cut-off values than in patients with preserved renal function, NT-proBNP levels were significantly associated with time to clinical worsening (>1660 ng/l, p = 0.001) and survival (>2212 ng/l, p = 0.047) in patients with renal insufficiency. Multivariate Cox's proportional hazards analysis including established prognostic parameters, age and GFR confirmed NT-proBNP as an independent risk factor for clinical worsening in PH patients with renal insufficiency (hazard ratio 4.8, p = 0.007). Thus, in a retrospective analysis we showed that NT-proBNP levels correlated with hemodynamic parameters and outcome regardless of renal function. By using higher cut-off values, NT-proBNP seems to represent a valid clinical marker even in PH patients with renal insufficiency.

Topics: Aged; Biomarkers; Capillaries; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Renal Insufficiency; Survival Analysis; Time Factors

Summer heat waves with temperature extremes are becoming more frequent with growing numbers in morbidity and mortality in patients with respiratory diseases. The aim of this study was to evaluate the ramifications of heat stress (temperature >25 °C) on the health status of patients with pulmonary arterial hypertension (PAH).. Fifteen patients with PAH (mean age = 66.7 ± 5.2 years) continuously wore an accelerometer from April 1 to September 30, 2011, and their daily step count was recorded. In addition, patients kept a diary to record data on seven standardized questions regarding their daily symptoms. Echocardiography, 6-minute walk test, NTproBNP, and Modified Medical Research Council Scale (MMRC) were assessed at baseline and at the end of the study after 6 months.. On heat-stress days, patients showed significantly more symptoms and lower total steps/day compared to thermal comfort days (3,995 ± 2,013 steps/day vs. 5,567 ± 2,434 steps/day, respectively; P < 0.001). There was a significant negative correlation between total steps/day and Temp(max) (R = -0.47; P < 0.001) and humidity (R = -0.34; P < 0.001). A significant positive correlation was found between daily symptoms and Temp(max) (R = +0.79; P < 0.001) and humidity (R = +0.23; P < 0.001).. Heat stress is associated with a compromised clinical status in patients with PAH. Adaptation strategies must be implemented to prevent heart-related morbidity, including therapeutic adjustments and adequate room cooling in the patient's home and at the hospital.

Topics: Actigraphy; Activities of Daily Living; Aged; Biomarkers; Exercise Test; Exercise Tolerance; Female; Germany; Health Status; Heat Stress Disorders; Hot Temperature; Humans; Humidity; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Seasons; Time Factors; Urban Health

Inflammatory, endothelial and neurohormonal biomarkers are involved in heart failure (HF) and pulmonary hypertension (PH) pathogenesis.. To study these biomarkers in PH due to advanced HF.. Thirty adults with HF were included. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hsCRP), endothelin-1 and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were measured in peripheral vein and pulmonary artery during right heart catheterisation.. IL-6, TNF-α, hsCRP and NT-proBNP correlated with pulmonary pressures independent of ventricular function, HF etiology and vascular bed. IL-6 was independent predictor of systolic pulmonary artery pressure (sPAP).. Inflammatory biomarkers correlate to PH severity. IL-6 predicts sPAP in advanced HF.

Topics: Aged; Biomarkers; C-Reactive Protein; Endothelin-1; Female; Heart Failure; Hemodynamics; Humans; Hypertension, Pulmonary; Interleukin-6; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Tumor Necrosis Factor-alpha

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with a higher risk of cardiovascular disease (CVD). Previous studies have indicated that the reduction of bone marrow-derived multipotent progenitors (CD34+ cells) may lead to reduced vascular repair capacity and may help to identify patients that pose an increased cardiovascular risk. However, the relationship between CD34+cells and CVD risk in AECOPD remains unclear. The aim of the present study was to assess CD34+ cell counts and their relationship with classical adverse cardiac outcome predictors in AECOPD.. For our study, 27 patients with AECOPD (GOLD stage III, IV), 26 with stable COPD (GOLD stage III, IV), and 24 healthy controls were enrolled. CD34+ cells were enumerated, and plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), a systemic inflammation marker (high-sensitivity C-reactive protein, hsCRP) and mobilisation marker (matrix metalloproteinase-9, MMP-9), were measured. Echocardiography was performed to evaluate cardiac dysfunction and pulmonary hypertension.. Compared with healthy controls, AECOPD patients had a significantly decreased CD34+ cell count (5.1 ± 2.6 versus 9.4 ± 3.6 × 10³/ml), especially in patients with a prior history of acute exacerbation. For patients with AECOPD, the CD34+ cell count was inversely correlated with NT-proBNP levels, pulmonary artery systolic pressure (PASP) and resting heart rate, and positively correlated with left ventricular ejection fraction (LVEF). In all three groups, CD34+ cell count was negatively correlated with hsCRP.. The circulating CD34+ cell count was decreased and correlated with cardiac dysfunction in AECOPD patients, and thus may account for the increased cardiovascular risk in this population.

Topics: Aged; Antigens, CD34; C-Reactive Protein; Case-Control Studies; Cell Count; Disease Progression; Echocardiography; Female; Heart Rate; Humans; Hypertension, Pulmonary; Male; Matrix Metalloproteinase 9; Middle Aged; Multipotent Stem Cells; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Disease, Chronic Obstructive; Stroke Volume; Ventricular Dysfunction, Left

To be able to design goal-oriented treatment strategies in paediatric pulmonary arterial hypertension (PAH), we aimed to identify treatment goals by investigating the prognostic value of treatment-induced changes in noninvasive predictors of transplant-free survival. 66 consecutive, treatment-naïve paediatric PAH patients in the Dutch National Network for Paediatric Pulmonary Hypertension who started taking PAH-targeted drugs between January 2000 and April 2013 underwent prospective, standardised follow-up. Clinical, biochemical and echocardiographic measures were longitudinally collected at treatment initiation and follow-up, and their respective predictive values for transplant-free survival were assessed. Furthermore, the predictive values of treatment-induced changes were assessed. From the identified set of baseline predictors, the variables World Health Organization functional class (WHO-FC), N-terminal pro-brain natriuretic peptide (NT-proBNP) and tricuspid annular plane systolic excursion (TAPSE) were identified as follow-up predictors in which treatment-induced changes were associated with survival. Patients in whom these variables improved after treatment showed better survival (p<0.002). Therefore, WHO-FC, NT-proBNP and TAPSE are not only predictors of transplant-free survival in paediatric PAH but can also be used as treatment goals, as treatment-induced improvements in these variables are associated with improved survival. The identification of these variables allows for the introduction of goal-oriented treatment strategies in paediatric PAH.

Topics: Adolescent; Cardiac Catheterization; Child; Child, Preschool; Cohort Studies; Disease Progression; Echocardiography; Endothelin Receptor Antagonists; Female; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lung Transplantation; Male; Natriuretic Peptide, Brain; Patient Care Planning; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Prospective Studies; Prostaglandins I; Pulmonary Wedge Pressure; Survival Analysis; Tricuspid Valve Insufficiency

We aimed to assess the relationship between right ventricle (RV) dysfunction parameters and the soluble IL-1 receptor family member (sST2) in patients with secondary pulmonary hypertension owing tochronic obstructive pulmonary disease.. A total of 36 patients with chronic obstructive pulmonary disease and secondary pulmonary hypertension (mean age: 59 ± 7 years) and 36 healthy volunteers (mean age: 59 ± 8 years) were enrolled in the study. sST2 and NT-proBNP levels, as well as specific echocardiographic parameters were measured.. Both sST2 and NT-proBNP levels were greater in the test group. The sST2 levels were inversely associated with RV fractional area change(r = -0.762; p < 0.001), as well as with the RV ejection fraction (r = -0.799; p < 0.001), tricuspid annular plane systolic excursion (r = -0.773; p < 0.001) and increased pulmonary artery systolic pressure (r = 0.603;p < 0.001). Receiver operating characteristic curve analysis revealed that sST2 had lower sensitivity for identifying RV dysfunction when compared with NT-proBNP (71.4 vs 100%), despite having the same specificity (84%).. The current study reveals correlations between sST2 levels and echocardiographic parameters of RV dysfunction, suggesting that use of sST2 and NT-proBNP may improve diagnosis and risk stratification in patients with secondary pulmonary hypertension owing to chronic obstructive pulmonary disease.

Topics: Aged; Biomarkers; Female; Humans; Hypertension, Pulmonary; Interleukin-1 Receptor-Like 1 Protein; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Disease, Chronic Obstructive; Receptors, Cell Surface; Ventricular Dysfunction, Right

Pulmonary hypertension (PH), an increasingly recognised complication of pulmonary sarcoidosis, is associated with increased morbidity and mortality Evidence of benefit with targeted therapies in sarcoidosis associated pulmonary hypertension (SAPH) is limited.. We conducted a retrospective review of patients with sarcoidosis and right heart catheter proven PH who received treatment with targeted therapies (phosphodiesterase-5 inhibitors, endothelin receptor antagonists, or combination) at our hospital. Six minute walk test (6MWT), World Health Organisation (WHO) functional class, echocardiography, pulmonary function test (PFT) and serum brain natriuretic peptide (BNP) data were collected at baseline and during follow-up.. Thirty-three patients (16 men) with a mean age of 55.5 ± 10.7 years and mean pulmonary artery pressure of 44.0 ± 8.6 mm Hg received treatment with targeted PH therapies (sildenafil=29, bosentan=4). At six months, median six minute walk distance improved from 227 (88-526) meters to 240 (140-380) metres (p=0.04), median serum BNP levels improved from 35 (2-424) pmol/L to 26 (4-255) pmol/L (p<0.01), and at echocardiography, median tricuspid annular plane systolic excursion (TAPSE) improved from 17.5 (8.0-27.0) mm to 20.0 (15.0-27.0) mm (p=0.03). WHO functional class improved in 14 patients. Two patients developed side-effects attributed to sildenafil (n=1) or bosentan (n=1), requiring conversion to alternative PH therapies. Ten patients died, and one patient underwent lung transplantation, a median of 13.5 (3-37) months after commencing targeted therapies.. Our results suggest that targeted therapies are safe in patients with SAPH. Controlled trials are warranted before therapeutic recommendations can be made.

Topics: Aged; Antihypertensive Agents; Arterial Pressure; Biomarkers; Endothelin Receptor Antagonists; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; London; Lung Transplantation; Male; Middle Aged; Molecular Targeted Therapy; Natriuretic Peptide, Brain; Phosphodiesterase 5 Inhibitors; Recovery of Function; Retrospective Studies; Sarcoidosis, Pulmonary; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Vasodilator Agents

Pulmonary hypertension (PH) causes mortality in systemic sclerosis (SSc). Pulmonary arterial hypertension (PAH) and left heart disease (LHD) are frequent causes of PH. Therefore, we studied PAH and LHD in early PH.. A total of 432 French Canadian SSc patients were studied retrospectively. All underwent screening for PH. We analysed clinical, serological, and radiographic data from 26 patients with early PH diagnosed by right heart catheterization (RHC). SSc patients with (n = 21) and without PH (n = 19) were prospectively re-evaluated by cardiac magnetic resonance imaging (MRI) and serial measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the haemodynamic biomarkers mid-regional pro-atrial natriuritic peptide (MR-proANP) and mid-regional pro-adrenomedullin (MR-proADM).. The most frequent cause of early PH was LHD (58%). PAH was seen in 34% of patients. No association was found between the type of PH and autoantibodies. Early LHD-PH, but not early PAH, was associated with lower NT-proBNP (p = 0.024), but MR-proANP and MR-proADM levels were higher in early LHD-PH than in patients without PH (p = 0.014 and p = 0.012, respectively). Only one patient had abnormal cardiac MRI explaining LHD-PH.. Early PH in SSc, like late PH, is heterogeneous and RHC is essential for determining its underlying cause. The most frequent cause of early PH was LHD. Levels of MR-proANP and MR-proADM, but not NT-proBNP, were increased in early LHD-PH, and may be more reliable than NT-proBNP as a biomarker of early PH in this subgroup of patients. Cardiac MRI did not explain LHD-PH. This study is the first to identify a high frequency of LHD in early PH correlating with normal NT-proBNP levels but increased MR-proANP and MR-proADM levels in SSc patients.

Topics: Adrenomedullin; Adult; Aged; Biomarkers; Canada; Female; Fibrosis; Heart Diseases; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Scleroderma, Systemic

To investigate long-term efficacy and safety of ambrisentan monotherapy in patients with pulmonary arterial hypertension (PAH).. Patients with PAH who received 2.5 mg or 5 mg of ambrisentan once daily between July 10, 2011 and August 30, 2012 for at least 6 months were enrolled. The efficacy endpoints were change in exercise capacity, World Health Organization (WHO) functional class and N-terminal pro-brain natriuretic peptide (NT-proBNP) level, echocardiographic parameters. The safety endpoint was the safety of long-term ambrisentan administration, as defined by the incidence and severity of adverse events.. A total of 18 patients with PAH were enrolled. Mean age was (39 ± 17) years, 8 (55.6%) were female, and 11 (61.1%) patients were in WHO functional class III. The median duration of treatment was 17 months (range: 6-26 months). After treatment, the 6MWD was significantly increased[ (495 ± 97) m vs. (400 ± 91) m, P < 0.001], NT-proBNP was significantly reduced [308 (53-1 645) ng/L vs. 80(22-454) ng/L, P = 0.005], the systolic pulmonary artery was significantly decreased [(62 ± 30) mmHg vs. (82 ± 41) mmHg, P = 0.001] and left ventricular end diastolic diameter was significantly increased [(44 ± 6) mm vs. (40 ± 6) mm, P < 0.004] compared to pre-treatment. WHO functional class was improved compared with baseline in 11(61.1%) patients, stable in 7(38.9%) patients. No patient died during the treatment period. No patient was withdrawn from this study for safety reasons.. Long-term treatment of ambrisentan can effectively improve the exercise capacity, reduce systolic pulmonary artery pressure and NT-proBNP in PAH patients. Ambrisentan is safe and well tolerated in Chinese PAH patients.

Topics: Adult; Blood Pressure; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Phenylpropionates; Pyridazines; Treatment Outcome; Young Adult

We present in this paper results of assessment of functional state of right ventricular (RV) myocardium in 38 patients with acute pulmonary embolism (PE) before and after endovascular recanalization of pulmonary arteries supplemented with thrombolytic therapy. According to echocardiography data RV dysfunction was detected in 60.5% of cases, while an elevated concentration of brain natriuretic peptide (BNP) in blood plasma was observed in all patients. None of the patients had elevated level of troponin I. An increased concentration of BNP in blood plasma with normal troponin level in patients with acute PE was indicative of a hidden RV dysfunction due to its dilatation, acute volume or pressure overload without evidence of myocardial damage. Implications. All patients with acute pulmonary embolism who are hemodynamically stable, but have elevated levels of plasma BNP should undergo thrombolytic therapy (TLT) with the aim of early recanalization of pulmonary arteries and elimination of RV dysfunction. Early thrombolytic recanalization of the pulmonary arteries not only provides restoration of impaired RV function, but also prevents formation of post embolic chronic pulmonary hypertension and improves clinical prognosis.

Topics: Acute Disease; Adult; Aged; Echocardiography; Female; Fibrinolytic Agents; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Pulmonary Embolism; Thrombolytic Therapy; Treatment Outcome; Troponin I; Ventricular Dysfunction, Right

African Americans (AA) with systemic sclerosis (SSc) have a worse prognosis compared to Americans of European descent (EA). We conducted the current study to test the hypothesis that AA patients with SSc have more severe disease and poorer outcomes compared to EA patients when afflicted with pulmonary arterial hypertension (PAH). We studied 160 consecutive SSc patients with PAH diagnosed by right heart catheterization, comparing demographics, hemodynamics, and outcomes between AA and EA patients. The cohort included 29 AA and 131 EA patients with similar baseline characteristics except for increased prevalence of diffuse SSc in AA. AA patients had worse functional class (FC) (80% FC III-IV vs 53%; p = 0.02), higher brain natriuretic peptide (NT-pro-BNP) (5729 ± 9730 pg/mL vs 1892 ± 2417 pg/mL; p = 0.02), more depressed right ventricular function, a trend toward lower 6-minute walk distance (263 ± 111  m vs 333 ± 110  m; p = 0.07), and worse hemodynamics (cardiac index 1.95 ± 0.58 L/min/m vs 2.62 ± 0.80 L/min/m; pulmonary vascular resistance 10.3 ± 6.2 WU vs 7.6 ± 5.0 WU; p  < 0.05) compared with EA patients. Kaplan-Meier survival estimates for AA and EA patients, respectively, were 62% vs 73% at 2 years and 26% vs 44% at 5 years (p  > 0.05). In conclusion, AA patients with SSc-PAH are more likely to have diffuse SSc and to present with significantly more severe PAH compared with EA patients. AA patients also appear to have poorer survival, though larger studies are needed to investigate this association definitively.

Topics: Adult; Autoantibodies; Black or African American; Cardiac Catheterization; Echocardiography; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Peptide Fragments; Prevalence; Prognosis; Scleroderma, Systemic; Severity of Illness Index; United States; Ventricular Dysfunction, Right; White People

B-type natriuretic peptide (BNP) has not been evaluated in newborns with congenital diaphragmatic hernia (CDH). We hypothesized that BNP and severity of pulmonary hypertension (PH) would predict clinical outcome in these infants.. We measured BNP levels and assessed severity of PH by echocardiography at 1 d and 1 wk of life. Outcome was classified by status at 56 d (or prior discharge): Good (n = 13) if alive on room air and Poor (n = 14) if expired or receiving respiratory support. We estimated area under the curve (AUC) and 95% confidence interval (CI).. BNP levels were higher at 1 d in newborns with Poor outcome (median 220 pg/ml vs. 55 pg/ml, P < 0.01). At 1 wk, there was no significant difference in BNP level (median 547 pg/ml vs. 364 pg/ml, P = 0.70, for Poor and Good outcomes). At 1 d, BNP level predicted outcome (AUC = 0.91, 95% CI = 0.77-1.0), but this relationship dissipated by 1 wk (AUC = 0.55, 95% CI = 0.31-0.79). Severity of PH did not predict outcome at 1 d (AUC = 0.51, 95% CI = 0.27-0.74), but prediction improved at 1 wk (AUC = 0.80, 95% CI = 0.61-0.99).. BNP is a strong predictor of clinical outcome in newborns with CDH at 1 d of life.

Topics: Area Under Curve; Biomarkers; Female; Hernias, Diaphragmatic, Congenital; Hospital Mortality; Humans; Hypertension, Pulmonary; Infant; Infant Mortality; Infant, Newborn; Male; Natriuretic Peptide, Brain; Perinatal Death; Predictive Value of Tests; Prospective Studies; Risk Factors; ROC Curve; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography

Topics: Antioxidants; Biomarkers; Creatinine; Echocardiography, Doppler; Hemodynamics; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Pulmonary Circulation; Sensitivity and Specificity; Troponin T; Uric Acid

There is considerable interest in the pleiotropic effects of statins and their potential role in the treatment of pulmonary hypertension. Previous experimental findings indicate that a combination of lipophilic statins with phosphodiesterase type-5 inhibitor, sildenafil, can offer preventive effects on rat monocrotaline-induced pulmonary hypertension. The present study is aimed to assess whether therapeutic regimen provides any benefits. Seven days after pulmonary hypertension induction, hydrophilic rosuvastatin and sildenafil were given for 14 days to male Wistar outbred rats. Right ventricular pressure, right ventricle mass and three biomarkers were evaluated after 21 days: brain natriuretic peptide, high-density lipoprotein cholesterol and vascular endothelial growth factor. The present study demonstrates that administration of hydrophilic statin with sildenafil results in reduction of pulmonary vascular remodeling and right ventricular pressure. The results of biochemical measurements may suggest that statins play a positive role in right ventricle function or the process of angiogenesis in pulmonary hypertension development.

Topics: Animals; Antihypertensive Agents; Arterial Pressure; Biomarkers; Cholesterol, HDL; Disease Models, Animal; Drug Therapy, Combination; Fluorobenzenes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Monocrotaline; Natriuretic Peptide, Brain; Phosphodiesterase 5 Inhibitors; Piperazines; Pulmonary Artery; Purines; Pyrimidines; Rats, Wistar; Rosuvastatin Calcium; Sildenafil Citrate; Sulfonamides; Time Factors; Vascular Endothelial Growth Factor A; Vascular Remodeling; Vasodilator Agents; Ventricular Function, Right; Ventricular Pressure

Classically, biomarkers such as the natriuretic peptides (NPs) BNP/NT-proBNP are associated with the diagnosis of heart failure and hs-cTnT with acute coronary syndromes. NPs are also elevated in pulmonary hypertension. High pulmonary artery systolic pressure (PASP) is a key feature of high altitude pulmonary edema (HAPE), which may be difficult to diagnose in the field. We have previously demonstrated that NPs are associated with high PASP and the presence of acute mountain sickness (AMS) in a small cohort at HA. We aimed to investigate the utility of several common cardiac biomarkers in diagnosing high PASP and AMS.. 48 participants were assessed post-trekking and at rest at three altitudes: 3833 m, 4450 m, and 5129 m. NPs, hs-cTnT and hsCRP, were quantified using immunoassays, PASP was measured by echocardiography, and AMS scores were recorded.. Significant changes occurred with ascent in NPs, hs-cTnT, hsCRP (all p<0.001) and PASP (p=0.006). A high PASP (≥40 mm Hg) was associated with higher NPs, NT-proBNP: 137±195 vs. 71.8±68 (p=0.001); BNP 15.3±18.1 vs. 8.7±6.6 (p=0.001). NPs were significantly higher in those with AMS or severe AMS vs. those without (severe AMS: NT-proBNP: 161.2±264 vs. 76.4±82.5 (p=0.008)). The NPs correlated with hsCRP. cTnT increased with exercise at HA and was also higher in those with a high PASP (13.8±21 vs. 7.8±6.5, p=0.018).. The NPs and hs-cTnT are associated with high PASP at HA and the NPs with AMS.

Topics: Acute Disease; Adult; Altitude; Altitude Sickness; Biomarkers; Blood Pressure; C-Reactive Protein; Cohort Studies; Exercise; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mountaineering; Natriuretic Peptide, Brain; Natriuretic Peptides; Peptide Fragments; Pulmonary Artery; Rest; Troponin T

To explore the correlation between submaximal exercise measurements and peak oxygen uptake in patients with pulmonary arterial hypertension (PAH).. The clinical data were retrospectively analyzed for 106 patients with PAH from Affiliated Shanghai Pulmonary Hospital, Tongji University from October 2010 to October 2013. The examinations included routine pulmonary function test, N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walk test, right heart catheterization and cardiopulmonary exercise testing. And within the same period, matched 20 healthy subjects without smoking and cardiopulmonary diseases were selected as control group.. Peak oxygen uptake (P-VO2), anaerobic threshold (AT), oxygen uptake efficiency slope (OUES) and oxygen uptake efficiency plateau (OUEP) were significantly lower in patients with PAH than control group ((841 ± 257) vs (1 682 ± 284) ml/min, (661 ± 171) vs (1 041 ± 243) ml/min, 1.1 ± 0.4 vs 2.3 ± 0.4, 25.8 ± 5.2 vs 35.5 ± 4.0, respectively) (all P < 0.001). And the predicted parametric values (%pred) were also lower in PAH group than control group (all P < 0.001). While the lowest ventilation (VE)/CO2 output (VCO2) (L-VE/VCO2) and VE/VCO2 slope were significantly higher in PAH group than control group (50.5 ± 15.9 vs 30.5 ± 3.0 and 57.2 ± 23.2 vs 25.6 ± 2.8, both P < 0.001). Pearson correlation analysis showed, except for VE/VCO2 slope%pred, AT%pred, L-VE/VCO2%pred, OUES%pred and OUEP%pred were correlated with P-VO2 (all P < 0.001). According to multiple linear regression analysis, only AT%pred and OUES%pred were the independent predictors of P-VO2 (β = 0.394, 0.384, both P < 0.001) and OUES%pred might be better than AT%pred (the adjusted β = 0.674). When AT%pred < 58.0% or OUES%pred < 65.0%, exercise capacity in PAH declined obviously with the sensitivity was 92.3% and 96.2% and the specificity 81.2% and 75.5% respectively.. Exercise capacity in patients with PAH is significantly lower than healthy subjects. OUES%pred and AT%pred may be used as an independent predictor of exercise capacity. And OUES%pred may be more powerful.

Topics: Anaerobic Threshold; Exercise Test; Humans; Hypertension, Pulmonary; Multivariate Analysis; Natriuretic Peptide, Brain; Oxygen; Oxygen Consumption; Peptide Fragments; Pulmonary Artery; Respiratory Function Tests; Retrospective Studies

Pentraxin3 (PTX3) is a protein, which has multifaceted effects on innate immunity, angiogenesis, and vascular remodeling then could be a disease marker of acute myocardial infarction, heart failure, vasculitis. In addition, PTX3 has been recognized as a biomarker for pulmonary arterial hypertension, however whether it is the case in chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. Therefore, we investigated whether PTX3 would be a useful biomarker for detecting CTEPH with respect to differentiation from stable pulmonary thromboembolism (PTE), in comparison to other biomarkers.. Plasma PTX3 and brain natriuretic peptide (BNP) levels were measured in 70 patients with CTEPH at their first diagnostic right heart catheterization (CTEPH group) and in 20 patients with clinically stable PTE more than three months after the acute episode (control group). The levels of plasma C-reactive protein (CRP) and heart-type fatty acid-binding protein (H-FABP) were also analyzed to compare the diagnostic ability of these biomarkers.. The mean level of PTX3 (ng/mL) was significantly higher in the CTEPH group than in the control group (5.51±4.53 versus 2.01±0.96, respectively), and PTX3 levels had mild negative correlation with cardiac output. BNP levels were also higher in the CTEPH group and better correlated with pulmonary hemodynamics than PTX3. However, a receiver operating characteristic (ROC) curve showed PTX3 levels were better for detecting CTEPH, and could detect CTEPH patients with less severe pulmonary hemodynamics and low plasma BNP levels. There was no significant increase in CRP and H-FABP levels in the CTEPH patients.. Plasma PTX3 level was the most sensitive biomarker of CTEPH. Although plasma PTX3 levels did not correlate with the severity of the pulmonary hemodynamics compared to BNP, high levels in clinically stable patients following PTE should prompt a further work-up for CTEPH, which may lead to an early diagnosis.

Topics: Aged; Biomarkers; C-Reactive Protein; Endarterectomy; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Embolism; ROC Curve; Serum Amyloid P-Component

Topics: Aged; Chest Tubes; Comorbidity; Echocardiography; Female; Heart Failure; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Pleural Effusion; Pulmonary Atelectasis; Tomography, X-Ray Computed

Topics: Anemia, Sickle Cell; Anticoagulants; Antisickling Agents; Echocardiography, Doppler; Erythrocyte Transfusion; Humans; Hydroxyurea; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Tricuspid Valve

Chronic exposure to biomass fuel smoke has been implicated in the development of pulmonary hypertension and right ventricular pressure/volume overload through activation of inflammation, increase in vascular resistance, and endothelial dysfunction. We sought to compare N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and echocardiography-derived pulmonary artery systolic pressure (PASP) levels in a high-altitude population-based study in Peru with and without chronic exposure to biomass fuel smoke.. NT-pro-BNP levels were measured in 519 adults (275 with and 244 without chronic exposure to biomass fuel smoke). Participants answered sociodemographics and clinical history questionnaires, underwent a clinical examination and blood testing for cardiopulmonary biomarkers. PASP was measured in a subgroup of 153 (31%) subjects.. The study group consisted of 280 men (54%) and 239 women (46%). Average age was 56 years and average body mass index was 27 kg/m(2). In multivariable analysis, there was no association between chronic exposure to biomass fuel smoke and NT-pro-BNP (P = .31) or PASP (P = .31). In the subgroup in which both NT-pro-BNP levels and PASP were measured, there was strong evidence of an association between these two variables (ρ = 0.24, 95% CI 0.09-0.39; P = .003). We found that age, high sensitivity C-reactive protein, being male, and systolic blood pressure were positively associated with NT-pro-BNP levels whereas body mass index, low-density/high-density lipoprotein ratio, and Homeostasis Model of Assessment-Insulin Resistance were negatively associated (all P ≤ .02).. In this population-based study in a high-altitude setting, neither NT-pro-BNP levels nor echocardiography-derived PASP were associated with chronic exposure to biomass fuel smoke.

Topics: Adult; Age Factors; Aged; Altitude; Arterial Pressure; Biomass; Blood Pressure; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Cohort Studies; Echocardiography; Environmental Exposure; Female; Hemoglobins; Humans; Hypertension, Pulmonary; Insulin Resistance; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Peru; Pulmonary Artery; Sex Factors; Smoke; Ventricular Dysfunction, Right; Ventricular Pressure

To evaluate the contribution of activation of cytokines and renin-angiotensin-aldosterone system to heart remodeling in patients with chronic obstructive pulmonary disease in the course of a 2 year study and to estimate its relation to severe pulmonary hypertension.. 117 patients with COPD underwent measurement of TNFα, IL-6 levels and renin levels, spirometry and echocardiography (mean pressure in pulmonary artery, MPPA)). The data obtainedwere compared with the degree of remodeling of right and left ventricles. After 2 years 30 and 33 of the 63 patients were referred to groups with aggressive and moderate remodeling of the right ventricle respectively. Regressive analysis was used to detect predictors of aggressive remodeling.. Initial remodeling severity and rate showed stronger correlation with TNFα, IL-6 levels and renin levels than with MPPA. Multifactor analysis demonstrated that renin activity and creatinine level were the most reliable predictors of remodeling (p = 0.041 and 0.049 respectively).. Neurohormonal and imunno-inflammatory changes stimulate remodeling of right and left heart chambers. They independently affect myocardium and their influence is only partly mediated through exacerbation of pulmonary hypertension.

Topics: Aged; Disease Progression; Female; Humans; Hypertension, Pulmonary; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Pulmonary Disease, Chronic Obstructive; Pulmonary Heart Disease; Regression Analysis; Renin; Renin-Angiotensin System; Severity of Illness Index; Tumor Necrosis Factor-alpha; Ventricular Remodeling

Pulmonary arterial hypertension (PAH) still cannot be cured effectively, hence the search for novel treatments continues. The effects of sildenafil (25 mg/kg body weight) and fasudil (30 mg/kg body weight) given alone or in combination, on normalization of right ventricular pressure (RVP), right ventricle mass, as well as the levels of several biomarkers (HDL-C, BNP, VEGF-A), were assessed in a rat model of monocrotaline (MCT)-induced PAH. MCT (60 mg/kg body weight) induced clear PAH in male Wistar rats. After 21 days, a significant decrease in RVP accompanied by a reduction of right ventricular hypertrophy - a significant decrease in the right ventricle/left ventricle plus septum ratio - as a result of sildenafil or fasudil administration was assessed. The administration of fasudil and sildenafil alone or in combination caused a significant decrease in plasma BNP level as compared to MCT-treated rats. Fasudil alone or with sildenafil, but not sildenafil alone, significantly increased HDL-C level as compared to MCT-treated rats. Fasudil and sildenafil given alone or in combination caused a significant increase in plasma VEGF-A level as compared to rats exposed to MCT.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Cholesterol, HDL; Drug Therapy, Combination; Familial Primary Pulmonary Hypertension; Hemodynamics; Hypertension, Pulmonary; Male; Monocrotaline; Natriuretic Peptide, Brain; Phosphodiesterase 5 Inhibitors; Piperazines; Protein Kinase Inhibitors; Purines; Rats; Rats, Wistar; rho-Associated Kinases; Sildenafil Citrate; Sulfones; Vascular Endothelial Growth Factor A

N-terminal pro-brain natriuretic peptide (NT-proBNP), a pro-hormone secreted by the myocardium in response to various stimuli, was found to be correlated with several hemodynamic parameters in pulmonary hypertension associated with systemic sclerosis. We investigated plasma NT-proBNP levels and the relationships between NT-proBNP and several hemodynamic parameters in atrial septal defect (ASD) patients with or without pulmonary arterial hypertension (PAH). We found that plasma NT-proBNP level was significantly higher in PAH group compared with the control group (5495.4±388.4 pg/ml vs 4005.1±260.5 pg/ml, P<0.05). In a multiple regression model analysis, only mean pulmonary arterial pressure was an independent predictor of NT-proBNP (standardized coefficient=0.663, P=0.002). In the PAH group, only right atrial systolic pressure was found to be positively correlated with NT-proBNP, whereas other parameters were not found to be correlated with NT-proBNP. Our data suggests that NT-proBNP might also be a predictor of the severity of pulmonary hypertension in the ASD patients.

Topics: Adult; Case-Control Studies; Female; Heart Septal Defects, Atrial; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Regression Analysis; Young Adult

Pulmonary fibrosis is often complicated by pulmonary hypertension. Statins reduce fibroblast activity in vitro and pulmonary hypertension in vivo. We investigated whether Simvastatin exerts beneficial effects on pulmonary fibrosis and pulmonary hypertension in Bleomycin-treated rats in vivo.. Rats were randomly assigned to controls, Bleomycin, Bleomycin plus Simvastatin from day 1 to 28 and Bleomycin plus Simvastatin from day 13 to 28. 28 days after Bleomycin instillation, right ventricular systolic pressure (RVSP), right ventricular mass (RV/(LV+S)), right ventricular and circulating brain natriuretic peptide (BNP) levels were determined to assess pulmonary hypertension. Pulmonary hydroxyproline content (HPC), pulmonary connective tissue growth factor (CTGF) transcription and lung compliance (LC) were analysed to characterize pulmonary fibrosis. Exercise capacity was determined by treadmill tests.. Compared with controls, Bleomycin increased RVSP, RV/(LV+S), BNP levels, HPC and CTGF transcription and decreased LC significantly. Simvastatin administered from day 1 to 28 normalized all these parameters. Simvastatin administered from day 13 to 28 had no effect on HPC and LC, but reduced RV/(LV+S) significantly and induced a strong trend to lower RVSP and BNP levels. Exercise capacity was reduced by Bleomycin. Simvastatin significantly improved exercise intolerance in both treatment groups.. Simvastatin prevents the development of pulmonary fibrosis, but fails to attenuate already established pulmonary fibrosis. In contrast, it ameliorates pulmonary hypertension and thereby exercise capacity in the prevention and the treatment group regardless of its effects on pulmonary fibrosis. Whether statins are a treatment option in humans with pulmonary fibrosis needs to be investigated by further study.

Topics: Animals; Bleomycin; Hydroxyproline; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lung Compliance; Male; Motor Activity; Natriuretic Peptide, Brain; Pulmonary Fibrosis; Random Allocation; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Simvastatin

To investigate ghrelin levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and the association of ghrelin with N-terminal brain natriuretic peptide (N-BNP), endothelin-1 (ET-1) and nitric oxide (NO).. Plasma ghrelin, N-BNP, ET-1 and NO were measured, and echocardiography was performed in 20 IPAH patients and in 20 control subjects matched for age, sex and body mass index.. Plasma ghrelin and NT-proBNP levels were significantly higher in IPAH patients compared with values in control subjects (p < 0.05). In IPAH patients, ghrelin levels correlated positively with N-BNP (r = 0.616, p = 0.004), NO (r = 0.464, p = 0.039), right ventricle diameter (RVD; r = 0.485, p = 0.030) and pulmonary arterial systolic pressure (PASP; r = 0.591, p = 0.006). N-BNP levels correlated positively with RVD (r = 0.551, p = 0.012) and ET-1 (r = 0.451, p = 0.046).. Plasma ghrelin levels were elevated in IPAH. Increased ghrelin levels correlated positively with N-BNP, PASP, RVD and NO, and N-BNP levels correlated positively with RVD and ET-1. Pulmonary vascular pathology is a complex imbalance of opposing forces. Ghrelin may not only provide a novel prognostic biomarker for IPAH but also be a potential new therapeutic strategy.

Topics: Adult; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Endothelin-1; Familial Primary Pulmonary Hypertension; Female; Ghrelin; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Nitric Oxide; Peptide Fragments; Prognosis

The current study aimed to investigate the release of myocardial high-sensitive Troponin T (hsTnT) in patients with pulmonary arterial hypertension (PAH) in response to maximal physical exercise.. In 24 patients with PAH, symptom-limited cardiopulmonary exercise testing was performed. hsTnT was measured by the novel hsTnT assay with a lower limit of detection of 2 ng/L and a total imprecision of less than 10% at the 99th percentile value. hsTnT was related to NT-proBNP, WHO functional class and right ventricular (RV) function. Serial measurement was performed before and 30 min, 180 min, and 300 min after exercise. Healthy volunteers served as a control group.. In 21 PAH patients, hsTnT levels were detectable before exercise with a close correlation between hsTnT and NT-proBNP. hsTnT was detectable in all PAH patients after exercise and significantly increased from 7.5 ng/L at baseline to 14.62 ng/L after 300 min, whereas levels of NT-proBNP remained constant with time.. Using the novel hsTnT assay, the current study provides first evidence that hsTnT levels increase in PAH patients after maximal physical exercise, while levels of other biomarkers remain constant after exercise testing. This might provide new insights into pathophysiology and individual risk assessment in patients with PAH.

Topics: Adult; Aged; Biomarkers; Cohort Studies; Exercise; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Thromboembolism; Troponin T; Ventricular Function, Right; Walking

Topics: Adult; Altitude; Altitude Sickness; Biomarkers; Blood Pressure; Heart Rate; Humans; Hypertension, Pulmonary; Male; Mountaineering; Natriuretic Peptide, Brain; Troponin C

Increasing evidence implicates lymphocytes in pulmonary arterial hypertension (PAH) pathogenesis. Rats deficient in T-lymphocytes show increased propensity to develop PAH but when injected with endothelial progenitor cells are protected from PAH (a mechanism dependent on natural killer (NK) cells). A decreased quantity of circulating cytotoxic CD8+ T-lymphocytes and NK cells are now reported in PAH patients; however, the effect of lymphocyte depletion on disease outcome is unknown.. This prospective study analysed the lymphocyte profile and plasma brain natriuretic peptide (BNP) levels of patients with idiopathic PAH (IPAH), connective tissue disease-associated PAH (CTD-APAH) and matched healthy controls. Lymphocyte surface markers studied include: CD4+ (helper T-cell marker), CD8+ (cytotoxic T-cell marker), CD56/CD16 (NK cell marker) and CD19+ (mature B-cell marker). Lymphocyte deficiencies and plasma BNP levels were then correlated with clinical outcome.. Fourteen patients with PAH (9 IPAH, 5CTD) were recruited. Three patients were deceased at 1-year follow-up; all had elevated CD4 : CD8 ratios and deficiencies of NK cells and cytotoxic CD8+ T-lymphocytes at recruitment. Patients with normal lymphocyte profiles at recruitment were all alive a year later, and none were on the active transplant list. As univariate markers, cytotoxic CD8+ T-cell and NK cell counts were linked to short-term survival.. Deficiencies in NK cells and cytotoxic CD8+ T-cells may be associated with an increased risk of death in PAH patients. Further research is required in larger numbers of patients and to elucidate the mechanism of these findings.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; CD8-Positive T-Lymphocytes; Cell Count; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Killer Cells, Natural; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Survival Rate

Tadalafil, a once-daily phosphodiesterase type 5 inhibitor (PDE-5I), offers clinicians an alternative to sildenafil, a 3-times-daily (t.i.d.) PDE-5I for treatment of pulmonary arterial hypertension (PAH). However, there are limited data describing the risks and benefits or recommended methodology of switching patients from sildenafil to tadalafil.. Chart reviews were conducted on all World Health Organization group 1 patients on sildenafil for ≥ 3 months who transitioned to tadalafil with documented clinic visits and 6-min walk tests on both drugs. Most patients were transitioned by discontinuing sildenafil after the evening dose and initiating tadalafil 40 mg/day the next day. Data collected included demographics, PAH etiology, diagnostic hemodynamics, 6-min walk distance (6MWD), PDE-5I side effects, and concomitant medications. Data on B-type natriuretic peptide (BNP) levels were available for most patients also receiving endothelin receptor antagonists (ERAs).. Medical records from 98 patients were evaluated. Most patients (92%) were on sildenafil for > 1 year, and 78% were receiving sildenafil 80-100 mg t.i.d. Ninety-seven percent of patients (95/98) were successfully transitioned and maintained on 40 mg/day. With a mean duration on tadalafil therapy of 243 ± 127 days at the time of analysis, 6MWD was unchanged. Patient-reported adverse events included headache (4%) and heartburn (2%). There was minimal change in BNP levels in the subset of patients receiving an ERA concomitantly.. Transition from sildenafil to tadalafil 40 mg/day appears feasible without clinical deterioration or intolerable side effects. This study provides guidance to physicians considering transition from sildenafil to tadalafil for selecting patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carbolines; Endothelin Receptor Antagonists; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Retrospective Studies; Sildenafil Citrate; Sulfones; Tadalafil

Pulmonary arterial hypertension (PAH) is a rare, deadly condition. Although risk stratification is extremely important for assessment of prognosis and to guide therapy, there is lack of evidence concerning the role of novel biomarkers. In a pivotal study, we sought to comparatively investigate the predictive power of several new biomarkers in PAH.. Patients with prevalent PAH were enrolled in the study protocol, which included clinical, functional and echocardiographic assessment. Blood samples were collected at baseline for determination of NT-proBNP, CT-proET-1, MR-proANP, MR-proADM, copeptin and troponin I. Patients were clinically followed-up up to 12 months for first occurrence of hospital admission due to PAH-related clinical worsening, heart/lung transplantation or all-cause mortality.. Among the 28 included patients the pre-specified end-point occurred in 8 (29% event rate). There were higher baseline levels of CT-proET-1, copeptin, MR-proANP, NT-proBNP and troponin I in patients who reached the composite end-point. They also had larger right atria. In multivariate Cox regression, CT-proET-1 was the only biomarker associated with increased hazard of reaching the primary composite end-point (hazard ratio per tertile increase = 10.1; 95% CI 2.0 to 50.6).. CT-proET-1 provided prognostic information independent of other biomarkers. Importantly, we have provided the first evidence that CT-proET-1 may be superior to commonly used biomarkers.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Cohort Studies; Echocardiography; Endothelin-1; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Glycopeptides; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Regression Analysis; Risk Factors; Troponin I

This study sought to examine the relationships between right ventricular (RV) function, body composition, and prognosis in patients with advanced heart failure (HF).. Previous studies investigating HF-related cachexia have not examined the impact of RV function on body composition. We hypothesized that RV dysfunction is linked to weight loss, abnormal body composition, and worsened prognosis in advanced HF.. Subjects with advanced HF (n = 408) underwent prospective assessment of body composition (skinfold thickness, dual-energy X-ray absorptiometry), comprehensive echocardiography, and blood testing. Subjects were followed up for adverse events (defined as death, transplantation, or circulatory assist device).. Subjects with RV dysfunction (51%) had lower body mass index, lower fat mass index, and were more likely to display cachexia (19%). The extent of RV dysfunction correlated with greater antecedent weight loss and a lower fat/lean body mass ratio. Over a median follow-up of 541 days, there were 150 events (37%). Risk of event was greater in subjects with RV dysfunction (hazard ratio: 3.09 [95% confidence interval (CI): 2.18 to 4.45]) and cachexia (hazard ratio: 2.90 [95% CI: 2.00 to 4.12]) in univariate and multivariate analyses. Increased body mass index was associated with a lower event rate (HR per kg/m(2): 0.92 [95% CI: 0.88 to 0.96]), and this protection was mediated by a higher fat mass (0.91 [95% CI: 0.87 to 0.96]) but not a fat-free mass index (0.97 [95% CI: 0.92 to 1.03]).. RV dysfunction and cardiac cachexia often coexist, have additive adverse impact, and might be mechanistically interrelated. Wasting of fat but not of lean mass was predictive of adverse outcome, suggesting that fat loss is either a surrogate of enhanced catabolism or adipose tissue is cardioprotective in the context of HF.

Topics: Adiponectin; Age Factors; Body Composition; Body Fat Distribution; Body Mass Index; Cachexia; Echocardiography; Female; Follow-Up Studies; Heart Failure, Systolic; Heart Rate; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Severity of Illness Index; Ventricular Dysfunction, Right

To explore the role of peak oxygen consumption in assessment of heart function of patients with pulmonary hypertension.. From September 2010 to April 2012, 101 patients [29 male, mean age: (32.6 ± 11.4 )years] with pulmonary hypertension diagnosis by right heart catheterization were enrolled. Correlations among peak oxygen consumption, New York Heart Association (NYHA) class, NT-proBNP, 6 minute walking distance (6MWD) and cardiac index are analyzed.. There were 44 cases with NYHA class II (43.6%), 49 cases with NYHA class III (48.5%), mean 6MWD was (421 ± 91 )m, NT-proBNP was (1262 ± 816) ng/L, pulmonary vascular resistance was (1031 ± 582) dyn·s(-1)·cm(-5), CI was (3.5 ± 2.3) L·min(-1)·m(-2), peak oxygen consumption was( 13.8 ± 4.1)ml·min(-1)·kg(-1). 6MWD, pulmonary vascular resistance and peak oxygen consumption were related to CI (r = 0.299, -0.541, 0.341, respectively, all P < 0.05), but NYHA class and NT-proBNP were not correlated to CI. Multiple regression analysis demonstrated that peak oxygen consumption (B = 0.135, P = 0.004) but not 6MWD was correlated with CI after adjusting age, sex and pulmonary vascular resistance. ROC analysis found that the sensitivity and specificity using peak oxygen consumption <15.2 ml·min(-1)·kg(-1) as a cut-off value was 92.6% and 57.5%, respectively, for diagnosing severe heart dysfunction.. The correlation between peak oxygen consumption and CI is better than that of NYHA class, 6MWD, and NT-proBNP with CI. Peak oxygen consumption less than 15.2 ml·min(-1)·kg(-1) could be used to detect reduced CI in patients with pulmonary hypertension.

Topics: Adult; Exercise Test; Female; Heart; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Young Adult

To explore the exercise characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH).. From November 2010 to September 2012 , 76 consecutive IPAH patients and 24 healthy controls from Fuwai Cardiovascular Hospital were enrolled to undergo cardiopulmonary exercise testing. The exercise parameters were compared. Correlations among peak oxygen consumption, anaerobic threshold, peak oxygen pulse, New York Heart Association (NYHA) class, N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6 MWD) and cardiac index are analyzed in IPAH.. There were 21 males and 55 females in IPAH and 8 males and 16 females in controls. Their mean ages were (31.5 ± 10.6) and (35.5 ± 6.4) years respectively. Significant differences (P = 0.000) existed between two groups in peak oxygen consumption ((12.7 ± 3.3) vs (25.6 ± 5.8) ml·min(-1)·kg(-1)), anaerobic threshold ((9.8 ± 2.5) vs (16.7 ± 3.9) ml·min(-1)·kg(-1)), peak oxygen pulse ((5.3 ± 1.6) vs (9.9 ± 2.5) ml/bpm) and ventilator efficiency (slope of minute ventilation in relation to CO2 produced) ((42.6 ± 2.0) vs (25.5 ± 3.5)). In IPAH, peak oxygen consumption was significantly correlated with NYHA class (r = -0.509, P = 0.000), 6 MWD (r = 0.443, P = 0.002) and NT-proBNP levels (r = -0.423, P = 0.011). And anaerobic threshold was significantly correlated with NYHA class (r = -0.362, P = 0.002), 6MWD (r = 0.343, P = 0.004) and NT-proBNP levels (r = -0.275, P = 0.017). Peak oxygen pulse and ventilator efficiency were both correlated well with total pulmonary vascular resistance. Partial correlation analysis demonstrated that there were significant correlations among peak oxygen consumption, anaerobic threshold, NYHA class, NT-proBNP levels and 6MWD after adjusting for age, gender and weight.. Peak oxygen consumption and anaerobic threshold decrease ventilator efficiency in IPAH patients. Cardiopulmonary exercise testing is an invasive tool of assessing safely the function of IPAH patients.

Topics: Adult; Case-Control Studies; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Oxygen Consumption; Young Adult

To evaluate the application value of cardiopulmonary exercise testing in patients with chronic thromboembolic pulmonary hypertension (CTEPH).. A total of 116 consecutive patients admitted into the Cardiology Department of Fuwai Hospital.They were divided into 3 groups of CTEPH (n = 44), CPE (without pulmonary hypertension in chronic pulmonary embolism) (n = 24) and control (without pulmonary embolism or pulmonary hypertension) (n = 48) respectively. Their levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. Incremental cardiopulmonary exercise testing was performed to compare its differential results among 3 groups and evaluate the correlation between NT-proBNP and its parameters.. The body mass index (BMI) in the CTEPH group was lower than those in the CPE and control groups ((23.8 ± 3.9) vs (26.1 ± 3.6) and (26.7 ± 3.2) kg/m(2) ), both P < 0.05); the medical history in the CTEPH group was longer than those in the CPE and control groups ((58 ± 48) vs (12 ± 10) and (29 ± 25) months, both P < 0.05). The plasma concentrations of NT-proBNP in the CTEPH group were higher than those in the CPE and control groups ((1678 ± 1255) vs (577 ± 167) and (608 ± 247) pmol/L, both P < 0.05). All of them completed the test and there were no severe complications such as syncope or exacerbation of disease. Maximum oxygen consumption (VO2max), percentage of predicted maximum oxygen consumption (VO2 %), oxygen consumption in relation to body weight (VO2/kg), anaerobic threshold and O2 pulse in the CTEPH group were significantly lower than those in the CPE and control groups (P < 0.05). The ratios of dead space volume (VD) to tidal volume (VT) in the CTEPH and CPE groups were higher than those in the control group (P < 0.05). The plasma concentrations of NT-proBNP were inversely correlated with right ventricular internal diameter (r = -0.690, P = 0.000) and VO2/kg (r = -0.496, P = 0.000). The right ventricular internal diameter (β = 0.583, P = 0.000) and VO2/kg (β = 0.233, P = 0.032) were strong independent determinants of NT-proBNP.. As a reliable pathophysiological indictor of CTEPH, cardiopulmonary exercise testing may be used objectively and safely to evaluate the cardiopulmonary function of CTEPH patients.

Topics: Adult; Aged; Case-Control Studies; Chronic Disease; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pulmonary Embolism

To examine the correlation of the changes in the serum markers (C-reactive protein, endothelin-1, interleukin-6, and brain natriuretic peptide) with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension secondary to COPD.. A total of 174 COPD patients with acute exacerbation, admitted between February 2011 and February, 2013, were enrolled in this study, with 43 volunteers with normal pulmonary functions as controls. Pulmonary arterial pressure was determined by Doppler echocardiograph, and the severities (mild, moderate and severe) of PH secondary to COPD was evaluated. The levels of serum markers were determined using ELISA kits.. The levels of serum markers in patients with COPD was significantly elevated compared with those of the control subjects (P<0.05), and further increased in patients with pulmonary hypertension secondary to COPD (P<0.05). A positive correlation was found between these serum markers and pulmonary artery pressure in COPD patients with mild and moderate pulmonary hypertension. In patients with severe pulmonary hypertension, only the serum level of brain natriuretic peptide continued to increase with pulmonary artery pressure (P<0.05), and the other markers did not further increase.. Early and combined examination of these serum markers in patients with COPD can help to identify pulmonary hypertension in early stage and estimate the severity of pulmonary hypertension. Hemodynamic monitoring of the changes of these serum markers can be of important clinical value in the treatment of pulmonary hypertension secondary to COPD and in evaluation of the prognosis of COPD.

Topics: Aged; Biomarkers; Blood Pressure; C-Reactive Protein; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Interleukin-6; Male; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive

Pulmonary arterial hypertension (PAH) is a major cause of mortality in systemic sclerosis (SSc). Screening guidelines for PAH recommend multiple investigations, including annual echocardiography, which together have low specificity and may not be cost-effective. We sought to evaluate the predictive accuracy of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in combination with pulmonary function tests (PFT) (‘proposed’ algorithm) in a screening algorithm for SSc-PAH.. We evaluated our proposed algorithm (PFT with NT-proBNP) on 49 consecutive SSc patients with suspected pulmonary hypertension undergoing right heart catherisation (RHC). The predictive accuracy of the proposed algorithm was compared with existing screening recommendations, and is presented as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).. Overall, 27 patients were found to have pulmonary hypertension (PH) at RHC, while 22 had no PH. The sensitivity, specificity, PPV and NPV of the proposed algorithm for PAH was 94.1%, 54.5%, 61.5% and 92.3%, respectively; current European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines achieved a sensitivity, specificity, PPV and NPV of 94.1%, 31.8%, 51.6% and 87.5%, respectively. In an alternate case scenario analysis, estimating a PAH prevalence of 10%, the proposed algorithm achieved a sensitivity, specificity, PPV and NPV for PAH of 94.1%, 54.5%, 18.7% and 98.8%, respectively.. The combination of NT-proBNP with PFT is a sensitive, yet simple and non-invasive, screening strategy for SSc-PAH. Patients with a positive screening result can be referred for echocardiography, and further confirmatory testing for PAH. In this way, it may be possible to shift the burden of routine screening away from echocardiography. The findings of this study should be confirmed in larger studies.

Topics: Aged; Algorithms; Cohort Studies; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Respiratory Function Tests; Scleroderma, Systemic; Sensitivity and Specificity

To determine the levels of circulating copeptin in patients with pulmonary arterial hypertension (PAH), and to evaluate its relation with disease severity, outcome and response to treatment.. Vasopressin is a key regulator of body fluid homeostasis. The co-secreted protein copeptin serves as surrogate for plasma vasopressin levels and increases in acute and chronic left ventricular dysfunction. Copeptin has not been studied in PAH.. Serum copeptin levels were evaluated in a retrospective cohort of 92 treatment-naïve patients with PAH, 39 patients with normal right ventricular hemodynamics (diseased controls) and 14 apparently healthy individuals (healthy controls). In a second prospective cohort of 15 patients with PAH, serial changes of copeptin levels after initiation of PAH treatment were measured. Copeptin levels were compared with clinical, biochemical and hemodynamic parameters as well as response to treatment and clinical outcome.. Circulating copeptin levels were elevated in PAH patients compared to diseased controls (20.1 pmol/l vs. 5.1 pmol/l; p = 0.001). Baseline levels of copeptin correlated with NYHA functional class (r = 0.46; p = 0.01), 6 minute walking distance (r = -0.26; p = 0.04), NT-proBNP (r = 0.49, p = 0.01), creatinine (r = 0.39, p = 0.01) and estimated glomerular filtration rate (r = -0.32, p = 0.01). Copeptin levels did not correlate with hemodynamics but decreased after initiation of PAH therapy (p = 0.001). Elevated copeptin levels were associated with shorter survival (p < 0.001) and independent predictors of mortality in a multiple Cox regression analysis (HR1.4; 95% confidence interval 1.1-2.0; p = 0.02).. Patients with PAH had elevated copeptin levels. High circulating levels of copeptin were independent predictors of poor outcome, which makes copeptin a potentially useful biomarker in PAH.

Topics: Aged; Biomarkers; Case-Control Studies; Cohort Studies; Familial Primary Pulmonary Hypertension; Female; Glycopeptides; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Regression Analysis; Retrospective Studies; Severity of Illness Index

Six-minute walk distance (6MWD) and brain natriuretic peptide (BNP) levels at baseline and after initiation of treatment have been associated with survival in patients with pulmonary arterial hypertension. Our objective was to determine the individual and additive ability of pretreatment and posttreatment 6MWD and BNP to discriminate 2-year survival in patients with pulmonary arterial hypertension.. We included patients enrolled in two randomized clinical trials of ambrisentan who had 2-year follow-up (N 5 370). 6MWD and BNP were assessed before and after 12 weeks of treatment. Receiver operating characteristic curve analyses were performed to identify optimal cutoffs that defi ned subgroups with a high 2-year mortality. Classifi cation and regression tree analysis was used to determine the incremental prognostic value of combined assessments.. 6MWD at baseline and after 12 weeks of therapy were similarly discriminatory of 2-year survival (c-statistics 5 0.77 [95% CI 0.70-0.84] and 0.82 [95% CI 0.75-0.88], respectively), whereas change in 6MWD from baseline to week 12 was not discriminating. The same observation was true of BNP at baseline and after 12 weeks of therapy (c-statistics 5 0.68 [95% CI 0.60-0.76] and 0.74 [95% CI 0.66-0.82], respectively). After consideration of baseline 6MWD, there was no prognostic information added by the week 12 6MWD or BNP at either time point.. 6MWD and BNP values at baseline or week 12 identifi ed a population with an elevated risk of death at 2 years. A repeat assessment of 6MWD or BNP after 12 weeks of ambrisentan therapy did not provide additional prognostic information beyond that obtained from baseline values.

Topics: Adult; Aged; Antihypertensive Agents; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Phenylpropionates; Predictive Value of Tests; Prognosis; Pyridazines; Survival Rate; Treatment Outcome; Walking

The aim of this study was to explore whether the regional peak longitudinal (LS) and circumferential strains (CS) at the right ventricular (RV) free wall could be used to identify global RV dysfunction in relation to RV ejection fraction (RVEF) and plasma concentration of brain natriuretic peptide (BNP) in pulmonary hypertension (PH). A total of 37 consecutive patients diagnosed with PH and 13 healthy control subjects were included. Fast strain encoded and routine cine MRI was performed. The LS and CS at three RV levels were quantified and their relations with RVEF and BNP were investigated. Receiver operating characteristic (ROC) analysis was employed to assess the diagnostic utility of strain encoded MRI for the detection of low RVEF. Significant correlations with LS were observed for RVEF and BNP. Compared to CS, LS showed better correlation with RVEF. The mid-ventricular level of RV was the most sensitive site for evaluation of RV dysfunction. According to our ROC analysis, LS showed higher sensitivity and specificity to detect low RVEF. Compared to CS, LS showed stronger correlations with RVEF and BNP and could be a good detector of RV dysfunction in PH.

Topics: Adult; Aged; Biomarkers; Biomechanical Phenomena; Case-Control Studies; Female; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Observer Variation; Predictive Value of Tests; Reproducibility of Results; ROC Curve; Severity of Illness Index; Stroke Volume; Ventricular Dysfunction, Right; Ventricular Function, Right

Patients with pulmonary hypertension (PH) typically have exercise intolerance and limitation in climbing steps.. To explore the exercise physiology of step climbing in PH patients, on a laboratory-based step test.. We built a step oximetry system from an 'aerobics' step equipped with pressure sensors and pulse oximeter linked to a computer. Subjects mounted and dismounted from the step until their maximal exercise capacity or 200 steps was achieved. Step-count, SpO(2) and heart rate were monitored throughout exercise and recovery. We derived indices of exercise performance, desaturation and heart rate. A 6-min walk test and serum NT-proBrain Natriuretic Peptide (BNP) level were measured. Lung function tests and hemodynamic parameters were extracted from the medical record.. Eighty-six subjects [52 pulmonary arterial hypertension (PAH), 14 chronic thromboembolic PH (CTEPH), 20 controls] were recruited. Exercise performance (climbing time, height gained, velocity, energy expenditure, work-rate and climbing index) on the step test was significantly worse with PH and/or worsening WHO functional class (ANOVA, p < 0.001). There was a good correlation between exercise performance on the step and 6-min walking distance-climb index (r = -0.77, p < 0.0001). The saturation deviation (mean of SpO(2) values <95 %) on the step test correlated with diffusion capacity of the lung (ρ = -0.49, p = 0.001). No correlations were found between the step test indices and other lung function tests, hemodynamic parameters or NT-proBNP levels.. Patients with PAH/CTEPH have significant limitation in step climbing ability that correlates with functional class and 6-min walking distance. This is a significant impediment to their daily activities.

Topics: Activities of Daily Living; Adult; Aged; Analysis of Variance; Biomarkers; Case-Control Studies; Chi-Square Distribution; Exercise Test; Exercise Tolerance; Familial Primary Pulmonary Hypertension; Female; Heart Rate; Humans; Hypertension, Pulmonary; Linear Models; Lung; Male; Middle Aged; Motor Activity; Natriuretic Peptide, Brain; Oximetry; Oxygen; Peptide Fragments; Predictive Value of Tests; Signal Processing, Computer-Assisted; Walking

We sought to investigate the experimental therapeutic effects and mechanisms of iptakalim, a new adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP)) opener, on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and right heart ventricle remodeling in rats.. Rats were injected with a single dose (50 mg/kg, ip) of MCT and given iptakalim (1, 3, and 9 mg/kg·per d, orally [po]) or saline for 28 days. The hemodynamic and morphometric parameters were assessed. Tissue and plasma samples were collected for histological and molecular analysis.. Treatment with iptakalim at daily oral doses of 1, 3, and 9 mg/kg from the day of MCT injection attenuated the high right ventricle systolic pressure (RVSP) and the increased weight ratio of right ventricle (RV) to left ventricle (LV) plus septum (S) (RV/(LV+S)), decreased heart rate (HR) and decreased mean arterial pressure (MAP), inhibited the RV myocardial tissue cell apoptosis, and the RV myocardial cell B-type natriuretic peptide (BNP) protein expression. Iptakalim also decreased the serum levels of nitric oxide (NO), endothelin 1 (ET-1), BNP, and the levels of NO, ET-1, and tumor necrosis factor-alpha (TNF-α) in the lung tissue.. These results indicate that iptakalim prevents MCT-induced PAH and RV remodeling and its mechanisms are related to inhibiting the pathological increases in NO, ET-1, BNP, and TNF-α, and Iptakalim may be a promising candidate for the treatment of PAH.

Topics: Animals; Endothelin-1; Familial Primary Pulmonary Hypertension; Hemodynamics; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; KATP Channels; Lung; Male; Monocrotaline; Natriuretic Peptide, Brain; Nitric Oxide; Propylamines; Rats; Rats, Wistar

Noninvasive assessment of right heart function and hemodynamics in patients with pulmonary arterial hypertension (PAH) is most often performed at rest, whereas the symptoms, in general, present with exertion. Assessment during exertion is limited to symptom assessment and the 6-minute walk distance. We investigated the feasibility of obtaining echocardiographic data that could accurately reflect pulmonary artery pressures (PAP), particularly mean PAP and right ventricular function during exercise in patients with PAH.. We investigated right ventricular function and hemodynamics using echocardiography during symptom-limited exercise in 10 consecutive patients undergoing right heart catheterization (RHC) as part of their clinical evaluation for PAH. We further assessed these measurements for correlation with known predictors of outcome in PAH in an exploratory analysis.. We were able to successfully obtain complete right heart measurements by echocardiography, including mean PAP, in the majority (9 of 10) of the subjects. One patient had an incomplete tricuspid regurgitation jet at rest and with exercise. Echocardiographic pulmonary vascular resistance correlated with RHC cardiac output and brain natriuretic peptide level, whereas tricuspid annular plane systolic excursion during exercise correlated with right atrial pressure on RHC, brain natriuretic peptide, and 6-minute walk distance. Tricuspid regurgitation velocity and mean PAP with exercise correlated moderately with mean PAP and cardiac output by RHC.. Exercise echocardiography can provide meaningful data in patients with PAH, including measuring mean PAP. The presence of correlations in this small number of patients indicates promising targets for future investigation.

Topics: Adult; Aged; Blood Pressure; Cardiac Output; Echocardiography, Stress; Exercise Tolerance; Feasibility Studies; Female; Heart Ventricles; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Artery; Tricuspid Valve Insufficiency; Vascular Resistance; Ventricular Function, Right

Topics: Exercise Test; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Walking

Current guidelines for the treatment of patients with idiopathic pulmonary arterial hypertension (IPAH) recommend basing therapeutic decision-making on haemodynamic, functional and biochemical variables. Most of these parameters have been evaluated as risk predictors at the time of diagnosis. The aim of the present study was to assess the prognostic impact of changes in these parameters after initiation of targeted therapy. A cohort of 109 patients with IPAH who had undergone haemodynamic, functional and biochemical assessments at baseline and 3-12 months after initiation of pulmonary arterial hypertension (PAH)-targeted therapy, were followed for a median 38 months in order to determine predictors of mortality at baseline and during the course of their disease. Within the observation period, 53 (48.6%) patients died and four (3.7%) underwent lung transplantation. Kaplan-Meier estimates for transplantation-free survival were 92%, 67%, and 51% at 1, 3, and 5 yrs, respectively. Among baseline variables, 6-min walk distance, right atrial pressure, cardiac index, mixed-venous oxygen saturation (S(v,O(2))) and N-terminal-pro brain natriuretic peptide (NT-proBNP) were independent predictors of survival. During follow-up, changes in World Health Organization functional class, cardiac index, S(v,O(2)) and NT-proBNP proved significant predictors of outcome. When assigned to prognostic groups, improvements as well as deteriorations in these parameters after initiation of PAH-targeted therapy had a strong impact on survival. Measurements obtained at follow-up had a higher predictive value than variables obtained at baseline. Changes in established predictors of outcome during the course of the disease provide important prognostic information in patients with IPAH.

Topics: Adult; Aged; Atrial Function, Right; Cohort Studies; Endothelin Receptor Antagonists; Epoprostenol; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Lung Transplantation; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Prognosis; Prostaglandins; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Circulating cardiac troponins are markers of myocardial injury. We sought to determine whether cardiac troponin I (cTnI), measured by a sensitive assay, is associated with disease severity and prognosis in pulmonary arterial hypertension (PAH). cTnI was measured in 68 patients with PAH diagnostic category 1 in a research-based sensitive immunoanalyser with a lower limit of detection of 0.008 ng · mL(-1). The associations between cTnI and PAH severity and clinical outcomes were assessed using Chi-squared and Wilcoxon rank sum tests, Kaplan-Meier analysis and Cox regression models. cTnI was detected in 25% of patients. Patients with detectable cTnI had more advanced functional class symptoms, a shorter 6-min walk distance, more pericardial effusions, larger right atrial area, and higher B-type natriuretic peptide and C-reactive protein levels. 36-month transplant-free survival was 44% in patients with detectable cTnI versus 85% in those with undetectable cTnI. cTnI was associated with a 4.7-fold increased risk of death related to right ventricular failure or transplant (hazard ratio 4.74, 95% CI 1.89-11.89; p<0.001), even when adjusted individually for known parameters of PAH severity. Elevated plasma cTnI, even at subclinically detectable levels, is associated with more severe disease and worse outcomes in patients with PAH.

Topics: Adult; Biomarkers; C-Reactive Protein; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Pericardial Effusion; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Troponin I

To determine relationship of echocardiographic measures of pulmonary hypertension to lung function and inflammatory biomarkers in HIV-infected individuals.. Cross-sectional study of 116 HIV-infected outpatients.. Doppler-echocardiography and pulmonary function testing were performed. Induced sputum and plasma cytokines, sputum cell counts and differentials, markers of peripheral T-cell activation, and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. Univariate and multivariate analyses determined relationship of echocardiographic variables to pulmonary function, inflammation, and NT-proBNP.. Mean estimated pulmonary artery systolic pressure (PASP) was 34.3 mmHg (SD 6.9) and mean tricuspid regurgitant jet velocity (TRV) was 2.5 m/s (SD 0.32). Eighteen participants (15.5%) had PASP of at least 40 mmHg, and nine (7.8%) had TRV of at least 3.0 m/s. Elevated TRV was significantly associated with CD4 cell counts below 200 cells/μl and higher log HIV-RNA levels. Forced expiratory volume in 1 s (FEV(1)) percentage predicted, FEV(1)/forced vital capacity, and diffusing capacity for carbon monoxide (DLco) percentage predicted were significantly lower in those with elevated PASP or TRV. Sputum interleukin-8, peripheral interleukin-8, peripheral interferon-γ levels, and CD8(+) T-cell expression of CD69(+) were associated with increasing PASP and TRV. Log NT-proBNP was significantly higher with increasing PASP and TRV. Left ventricular function was not associated with PASP or TRV.. Echocardiographic manifestations of pulmonary hypertension are common in HIV and are associated with respiratory symptoms, more advanced HIV disease, airway obstruction, abnormal DLco, and systemic and pulmonary inflammation. Pulmonary hypertension and chronic obstructive pulmonary disease coexist in HIV and may arise secondary to common inflammatory mechanisms.

Topics: Biomarkers; CD4 Lymphocyte Count; Cross-Sectional Studies; Cytokines; Echocardiography, Doppler; Female; Forced Expiratory Volume; HIV Infections; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Respiratory Function Tests; Risk Factors; RNA, Viral; Sputum; Vital Capacity

In this study, we investigated the relationship between plasma B-type natriuretic peptide (BNP) levels and hemodynamics from cardiac catheterization in pediatric patients with atrial or ventricular septal defect. A total of 59 patients were studied including 80% of patients had Qp/Qs > 1.5 and 25% of patients had pulmonary hypertension. The mean BNP value and BNP z-score were 10.9 ± 11.2 pg/mL and -0.28 ± 1.7 (-2.85 to 3.29), respectively. There was a statistically significant linear correlation between BNP value and the size of defects (r = 0.303, p = 0.002) and a trend toward to positive correlation between BNP value and Qp/Qs ratio (r = 0.183, p = 0.166) among all patients. To identify patients with a Qp/Qs ratio >1.5, the sensitivity and specificity were 28%, 100% in all patients at a plasma BNP cut-off point of 15 pg/mL. We concluded that a BNP > 15 pg/mL would help identify patients who need further intervention.

Topics: Adolescent; Biomarkers; Cardiac Catheterization; Child; Child, Preschool; Female; Heart Atria; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Hemodynamics; Humans; Hypertension, Pulmonary; Infant; Male; Natriuretic Peptide, Brain; Sensitivity and Specificity

Submaximal exercise gas analysis may be a useful method to assess and track pulmonary arterial hypertension (PAH) severity. The aim of the present study was to develop an algorithm, using exercise gas exchange data, to assess and monitor PAH severity. Forty patients with PAH participated in the study, completing a range of clinical tests and a novel submaximal exercise step test, which lasted 6 minutes and incorporated rest (2 minutes), exercise (3 minutes), and recovery (1 minute) ventilatory gas analysis. Using gas exchange data, including breathing efficiency, end-tidal carbon dioxide, oxygen saturation, and oxygen pulse, a pulmonary hypertension gas exchange severity (PH-GXS) score was developed. Patients were retested after about 6 months. There was significant separation between healthy controls and patients with moderate PAH (World Health Organization [WHO] class I/II) and those with more severe PAH (WHO class III/IV) for breathing efficiency, end-tidal carbon dioxide, oxygen saturation, and oxygen pulse. The PH-GXS score was significantly correlated with WHO class (r = 0.51), 6-minute walking distance (r = -0.59), right ventricular systolic pressure (r = 0.49), log N-terminal pro-B-type natriuretic peptide (r = 0.54), and pulmonary vascular resistance (r = 0.71). The PH-GXS score remained unchanged in 22 patients retested (1.50 ± 0.92 vs 1.48 ± 0.94), as did WHO class (2.3 ± 0.8 vs 2.3 ± 0.8) and 6-minute walking distance (455 ± 120 vs 456 ± 103 m). Small individual changes were observed in the PH-GXS score, with 8 patients improving and 8 deteriorating. In conclusion, the PH-GXS score differentiated between patients with PAH and was correlated with traditional clinical measures. The PH-GXS score was unchanged in our cohort after 6 months, consistent with traditional clinical metrics, but individual differences were evident. A PH-GXS score may be a useful way to track patient responses to therapy.

Topics: Adult; Aged; Algorithms; Antihypertensive Agents; Biomarkers; Carbon Dioxide; Case-Control Studies; Cohort Studies; Drug Therapy, Combination; Endothelin Receptor Antagonists; Epoprostenol; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Phosphodiesterase 5 Inhibitors; Pulmonary Gas Exchange; Risk Assessment; Severity of Illness Index; Treatment Outcome; Walking

Late gadolinium enhancement (LGE) occurs at the right ventricular (RV) insertion point (RVIP) in patients with pulmonary hypertension (PH) and has been shown to correlate with cardiovascular magnetic resonance (CMR) derived RV indices. However, the prognostic role of RVIP-LGE and other CMR-derived parameters of RV function are not well established. Our aim was to evaluate the predictive value of contrast-enhanced CMR in patients with PH.. RV size, ejection fraction (RVEF), and the presence of RVIP-LGE were determined in 58 patients with PH referred for CMR. All patients underwent right heart catheterization, exercise testing, and N-terminal pro-brain natriuretic peptide (NT-proBNP) evaluation; results of which were included in the final analysis if performed within 4 months of the CMR study. Patients were followed for the primary endpoint of time to clinical worsening (death, decompensated right ventricular heart failure, initiation of prostacyclin, or lung transplantation).. Overall, 40/58 (69%) of patients had RVIP-LGE. Patients with RVIP- LGE had larger right ventricular volume index, lower RVEF, and higher mean pulmonary artery pressure (mPAP), all p < 0.05. During the follow-up period of 10.2 ± 6.3 months, 19 patients reached the primary endpoint. In a univariate analysis, RVIP-LGE was a predictor for adverse outcomes (p = 0.026). In a multivariate analysis, CMR-derived RVEF was an independent predictor of clinical worsening (p = 0.036) along with well-established prognostic parameters such as exercise capacity (p = 0.010) and mPAP (p = 0.001).. The presence of RVIP-LGE in patients with PH is a marker for more advanced disease and poor prognosis. In addition, this study reveals for the first time that CMR-derived RVEF is an independent non-invasive imaging predictor of adverse outcomes in this patient population.

Topics: Adult; Aged; Biomarkers; Blood Pressure; Cardiac Catheterization; Chi-Square Distribution; Chicago; Contrast Media; Disease Progression; Exercise Test; Female; Gadolinium DTPA; Heart Failure; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Pulmonary Artery; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Ventricular Dysfunction, Right; Ventricular Function, Right

N-terminal pro-brain natriuretic peptide (NT-proBNP) is secreted by cardiac ventricular myocytes upon pressure and volume overload and is a prognostic marker to monitor the severity of precapillary pulmonary hypertension and the extent of right heart failure.. The impact of physical exercise on NT-proBNP levels in patients with left heart disease was demonstrated previously. No data regarding patients with isolated right heart failure and the influence of acute exercise on NT-proBNP serum levels exist.. Twenty patients with precapillary pulmonary hypertension were examined. Hemodynamic parameters were measured during right heart catheterization. Serum NT-proBNP of patients was measured at rest, after a 6-min walking test, during ergospirometry and during recovery, all within 7 h. Significant differences in sequential NT-proBNP values, relative changes compared to values at rest and the correlation between NT-proBNP and obtained parameters were assessed.. At rest, the mean serum level of NT-proBNP was 1,278 ± 998 pg/ml. The mean level of NT-proBNP at maximal exercise was increased (1,592 ± 1,219 pg/ml), whereas serum levels decreased slightly during recovery (1,518 ± 1,170 pg/ml). The relative increase of serum NT-proBNP during exercise correlated with pulmonary vascular resistance (r = 0.45; p = 0.026) and cardiac output (r = -0.5; p = 0.015).. In this study, we demonstrated acute changes in NT-proBNP levels due to physical exercise in a small group of patients with precapillary pulmonary hypertension. Our results also confirm the predominant usefulness of NT-proBNP as an intraindividual parameter of right heart load.

Topics: Adult; Aged; Exercise; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Vascular Resistance

Pulmonary hypertension (PH) is associated with progressive impairment of right ventricular function, reduced exercise capacity and a poor prognosis. Little is known about the prevalence, clinical manifestation and impact of atrial fibrillation (AF) on cardiac function in PH.. In a four year single-centre retrospective analysis 225 patients with confirmed PH of various origins were enrolled to investigate the prevalence of AF, and to assess the clinical manifestation, 6-minute walk distance, NT-proBNP levels, echocardiographic parameters and hemodynamics obtained by right heart catheterization in PH with AF.. AF was prevalent in 31.1%. In patients with PH and AF, parameters of clinical deterioration (NYHA/WHO functional class, 6-minute walk distance, NT-proBNP levels) and renal function were significantly compromised compared to patients with PH and sinus rhythm (SR). In the total PH cohort and in PH not related to left heart disease occurrence of AF was associated with an increase of right atrial pressure (RAP) and right atrial dilatation. While no direct association was found between pulmonary artery pressure (PAP) and AF in these patients, right ventricular function was reduced in AF, indicating more advanced disease. In PH due to left heart failure the prevalence of AF was particularly high (57.7% vs. 23.1% in other forms of PH). In this subgroup, left atrial dilatation, increase of pulmonary capillary wedge pressure, PAP and RAP were more pronounced in AF than in SR, suggesting that more marked backward failure led to AF in this setting.. PH is associated with increased prevalence of AF. Occurrence of AF in PH indicates clinical deterioration and more advanced disease.

Topics: Aged; Atrial Fibrillation; Atrial Function, Left; Cardiac Catheterization; Echocardiography; Exercise Test; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; Ventricular Function, Left

Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are rare causes of pulmonary hypertension. There is no proven medical therapy to treat these diseases, and lung transplantation is thought to be the only cure. Administration of vasodilators including epoprostenol sometimes causes massive pulmonary edema and could be fatal in these patients.. Eight patients were treated with epoprostenol for 387.3±116.3 days (range, 102-1,063 days), who were finally diagnosed with PVOD or PCH by pathological examination. The maximum dose of epoprostenol given was 55.3±10.7 ng·kg(-1)·min(-1) (range, 21.0-110.5 ng·kg(-1)·min(-1)). With careful management, epoprostenol therapy significantly improved the 6-min walk distance (97.5±39.2 to 329.4±34.6 m, P<0.001) and plasma brain natriuretic peptide levels (381.3±136.8 to 55.2±14.4 pg/ml, P<0.05). The cardiac index significantly increased from 2.1±0.1 to 2.9±0.3 L·min(-1)·m(-2) (P<0.05). However, pulmonary artery pressure and pulmonary vascular resistance were not significantly reduced. For 4 patients, epoprostenol therapy acted as a bridge to lung transplantation. For the other patients who had no chance to undergo lung transplantation, epoprostenol therapy was applied for 528.0±216.6 days and the maximum dose was 63.9±19.0 ng·kg(-1)·min(-1).. This study data suggest that cautious application of epoprostenol can be considered as a therapeutic option in patients with PVOD and PCH.

Topics: Adolescent; Adult; Antihypertensive Agents; Biomarkers; Blood Pressure; Child; Epoprostenol; Exercise Tolerance; Female; Hemangioma, Capillary; Humans; Hypertension, Pulmonary; Japan; Lung Neoplasms; Lung Transplantation; Male; Natriuretic Peptide, Brain; Pulmonary Veno-Occlusive Disease; Recovery of Function; Time Factors; Treatment Outcome; Vascular Resistance; Vasodilator Agents

Because few have reported the prognostic significance of cardiac magnetic resonance imaging (CMR) for idiopathic pulmonary arterial hypertension (IPAH), in this study we evaluated the value of CMR measurements as a prognostic predictor of IPAH before starting intravenous prostacyclin therapy.. A total of 121 consecutive CMR studies for evaluating right ventricular (RV) function were reviewed. Forty-one patients were diagnosed with IPAH and served as the study group. Factors, such as age, sex, New York Heart Association functional class (NYHAFC), 6-min walk test, plasma brain natriuretic peptide level, serum uric acid level and CMR measurements were analyzed as predictors of first hospitalization and death. The mean follow-up period was 1,350±769 days. Nine patients were hospitalized because of heart failure, and 4 patients died from cardiopulmonary causes. The univariate analyses suggested that the left ventricular (LV) mass index, the left and right ventricular end-diastolic volume indices (LVEDVI, RVEDVI), the LV and RV end-systolic volume indices (LVESVI, RVESVI) and NYHAFC predicted the risk for hospitalization and that RVEDVI, RVESVI and NYHAFC predicted mortality. The multivariate analyses suggested that RVEDVI and NYHAFC are independent predictors of both hospitalization and mortality. The effects of RVEDVI and NYHAFC on hospitalization were not substantially affected by the concomitant medication.. In IPAH patients, the RVEDVI predicts both hospitalization for right heart failure and mortality before initiating intravenous prostacyclin therapy.

Topics: Adult; Antihypertensive Agents; Biomarkers; Epoprostenol; Exercise Test; Exercise Tolerance; Familial Primary Pulmonary Hypertension; Female; Heart Failure; Hospitalization; Humans; Hypertension, Pulmonary; Japan; Magnetic Resonance Imaging; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Uric Acid; Vasodilator Agents; Ventricular Function, Left; Ventricular Function, Right; Young Adult

The information needed to diagnose pulmonary arterial hypertension (PAH) in dogs based on N-terminal pro B-type natriuretic peptide (NT-proBNP) and atrial natriuretic peptide (ANP) levels is unclear. In this study, serial changes in plasma NT-proBNP and ANP concentrations were evaluated in association with the development of chronic embolic pulmonary hypertension (CEPH). Six Beagle dogs underwent percutaneous pulmonary artery catheterization. CEPH was induced by the repeated injection of 300 μm microspheres into the pulmonary artery via the catheter. Measured peak systolic pulmonary arterial pressure (PAPs) was elevated up to 80 mm Hg at 90 days by repeated injection of microspheres. Echocardiographic examination showed significant increase in the main pulmonary artery enlargement, right ventricular dilation, transtricuspid late diastolic flow, and ventricular late diastolic myocardial velocity. Plasma concentrations of NT-proBNP and ANP were significantly increased by microsphere-induced severe CEPH, but not by mild CEPH. Measured PAPs correlated weakly with plasma NT-proBNP and ANP concentrations (r=0.63 and 0.69, respectively) and with several echocardiographic variables. Our results indicated that plasma ANP and NT-proBNP responded to severe PAH, but that they were not sensitive for mild PAH.

Topics: Animals; Atrial Natriuretic Factor; Disease Models, Animal; Dog Diseases; Dogs; Familial Primary Pulmonary Hypertension; Female; Hypertension, Pulmonary; Male; Microspheres; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Pulmonary Embolism; Ultrasonography

We present the case of a 72-year-old male with chronic phase myeloid leukemia. Elevation of the pulmonary artery pressure due to nilotinib therapy was noted. This effect on pulmonary artery pressure was nilotinib dose dependent.

Topics: Aged; Antineoplastic Agents; Echocardiography, Doppler; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pyrimidines

Pulmonary hypertension is becoming a recognized complication of the hereditary and acquired haemolytic anaemias, associated with a poor prognosis. Recently we reported that patients with paroxysmal nocturnal haemoglobinuria (PNH) have high levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker associated with both right and left ventricular dysfunction and cardiac dysfunction. In the current study we evaluated a cohort of patients (N = 29) with haemolytic PNH for elevated pulmonary artery systolic pressure and cardiac function by Doppler-echocardiography. Of the 29 patients, eight were further studied using cardiac magnetic resonance imaging (MRI), as well as two additional patients (number of patients studied using cardiac MRI = 10). Plasma from the first cohort (N = 29) demonstrated intravascular haemolysis associated with a 12-fold increase in median nitric oxide (NO) consumption when compared with healthy volunteers (P < 0·001). Doppler echocardiography demonstrated normal left ventricular function and elevated pulmonary artery systolic pressure in 41% of patients. Cardiac MRI from the second cohort (N = 10) demonstrated depressed right ventricular function in 80% of PNH patients tested, and 60% had findings suggestive of subclinical small pulmonary emboli. Together, these data suggest a high prevalence of haemolysis-associated NO scavenging, Doppler-estimated systolic pulmonary hypertension, and depressed right ventricular function in patients with PNH.

Topics: Adolescent; Adult; Aged; Echocardiography, Doppler; Heart; Hemoglobinuria, Paroxysmal; Humans; Hypertension, Pulmonary; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Function, Right; Young Adult

 Heart failure (HF) is a growing health care problem in the world. Secondary pulmonary venous hypertension is usually observed in patients with end‑stage heart failure..  The main purpose of the study was to evaluate the relationships between N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP) levels and the markers of secondary venous pulmonary hypertension in patients referred for heart transplantation (HTX). .  This retrospective analysis included 35 patients (32 men, 3 women; median age, 55.0; interquartile range [IQR] 12.0 years). The study group consisted of all consecutive patients referred for HTX, in whom the right‑heart catheterization using the Swan‑Ganz catheter was performed at the same time as the measurement of NT‑proBNP levels..  A high median value of NT‑proBNP (3187.0; IQR 2964.0 pg/ml) and elevated pulmonary pressure were observed in the study group. There was a significant correlation between NT‑proBNP levels and the values of systolic, mean, and diastolic pulmonary artery pressure (r = 0.5, P = 0.001; r = 0.5, P = 0.001; r = 0.5, P = 0.002; respectively) as well as cardiac output (r = -0.4, P = 0.007). There was also a positive correlation between pulmonary artery resistance and NT‑proBNP levels (r = 0.5, P = 0.006)..  In our study population, the median value of NT‑proBNP levels exceeded the normal range 25 times. There was a correlation between the markers of secondary pulmonary hypertension and cardiac output and NT‑proBNP levels. Elevated NT‑proBNP levels in patients with end‑stage HF may be associated with significant secondary venous pulmonary hypertension.

Topics: Adult; Aged; Biomarkers; Female; Heart Failure; Heart Transplantation; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies

Brain natriuretic peptide (BNP) levels are lower in obese patients with left ventricular failure than in their comparably ill, leaner counterparts. The effect of obesity on BNP in patients with pulmonary arterial hypertension (PAH) is unknown. We reviewed our prospective PAH registry data collected from November 2001 to December 2007 for patients undergoing right heart catheterization who met the criteria for PAH and had the BNP level and body mass index determined at baseline. The median BNP level for the lean, overweight, and obese patients was 285 pg/ml (interquartile range 131 to 548), 315 pg/ml (interquartile range 88 to 531), and 117 pg/ml (interquartile range 58 to 270), respectively (p = 0.029). A greater body mass index was associated with a lower BNP level, adjusted for age, gender, New York Heart Association functional class, hypertension, coronary artery disease, and mean right atrial and pulmonary arterial pressures (p <0.001). No statistically significant differences were found among the groups in age, race, medical co-morbidities, underlying etiology of PAH, use of vasoactive medications, New York Heart Association functional class, echocardiographic parameters, or pulmonary function. Obese patients had greater right atrial and pulmonary artery pressures. Increased BNP was associated with worse survival in the lean and overweight patients only. In conclusion, the BNP levels are attenuated in obese patients with PAH despite similar or worse hemodynamics or functional class compared to lean or overweight patients and should therefore be interpreted with caution.

Topics: Body Mass Index; Cardiac Catheterization; Echocardiography; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Obesity; Overweight; Prospective Studies; Survival Analysis; Thinness

The cardiac biomarker NT-proBNP indicates cardiac load in terms of myocardial wall stress. The objective of the study was to compare the results of NT-proBNP measurements in healthy dogs and dogs with dyspnea as well as asymptomatic dogs with heart murmur with the literature.. Between April 2007 and December 2007 dogs with dyspnea of non-cardiac origin (n=11), dogs with dyspnea of cardiac origin (n=18) and asymptomatic dogs with heart murmur (n=22) were included. Twelve clinically healthy dogs served as a control group. All animals underwent cardiologic examination including echocardiography and measurement of serum NT-proBNP concentration. Serum was centrifuged and frozen within 30 minutes and was stored frozen until analysis was performed.. Median NT-proBNP concentration in healthy dogs was 240 pmol/l (range 131-546 pmol/l). Dogs with dyspnea and primary respiratory disease displayed a median NT-proBNP concentration of 876 pmol/l (range 97-2614 pmol/l). In patients with dyspnea of non-cardiac origin, there was a difference in the values of NT-proBNP of dogs with and without pulmonary hypertension diagnosed by echocardiography. Dogs with dyspnea of cardiac origin displayed a median NT-proBNP concentration of 2000 pmol/l (range 137-2614 pmol/l). Low normal NT-proBNP values were only found in patients with pericardial effusion. Median NT-proBNP concentration in asymptomatic dogs with heart murmur was 698.5 pmol/l (range 121-2614 pmol/l). Considerably increased values were particularly measured in asymptomatic patients with severe congenital heart disease.. NT-proBNP represents a useful additional diagnostic parameter in veterinary clinical cardiology to assess the severity of cardiac disease. Interpretation must take into consideration the clinical picture of the patient, as dogs with severe arrhythmias, sepsis and pulmonary thromboembolism may display high NT-proBNP levels without congestive heart failure. Our results indicate the following cut-off values: <500 pmol/l: no relevant cardiac load; 500-900 pmol/l: moderate cardiac load; >900 pmol/l: severe cardiac load.

Topics: Animals; Biomarkers; Case-Control Studies; Dog Diseases; Dogs; Dyspnea; Echocardiography; Female; Heart Diseases; Heart Murmurs; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index

Pulmonary arterial hypertension is a major cause of mortality in systemic sclerosis. N-terminal pro-brain natriuretic peptide (NT-proBNP) has emerged as a candidate biomarker that may enable the early detection of systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). The objective of our study was to incorporate NT-proBNP into a screening algorithm for SSc-PAH that could potentially replace transthoracic echocardiography (TTE) as a more convenient and less costly "first tier" test.. NT-proBNP levels were measured in patients from four clinical groups: a group with right heart catheter (RHC)-diagnosed SSc-PAH before commencement of therapy for PAH; a group at high risk of SSc-PAH based on TTE; a group with interstitial lung disease; and systemic sclerosis (SSc) controls with no cardiopulmonary complications. NT-proBNP levels were compared by using ANOVA and correlated with other clinical variables by using simple and multiple linear regression. ROC curve analyses were performed to determine the optimal cut point for NT-proBNP and other clinical variables in prediction of PAH.. NT-proBNP was highest in the PAH group compared with other groups (P < 0.0001), and higher in the risk group compared with controls (P < 0.0001). NT-proBNP was positively correlated with systolic pulmonary artery pressure (PAP) on TTE (P < 0.0001), and mean PAP (P = 0.013), pulmonary vascular resistance (P = 0.005), and mean right atrial pressure (P = 0.006) on RHC. A composite model wherein patients screened positive if NT-proBNP was ≥ 209.8 pg/ml, and/or DLCOcorr was < 70.3% with FVC/DLCOcorr ≥ 1.82, had a sensitivity of 100% and specificity of 77.8% for SSc-PAH.. We have proposed a screening algorithm for SSc-PAH, incorporating NT-proBNP level and PFTs. This model has high sensitivity and specificity for SSc-PAH and, if positive, should lead to TTE and confirmatory testing for PAH. This screening algorithm must be validated prospectively.

Topics: Adult; Age of Onset; Aged; Algorithms; Area Under Curve; Biomarkers; Case-Control Studies; Early Diagnosis; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Scleroderma, Systemic; Sensitivity and Specificity

Increased filling pressures, or congestion, cause symptoms of heart failure and lead to hospitalizations. A higher rate of hospitalizations determines higher mortality. The most reliable way to decrease admissions is to monitor for signs of congestion, by history and exam, intracardiac pressures or biomarkers, and to modify treatment based on these data. The role of congestion is best understood by comparison of heart failure with preserved and reduced ejection fraction. The morbidity and mortality in both conditions is almost identical. Decreased cardiac output and ventricular remodeling play a major role in patients with decreased ejection fraction but not in those with preserved ejection fraction. The key factor that is present in both conditions and determines their similarity is congestion. Decongestion, or fluid removal, is the most effective treatment for heart failure regardless of ejection fraction. Being the driving force of heart failure, congestion should be the focus of clinical and hemodynamic monitoring and therapy.

Topics: Cardiac Output, Low; Cardio-Renal Syndrome; Diuretics; Heart Failure; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Pressure; Ventricular Remodeling

Pulmonary hypertension (PH) worsens the prognosis in chronic obstructive pulmonary disease (COPD). The diagnosis of PH is established by right heart catheterisation (RHC), while echocardiography can be used for screening. We aimed to asses the outcome of echocardiographic screening for PH in a group of stable COPD out-patients, and to evaluate NT-proBNP as a first line screening tool. Criteria for PH on echocardiography were a tricuspid regurgitation pressure gradient > 40 mmHg, a tricuspid annular plane systolic excursion < 1.8 cm or right ventricular dilatation. Positively screened patients were asked to undergo RHC. Results (Mean ± SEM): 16 of 117 patients (14%) had PH on echocardiography. They had a higher mortality (hazard ratio for death: 2.7 ± 1.3, p = 0.037) and lower six minute walk test (224 ± 33 vs. 339 ± 15, p = 0.006). NT-proBNP below 95 ng/l excluded PH on echocardiography with a negative predictive value of 100 (95% CI: 89-100%). RHC was obtained in six patients screened positive. In three of these, PH was not confirmed.. Signs of PH on echocardiography as defined here was found in 14% and had prognostic significance in COPD. A value of NT-proBNP less than 95 ng/l may be used to exclude signs of PH.

Topics: Aged; Biomarkers; Cardiac Catheterization; Echocardiography; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Mass Screening; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Spirometry; Tricuspid Valve Insufficiency

Radiofrequency ablation is first-line therapy for atrial flutter (AFL). There are no studies of ablation in patients with severe pulmonary arterial hypertension (PAH).. Consecutive patients with severe PAH (systolic pulmonary artery pressure >60 mmHg) and AFL referred for ablation were evaluated. Patients with complex congenital heart disease were excluded.. A total of 14 AFL ablation procedures were undertaken in 12 patients. A total of 75% of patients were female; mean age 49 ± 12 years. SPAP prior to ablation was 99 ± 35 mmHg. Baseline 6-minute walk distance was 295 ± 118 m. ECG demonstrated a typical AFL pattern in only 42% of cases. Baseline AFL cycle length was longer in PAH patients compared to controls (295 ± 53 ms vs 252 ± 35 ms, P = 0.006). Cavotricuspid isthmus dependence was verified in 86% of cases. Acute success was obtained in 86% of procedures. SPAP decreased from 114 ± 44 mmHg to 82 ± 38 mmHg after ablation (P = 0.004). BNP levels were lower postablation (787 ± 832 pg/mL vs 522 ± 745 pg/mL, P = 0.02). Complications were seen in 14%. A total of 80% (8/10) of patients were free of AFL at 3 months; 75% (6/8) at 1 year.. Ablation of AFL in severe PAH patients is feasible, with good short- and intermediate-term success rates. The ECG pattern is not a reliable marker of isthmus dependence. The SPAP and BNP levels may decrease postablation. AFL may be a marker of poor outcomes in patients with PAH with a 1-year mortality rate of 42% in this study. This rate is higher than expected in the general PAH population.

Topics: Adult; Aged; Arterial Pressure; Atrial Flutter; Biomarkers; Catheter Ablation; Chi-Square Distribution; Electrocardiography; Electrophysiologic Techniques, Cardiac; Exercise Test; Exercise Tolerance; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Pulmonary Artery; Recurrence; Retrospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome

Most of the deaths among patients with severe pulmonary arterial hypertension (PAH) are caused by progressive right ventricular (RV) pathological remodeling, dysfunction, and failure. Nicorandil can inhibit the development of PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling has been unclear.. RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT). RV systolic pressure (RVSP) was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP) ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochemical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD) reversed these beneficial effects of nicorandil in MCT-injected rats.. Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV pressure overload but also by inhibiting apoptosis in cardiomyocytes through the activation of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels. The use of a mitoK(ATP) channel opener such as nicorandil for PAH-associated RV remodeling and dysfunction may represent a new therapeutic strategy for the amelioration of RV remodeling during the early stages of PAH.

Topics: Animals; Antihypertensive Agents; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Enzyme-Linked Immunosorbent Assay; Hypertension, Pulmonary; In Situ Nick-End Labeling; Natriuretic Peptide, Brain; Nicorandil; Proto-Oncogene Proteins c-bcl-2; Rats; Ventricular Remodeling

In chronic thromboembolic pulmonary hypertension (CTEPH), right ventricular (RV) dysfunction is associated with increased morbidity and mortality following pulmonary endarterectomy. Plasma brain natriuretic peptide (BNP) levels were previously shown to correlate with RV (dys)function. We hypothesized that BNP can be used as a non-invasive biomarker to identify patients at 'high risk' for postoperative morbidity and mortality.. We studied the postoperative outcome in 73 consecutive patients. Patients were divided into three groups based on previously determined cut-off levels: BNP <11.5, indicating normal RV function (ejection fraction [EF] ≥45%), BNP >48.5 pmol/l, indicating RV dysfunction (right ventricular ejection fraction <30%) and BNP 11.5-48.5 pmol/l. Postoperative 'bad outcome' was defined as the presence of either residual pulmonary hypertension (PH) or (all-cause) mortality.. Plasma BNP >48.5 pmol/l was shown to be an independent predictor of 'bad outcome'. Compared with BNP <11.5 pmol/l, BNP >48.5 pmol/l identified patients at higher risk for (all-cause) mortality (17 vs 0%; P = 0.009) and residual PH (56 vs 20%; P < 0.004). Also, the durations of mechanical ventilation and intensive care unit stay were significantly longer in patients with BNP >48.5 pmol/ml.. Plasma BNP levels may be of use as a non-invasive biomarker reflecting RV dysfunction, next to other well-recognized (invasive) parameters, for better preoperative risk stratification of CTEPH patients.

Topics: Adolescent; Adult; Aged; Biomarkers; Endarterectomy; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Intensive Care Units; Length of Stay; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Pulmonary Embolism; Respiration, Artificial; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Up-Regulation; Ventricular Dysfunction, Right; Ventricular Function, Right; Young Adult

Pulmonary hypertension (PH) is an important complication to interstitial lung disease (ILD). The aim of the present study was to investigate the relation of NT-proBNP, fibrin D-dimer, troponin-T, uric acid and exhaled nitric oxide (NO) to the presence of PH and mortality in ILD.. In a previously described cohort of 212 ILD patients of whom 29 had PH, levels of the above mentioned biomarkers were analyzed as routine tests.. A value of NT-proBNP below 95 ng/l had a negative predictive value for PH of 99% (95% CI: 94-100). Values of troponin-T were higher in patients with PH (median (inter quartile range) = 9 (9-20) vs. 9(9-10) ng/l), and the odds ratio (OR) for PH was increased in patients with abnormal levels of uric acid (OR (95% CI) = 3.1(1.1-8.8)). NT-proBNP and troponin-T values above the 50(th) percentile, and uric acid and fibrin D-dimer values above the 90th percentile were each associated with increased mortality.. A value of NT-proBNP below 95 ng/l may be used as a rule-out test for PH in ILD, while an abnormal value of uric acid is a risk factor for PH. NT-proBNP, troponin-T, uric acid and fibrin D-dimer have prognostic value in ILD patients, while exhaled levels of NO do not seem to predict PH or mortality.

Topics: Biomarkers; Cross-Sectional Studies; Fibrin Fibrinogen Degradation Products; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Natriuretic Peptide, Brain; Nitric Oxide; Peptide Fragments; Prognosis; Pulmonary Fibrosis; ROC Curve; Troponin T; Uric Acid

The REgistry of Pulmonary Hypertension Associated with Rheumatic Disease (REOPARD) was established in Korea. The baseline data are described from the second year of the registry's operation.. Patients with a connective tissue disease (CTD) who met the modified definition of the WHO group I pulmonary arterial hypertension (PAH) were enrolled. PAH was defined as a systolic pulmonary arterial pressure> 40 mmHg by echocardiography or mean pulmonary arterial pressure> 25 mmHg by right heart catheterization. Hemodynamic parameters and clinical data such as demographics, functional class, underlying disease, organ involvement, laboratory tests and current treatment were recorded.. A total of 321 patients were enrolled during the 2-year study period from 2008 to 2010. The mean age of the patients at registration was 51.9 years and 87.5% were female. Most patients were diagnosed by echocardiography and only 24 patients (7.5%) underwent cardiac catheterization. Exertional dyspnea was present in 63.6% of patients and 31.8% were New York Heart Association class III or IV. Among the patients, systemic lupus erythematosus accounted for 35.3%, systemic sclerosis 28.3%, rheumatoid arthritis 7.8%, overlap syndrome 9.0%, and mixed connective tissue disease 5.9%. There were no significant differences in hemodynamics, functional class, diffusing capacity and N-terminal pro-brain natriuretic peptide levels between the disease subgroups. Treatments consisted of calcium antagonists (57.0%), endothelin antagonists (32.7%), prostanoids (27.1%), phosphodiesterase-5 inhibitors (14.3%) and combinations (37.4%).. Compared with previous studies, the results showed some differences: underlying diseases, functional status and treatments. This may be due to differences in ethnic background and diagnostic methods of our study.

Topics: Adult; Aged; Arthritis, Rheumatoid; Data Collection; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Lupus Erythematosus, Systemic; Male; Middle Aged; Mixed Connective Tissue Disease; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Diffusing Capacity; Registries; Republic of Korea; Retrospective Studies; Rheumatic Diseases; Scleroderma, Systemic

To evaluate the efficiency and safety of intravenous infusion of levosimendan in patients with idiopathic pulmonary hypertension (IPH) and its clinical, hemodynamic, and neurohumoral effects.. The study included 9 patients (mean age 31.8 +/- 8.7 years) with Functional Class III and IV IPH and severe right ventricular failure (RVF). Levosimendan was administered as dropwise intravenous infusion. The patients' general condition, blood pressure, heart rate, and 6-minute walk test results were assessed at baseline and 24 hours after levosimendan infusion, and then following 12 weeks. The time course of changes in blood neurohumoral mediators was determined and transthoracic echocardiography performed.. At 24 hours after initiation of levosimendan infusion, there were substantial reductions in pulmonary artery systolic pressure, mean pulmonary artery pressure, mean right atrial pressure, and pulmonary vascular resistance. There was a significant increase in exercise tolerance. The blood exhibited lower norepinephrine and NT-proBNP and higher epinephrine concentrations. At 12 weeks after termination of levosimendan infusion, the improved functional status was preserved in the patients with IPH. There were no noticeable changes in the achieved key hemodynamic parameters. Only one patient needed re-administration of the drug 12 weeks later. The achieved changes in vasoactive mediators were retained 12 weeks following levosimendan infusion. Levosimendan treatment was not followed by clinically relevant adverse reactions requiring infusion termination and therapy discontinuation.. 24-hour intravenous levosimendan infusion in patents with FC III-IV IPH and severe RVF causes positive changes in the key hemodynamic parameters and neurohumoral status of the patients and promotes stabilization in those with IPH at 12-week follow-up.

Topics: Adult; Blood Pressure; Cardiotonic Agents; Echocardiography; Epinephrine; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Heart Rate; Humans; Hydrazones; Hypertension, Pulmonary; Infusions, Intravenous; Male; Natriuretic Peptide, Brain; Norepinephrine; Peptide Fragments; Pyridazines; Severity of Illness Index; Simendan; Ventricular Dysfunction, Right; Young Adult

Chronic thromboembolic pulmonary hypertension leads to pulmonary hypertension and right-sided heart failure. The purpose of this study was to investigate the efficacy of percutaneous transluminal pulmonary angioplasty (PTPA) for the treatment of chronic thromboembolic pulmonary hypertension.. Twenty-nine patients with chronic thromboembolic pulmonary hypertension underwent PTPA. One patient had a wiring perforation as a complication of PTPA and died 2 days after the procedure. In the remaining 28 patients, PTPA did not produce immediate hemodynamic improvement at the time of the procedure. However, after follow-up (6.0 ± 6.9 months), New York Heart Association functional classifications and levels of plasma B-type natriuretic peptide significantly improved (both P<0.01). Hemodynamic parameters also significantly improved (mean pulmonary arterial pressure, 45.3 ± 9.8 versus 31.8 ± 10.0 mm Hg; cardiac output, 3.6 ± 1.2 versus 4.6 ± 1.7 L/min, baseline versus follow-up, respectively; both P<0.01). Twenty-seven of 51 procedures in total (53%), and 19 of 28 first procedures (68%), had reperfusion pulmonary edema as the chief complication. Patients with severe clinical signs and/or severe hemodynamics at baseline had a high risk of reperfusion pulmonary edema.. PTPA improved subjective symptoms and objective variables, including pulmonary hemodynamics. PTPA may be a promising therapeutic strategy for the treatment of chronic thromboembolic pulmonary hypertension.. URL: http://www.umin.ac.jp. Unique identifier: UMIN000001572.

Topics: Aged; Angioplasty, Balloon; Arterial Pressure; Biomarkers; Chronic Disease; Familial Primary Pulmonary Hypertension; Female; Hospital Mortality; Humans; Hypertension, Pulmonary; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Artery; Pulmonary Edema; Pulmonary Embolism; Recovery of Function; Reperfusion Injury; Risk Factors; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

To explore the relationship between serum uric acid levels and patient conditions and prognosis in idiopathic pulmonary arterial hypertension (IPAH).. A total of 76 IPAH patients confirmed by right heart catheterization were enrolled consecutively and followed up until the endpoint of all-cause death. Their baseline data were recorded and analyzed by Spearman's rank test and independent t-test. And the follow-up outcomes were analyzed with Kaplan-Meier plots.. There were 27 males and 49 females with a mean age of 29.7 ± 9.7 years. They were classified into World Health Organization functional class (WHO-FC)II (n = 28), class III (n = 45) and class IV (n = 3). Their baseline mean pulmonary artery pressure was (65 ± 16) mm Hg, pulmonary vascular resistance (1677 ± 669) dyn×s(-1)×cm(-5), pulmonary capillary wedge pressure (9.6 ± 5.0) mm Hg, mean right atrial pressure (9.8 ± 6.1) mm Hg, cardiac index (2.07 ± 0.57) L ×min(-1)× m(-2) and serum uric acid (391 ± 103) µmol/L. The correlation analysis indicated that the serum level of uric acid correlated positively with right ventricular diameter (r = 0.28, P = 0.018) and negatively with CI (r = -0.34, P = 0.003). Independent t-test results indicated that the patients with a higher level of uric acid were apt to have a worse WHO-FC, and the higher level uric acid group (serum uric acid > 416.5 µmol/L) had a relative higher level of WHO-FC, NT-proBNP and endothelin-1. A lower level of CI denoted more severe conditions and prognosis. Survival analysis indicated that the serum level of uric acid could strongly predict survival in IPAH patients with over time and those with a high level of uric acid had a worse prognosis.. The serum level of uric acid correlates significantly with patient conditions and prognosis in IPAH. And a higher serum level of uric acid predicts worse conditions and prognosis.

Topics: Adult; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Prognosis; Uric Acid; Young Adult

Current guidelines recommend right heart catheterisation (RHC) in symptomatic patients at risk of pre-capillary pulmonary hypertension (PH) with echocardiographic systolic pulmonary artery pressures ≥ 36 mmHg. Growing awareness for PH, a high prevalence of post-capillary PH and the inability to distinguish between pre- and post-capillary PH by echocardiography have led to unnecessary RHCs. The aim of our study was to assess whether standard noninvasive diagnostic procedures are able to safely exclude pre-capillary PH. Data from 251 patients referred for suspicion of pre-capillary PH were used to develop a noninvasive diagnostic decision tree. A prospectively collected data set of 121 consecutive patients was utilised for temporal validation. According to the decision tree, patients were stratified by the presence or absence of an electrocardiographic right ventricular strain pattern (RVS) and serum N-terminal brain natriuretic peptide (NT-proBNP) levels below and above 80 pg·mL⁻¹. In the absence of RVS and elevated NT-proBNP, none of the patients in the prospective validation cohort were diagnosed with pre-capillary PH by RHC. Combining echocardiography with the diagnostic algorithm increased specificity to 19.3% (p = 0.0009), while sensitivity remained at 100%. Employing ECG and NT-proBNP on top of echocardiography helps recognise one false positive case per five patients referred with dyspnoea and echocardiographic suspicion of PH, while not missing true pre-capillary PH.

Topics: Adult; Aged; Algorithms; Cardiac Catheterization; Cohort Studies; Electrocardiography; Female; Heart Ventricles; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Retrospective Studies; Sensitivity and Specificity; Ultrasonography

To describe the survival rate in a cohort of systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) and to evaluate possible predictors for SSc-PAH in a cohort of SSc patients.. Thirty patients with SSc-PAH and 150 SSc patients without PAH were included. Survival and survival on therapy were calculated. Clinical features at baseline were correlated to the risk for development of PAH during follow-up.. The 1-, 2-, 3-, and 4-year survival rates were 86, 59, 39, and 22%, respectively, from diagnosis of PAH. The hazard ratio for total mortality in the SSc-PAH group was 3.2 [95% confidence interval (CI) 1.8-5.7] compared to SSc without PAH (p < 0.001). Risk factors at baseline for the development of PAH were: limited skin involvement, low diffusing capacity of the lung for carbon monoxide (DL(CO)), high N-terminal pro-brain natriuretic peptide (NTProBNP), increased estimated systolic pulmonary arterial pressure (ESPAP), and the presence of teleangiectases. Severe peripheral vascular disease requiring iloprost treatment during follow-up was associated with an eightfold increased risk of PAH.. Despite modern treatment and yearly screening by echocardiography, the survival in SSc-PAH is still low in our cohort. The identified risk factors should be assessed to select patients eligible for right heart catheterization (RHC) to make an earlier diagnosis.

Topics: Adult; Aged; Blood Pressure; Carbon Monoxide; Case-Control Studies; Female; Humans; Hypertension, Pulmonary; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Scleroderma, Systemic; Survival Rate; Sweden

The pathogenesis of chronic mountain sickness (CMS) may involve vasoactive peptides. The aim of this study was to investigate associations between CMS and levels of B-type natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and endothelial nitric oxide synthase (eNOS). A total of 24 patients with CMS and 50 control subjects residing at 4,300 m participated in this study. Mean pulmonary arterial pressure (mPAP) was measured by echocardiography. Serum BNP, VEGF, ET-1, and eNOS were measured. Receiver operator characteristic curves to assess the balance of sensitivity and specificity for CMS were constructed. As a result, patients with CMS had significantly greater mPAP compared with controls and had lower arterial O(2) saturation (Sa(O(2))). Both BNP and ET-1 correlated positively with mPAP and negatively with Sa(O(2)), whereas serum VEGF levels were inversely correlated with Sa(O(2)); eNOS correlated negatively with mPAP and positively with Sa(O(2)). Median concentrations of BNP were greater in patients with CMS compared with those without CMS: 369 pg/ml [interquartile range (IQR) = 336-431] vs. 243 pg/ml (IQR = 216-279); P < 0.001. Similarly, concentrations of VEGF [543 pg/ml (IQR = 446-546) vs. 243 pg/ml (IQR = 216-279); P < 0.001] and ET-1 [14.7 pg/ml (IQR = 12.5-17.9) vs. 11.1 pg/ml (IQR = 8.7-13.9); P = 0.05] were higher in those with CMS compared with those without, whereas eNOS levels were lower in those with CMS [8.90 pg/ml (IQR 7.59-10.8) vs. 11.2 pg/ml (9.13-13.1); P < 0.001]. The areas under the receiver operator characteristic curves for diagnosis of CMS were 0.91, 0.93, 0.77, and 0.74 for BNP, VEGF, ET-1, and eNOS, respectively. In age- and biomarker-adjusted logistic regression, BNP and VEGF were positively predictive of CMS, whereas eNOS was inversely predictive. In conclusion, severe chronic hypoxemia and consequent pulmonary hypertension in patients with CMS may stimulate release of natriuretic peptides and angiogenic cytokines. These vasoactive peptides may play an important role in the pathogenesis and clinical expression of CMS and may indicate potential prognostic factors in CMS that could serve as targets for therapeutic trials or clinical decision making.

Topics: Adult; Altitude Sickness; Blood Pressure; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type III; Oxygen; Pulmonary Artery; ROC Curve; Sensitivity and Specificity; Ultrasonography; Vascular Endothelial Growth Factors

To determine plasma B-type natriuretic peptide (BNP) levels in children with heart diseases before medical or surgical treatment for monitoring therapeutic efficacy in an observational prospective clinical trial at tertiary care centre.. In 522 paediatric patients at an age of 6.4 ± 5.2 years (mean ± SD; range: 14 days-18 years) with congenital heart disease (CHD), cardiomyopathies (CMP) or pulmonary arterial hypertension (PAH), plasma BNP levels were evaluated before and under treatment.. Most types of heart disease are associated with increased mean plasma BNP levels before treatment, with highest values in children with CMP (BNP 6165 pg/mL in dilated CMP vs. 817 pg/mL in hypertrophic, vs. 1236 pg/mL in restrictive CMP, each p < 0.05). Children with PAH showed a significant decrease in BNP levels under medical treatment (mean BNP 981 pg/mL before vs. 26 pg/mL under treatment, p < 0.05). Children with univentricular CHD undergoing surgical staged palliation showed a significant decrease in BNP levels after bidirectional cavopulmonary anastomosis (BDCP) (BNP 109 pg/mL before vs. 70 pg/mL after BDCP, p < 0.05).. Plasma BNP levels are elevated in children with heart disease before treatment and are a useful laboratory parameter under treatment during long-term follow-up.

Topics: Adolescent; Cardiomyopathies; Child; Child, Preschool; Female; Heart Defects, Congenital; Heart Ventricles; Hemodynamics; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Male; Natriuretic Peptide, Brain; Prospective Studies; Statistics as Topic; Statistics, Nonparametric

To explore the potential role of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the assessment of patients with connective tissue diseases (CTD) associated pulmonary arterial hypertension (PAH).. Thirty patients with CTD associated PAH were evaluated by WHO function, echocardiography, right heart catheterization and blood biomarkers. All the clinical data was analyzed statistically.. All patients [age (39.5 ± 11.6) yr] were female. Both NT-proBNP and BNP were significantly increased and significantly correlated (all P < 0.05) respectively with mean pulmonary arterial pressure (r = 0.53 and r = 0.40), right arterial pressure (r = 0.55 and r = 0.42), pulmonary vascular resistance (r = 0.69 and r = 0.61), cardiac index (r = -0.58 and r = -0.46), mixed venous blood oxygen saturation (r = -0.62 and r = -0.54), pericardial effusion (r = 0.46 and r = 0.43), right atrial sizes (r = 0.40 and 0.53, and r = 0.39 and 0.45) and right ventricular size (r = 0.55 and r = 0.37). Furthermore, NT-proBNP, but not BNP, significantly correlated with WHO function class (r = 0.55).. Blood NT-proBNP and BNP were elevated in patients with CTD associated PAH and paralleled the extent of function class, pulmonary hemodynamic changes and right ventricular remodeling.

Topics: Adult; Connective Tissue Diseases; Familial Primary Pulmonary Hypertension; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Vascular Resistance; Ventricular Remodeling

Currently available endothelin receptor antagonists for treating pulmonary arterial hypertension block either the endothelin (ET) receptor A or both A and B receptors. Transition from one endothelin receptor antagonist to another may theoretically alter side-effects or efficacy. We report our experience of a transition from sitaxsentan to ambrisentan, both predominant ET(A) receptor antagonists, in pulmonary arterial hypertension patients.. At Baylor Pulmonary Hypertension Center, 18 patients enrolled in the open-label extension phase of the original sitaxsentan studies (Sitaxsentan To Relieve ImpaireD Exercise) were transitioned to ambrisentan (from July 2007 to September 2007) at the time of study closure. Pre-transition (PreT), 1 month (1Mth) and 1 year (1Yr) post-transition assessments of 6-minute walk distance (6MWD), brain naturetic peptide (BNP) levels, WHO functional class (WHO FC), Borg dyspnea score (BDS), oxygen saturation, liver function, and peripheral edema were compared.. 6MWD was 356 ± 126 m at PreT, 361 ± 125 m at 1Mth, and 394 ± 114 m at 1Yr (mean ± SD). There was no difference in the walk distance at 1Mth and 1Yr post transition compared with PreT (P=0.92, 0.41 respectively). Oxygen saturation was no different at 1Mth and 1Yr to PreT level (P=0.49 and P=0.06 respectively). BNP was 178 ± 44 pg/mL at PreT, 129 ± 144 pg/mL at 1Mth and 157 ± 201 at 1Yr. Peripheral edema was present in 7/18 patients at PreT, in 8/16 patients at 1Mth, and in 6/13 patients at 1Yr post transition. Proportions of patients with edema over these 3 time points did not change significantly (P=0.803). At 1Yr, 2 patients had died, 1 had undergone lung transplantation, 1 had relocated, and 1 patient was started on intravenous prostacyclin therapy. Over 3 points (baseline, 1 month, and 1 year), there was no significant change in function class (P=0.672).. Our limited data suggest that ET(A) receptor antagonists can be switched from one to another with sustained exercise capacity and maintained WHO FC with no increase in incidence of peripheral edema.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Drug Substitution; Dyspnea; Edema; Endothelin A Receptor Antagonists; Exercise Test; Exercise Tolerance; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Isoxazoles; Liver Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Phenylpropionates; Pyridazines; Retrospective Studies; Texas; Thiophenes; Time Factors; Treatment Outcome; Walking

Soluble TWEAK is a member of the TNF-alpha family of cytokines that has been shown to predict mortality in patients with heart failure. Pulmonary artery hypertension is a devastating disease, in which right ventricular function has been shown to be the major determinant of prognosis. In this hypothesis-generating study, we sought to evaluate the potential usefulness of sTWEAK in the prediction of disease severity in patients with pulmonary artery hypertension. We therefore conducted a retrospective analysis of sTWEAK serum levels in 95 stable patients with PAH. For all patients data on hemodynamic parameters, biomarkers and functional exercise tests were available. Compared to controls, patients with PAH showed significantly decreased levels of sTWEAK [median 314 pg/ml (interquartile range 217-473 pg/ml) vs. 405 (321-496 pg/ml); PAH vs. controls; P < 0.0001]. Soluble TWEAK levels were inversely correlated with NYHA class, pulmonary artery pressure, pulmonary vascular resistance, NT-proBNP, and troponin T levels and directly correlated with cardiac index, reduced 6-min walk test distances, and peak oxygen consumption. ROC curve analysis of sTWEAK levels in PAH patients revealed a cutoff value of 306 pg/ml for sTWEAK to be predictive of a reduced exercise capacity (6-min walk test <300 m) in patients with PAH with a similar predictive value compared to NT-proBNP. Intraindividual serial evaluation of sTWEAK revealed the potential of sTWEAK as follow-up marker in patients with PAH. In our hypothesis-generating study, sTWEAK was closely correlated to hemodynamic, functional, and serological indices of outcome in patients with PAH. Further prospective studies are needed to determine the role of sTWEAK as potential biomarker in patients with PAH.

Topics: Biomarkers; Blood Pressure; Cytokine TWEAK; Down-Regulation; Exercise Test; Exercise Tolerance; Familial Primary Pulmonary Hypertension; Female; Germany; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Predictive Value of Tests; Prognosis; Pulmonary Artery; Retrospective Studies; ROC Curve; Severity of Illness Index; Troponin T; Tumor Necrosis Factors; Vascular Resistance

In addition to N-terminal pro-brain natriuretic peptide (NT-proBNP), red cell distribution width (RDW), growth differentiation factor (GDF)-15, interleukin (IL)-6 and creatinine are all potential circulating prognostic biomarkers in pulmonary arterial hypertension (PAH).. To establish the relative prognostic utility of these biomarkers in patients with idiopathic PAH (IPAH) and to identify independent prognostic markers in this disease.. Circulating RDW, GDF-15, IL-6, creatinine and NT-proBNP levels were determined in 139 patients with IPAH (mean follow-up 4.0±2.4 years) and 40 age- and sex-matched healthy volunteers. Coincident clinical data and baseline haemodynamic measurements were also analysed.. All the biomarkers except creatinine correlated with a 6 min walk distance (6MWD; p<0.05), and all but NT-proBNP correlated with WHO functional class (p<0.01). GDF-15, creatinine and NT-proBNP correlated with mean right atrial pressures and cardiac index. RDW outperformed other biomarkers in receiver operating characteristic (ROC) analysis (area under the curve 0.820). Sensitive (>80%) ROC-derived cut-off points of RDW (15.7%, p=0.001), GDF-15 (779 pg/ml, p<0.001), IL-6 (2.5 pg/ml, p=0.019), creatinine (80.5 μmol/l, p=0.010) and NT-proBNP (491 fmol/ml, p<0.001), all predicted survival in patients with IPAH over time. All the plasma biomarkers analysed predicted survival in Cox regression analysis, as did clinical and haemodynamic parameters. However, only RDW predicted survival independently of NT-proBNP and 6MWD.. Circulating RDW, GDF-15, IL-6, creatinine and NT-proBNP levels are all related to disease severity and may be used to predict survival in patients with IPAH. RDW added significant prognostic value to measurements of NT-proBNP and exercise capacity and may prove valuable in a multiple biomarker approach to disease stratification.

Topics: Adult; Antihypertensive Agents; Biomarkers; Cell Size; Creatinine; Epidemiologic Methods; Erythrocytes; Familial Primary Pulmonary Hypertension; Female; Growth Differentiation Factor 15; Hemodynamics; Humans; Hypertension, Pulmonary; Interleukin-6; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Treatment Outcome

The aim of this study was to prospectively evaluate the prevalence of pulmonary hypertension (PH) in patients with idiopathic pulmonary fibrosis (IPF). One hundred thirty-nine patients (101 male, mean age = 68.6 ± 9 years), with confirmed IPF and who were admitted to eight Pulmonary Departments in Greece between November 2005 and December 2006 were included in the study. Pulmonary artery systolic pressure (PASP) was estimated by echocardiography, and PH was defined as PASP > 36 mmHg. We compared demographics, pulmonary function tests, NYHA functional status, 6-min walk distance (6MWD), B-type natriuretic peptide (BNP), PaO(2), and P(A-a)O(2) at rest data between patients with PH and without PH (PASP ≤ 36 mmHg). Increased estimated right ventricular systolic pressure was present in 55% of patients (mean PASP = 47.1 ± 11.2 mmHg vs. 30.3 ± 3.8 mmHg, respectively). Patients with PH had a lower but not statistically significant DL(CO) (47.1 ± 18.8 vs. 52.5 ± 20.1), lower PaO(2) at rest (64.6 ± 12.2 vs. 71.1 ± 11.3, P = 0.004), and lower mean 6MWD (282 ± 118 vs. 338 ± 91, P = 0.007). Significant differences were also observed in the NYHA functional status between the two groups (P = 0.02). Statistically significant correlations were observed between PASP and PaO(2) at rest (r = -0.331, P = 0.00), P(A-a)O(2) at rest (r = 0.494, P = 0.00)(,) 6MWD (r = -0.264, P = 0.01), SpO(2) at rest (r = -0.293, P = 0.00), SpO(2) at the end of exercise (r = -0.364, P = 0.00), and also BNP values (r = 0.319, P = 0.01). Moreover, PaO(2) (P = 0.02), P(A-a)O(2) (P = 0.005), and SpO(2) at the end of exercise (P = 0.023) were independent predictors of the presence of estimated PH. Using Doppler echocardiography as a screening tool for the estimation of PH, we found that PH is common in patients with IPF. Gas exchange parameters at rest and exercise desaturation might indicate underlying PH in IPF.

Topics: Aged; Echocardiography; Echocardiography, Doppler; Exercise Test; Familial Primary Pulmonary Hypertension; Female; Greece; Humans; Hypertension, Pulmonary; Idiopathic Pulmonary Fibrosis; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Prevalence; Prospective Studies; Respiratory Function Tests; Walking

Epidemiological studies support a hypothesis that pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) that is associated with a high risk of death and evolves as a complication of haemolytic anaemia. This fundamental hypothesis has been recently challenged and remains controversial. In order to further test this hypothesis in a large and independent cohort of SCD patients we obtained plasma samples from the Cooperative Study of Sickle Cell Disease (CSSCD) for analysis of a biomarker, N-terminal-pro brain natriuretic peptide (NT-proBNP), which is elevated in the setting of pulmonary arterial and venous hypertension. A NT-pro-BNP value previously identified to predict PH in adults with SCD was used to determine the association between the risk of mortality in 758 CSSCD participants (428 children and 330 adults). An abnormally high NT-proBNP level ≥160ng/l was present in 27·6% of adult SCD patients. High levels were associated with markers of haemolytic anaemia, such as low haemoglobin level (P<0·001), high lactate dehydrogenase (P<0·001), and high total bilirubin levels (P<0·007). A NT-proBNP level ≥160ng/l was an independent predictor of mortality (RR 6·24, 95% CI 2·9-13·3, P<0·0001). These findings provide further support for an association between haemolytic anaemia and cardiovascular complications in this patient population.

Topics: Adult; Age Distribution; Anemia, Hemolytic; Anemia, Sickle Cell; Biomarkers; Child; Child, Preschool; Epidemiologic Methods; Female; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; United States

Topics: Adult; Aged; Coronary Sinus; Echocardiography; Familial Primary Pulmonary Hypertension; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors

To compare [NT-proBNP], [NT-proANP] and [cTnI] between control dogs with respiratory disease without pulmonary hypertension (PH) and dogs with pre-capillary PH, and to assess the accuracy of [NT-proBNP], [NT-proANP], [cTnI] to predict Doppler-derived peak tricuspid regurgitation (TR) gradient.. 20 dogs. 8 control dogs with respiratory disease with no PH and 12 with pre-capillary PH.. [NT-proBNP], [NT-proANP] and [cTnI] were compared between the 2 groups and simple linear regression analysis was used to predict peak TR gradients from various blood biomarkers.. Median [NT-proBNP] was higher in the dogs with PH (2011 pmol/L, 274-7713 pmol/L) compared to control dogs (744 pmol/L; 531-2710 pmol/L) (p = 0.0339). [NT-proBNP] was associated with peak TR gradient (R(2) = 0.7851, p = 0.0001). Median [NT-proANP] did not differ between dogs with PH (1747 fmol/L; 894-2884 fmol/L) and control dogs (1209 fmol/L; 976-1389 fmol/L (p = 0.058). [NT-proANP] was not associated with peak TR gradient (R(2) = 0.2780, p = 0.0781). Median [cTnI] did not differ between dogs with PH (0.2850 ng/mL; 0.19-1.13 ng/mL) and control dogs (0.2 ng/mL; 0.19-0.82 ng/mL, p = 0.3051). Median [TnI] was not associated with peak TR gradient (R(2) = 0.024, p = 0.6307).. [NT-proBNP] concentration is significantly higher in dogs with pre-capillary PH when compared to dogs with respiratory disease without PH, and [NT-proBNP] may be useful to predict the severity of estimated PH. Elevations in [NT-proBNP] due to pre-capillary PH may complicate the interpretation of [NT-proBNP] elevations in patients presenting with cardiorespiratory abnormalities. [NT-proANP] and [cTnI] were not elevated in dogs with pre-capillary PH.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Dog Diseases; Dogs; Female; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Peptide Fragments; Troponin I

Previous studies have shown the prognostic benefit of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in pulmonary arterial hypertension (PAH) at time of diagnosis. However, there are only limited data on the clinical utility of serial measurements of the inactive peptide NT-pro-BNP in PAH. This study examined the value of serial NT-pro-BNP measurements in predicting prognosis PAH. We retrospectively analyzed all available NT-pro-BNP plasma samples in 198 patients who were diagnosed with World Health Organization group I PAH from January 2002 through January 2009. At time of diagnosis median NT-pro-BNP levels were significantly different between survivors (610 pg/ml, range 6 to 8,714) and nonsurvivors (2,609 pg/ml, range 28 to 9,828, p <0.001). In addition, NT-pro-BNP was significantly associated (p <0.001) with other parameters of disease severity (6-minute walking distance, functional class). Receiver operating curve analysis identified ≥1,256 pg/ml as the optimal NT-pro-BNP cutoff for predicting mortality at time of diagnosis. Serial measurements allowed calculation of baseline NT-pro-BNP (i.e., intercept obtained by back-extrapolation of concentration-time graph), providing a better discrimination between survivors and nonsurvivors than NT-pro-BNP at time of diagnosis alone (p = 0.010). Furthermore, a decrease of NT-pro-BNP of >15%/year was associated with survival. In conclusion, a serum NT-pro-BNP level ≥1,256 pg/ml at time of diagnosis identifies poor outcome in patients with PAH. In addition, a decrease in NT-pro-BNP of >15%/year is associated with survival in PAH.

Topics: Familial Primary Pulmonary Hypertension; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Protein Precursors; Retrospective Studies; ROC Curve; Severity of Illness Index

Vascular complications, including pulmonary hypertension (PH), have been reported to occur following splenectomy for various disorders,including hereditary spherocytosis (HS). We performed a prospective cross-sectional study of 36 adults with HS (78% with prior splenectomy)utilizing echocardiography to estimate tricuspid regurgitant jet velocity (TRV) as well as measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) to screen for PH. No participant with HS hada significantly elevated TRV or NT-proBNP level, despite a median 25-year interval since splenectomy (95% confidence interval for point prevalence 0, 0.097). Although our study was limited by a small sample size, it appears that persons with HS, following splenectomy, appear unlikely to be at significantly increased risk of developing PH to the degree reported for thalassemia and sickle cell disease

Topics: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Early Diagnosis; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Prevalence; Prospective Studies; Protein Precursors; Risk Factors; Spherocytosis, Hereditary; Splenectomy; Texas; Tricuspid Valve; Ultrasonography; Young Adult

Topics: Acute Coronary Syndrome; Americas; Atrial Natriuretic Factor; Biomarkers; Dyspnea; Early Diagnosis; Emergency Service, Hospital; Europe; Heart Diseases; Heart Failure; Humans; Hypertension, Pulmonary; Intensive Care Units; Japan; Myocardial Infarction; Natriuretic Peptide, Brain; Patient Discharge; Peptide Fragments; Practice Guidelines as Topic; Predictive Value of Tests; Prognosis; Survival Rate; Troponin; Ventricular Dysfunction, Left

The levels of C-reactive protein (CRP), tumor necrosis factor (TNF)-α, brain natriuretic peptide (BNP) and endothelin-1 (ET-1) were investigated to analyze the systemic inflammation in chronic obstructive pulmonary disease (COPD) patients with and without pulmonary hypertension.. From January 2006 to December 2010, 89 patients with COPD were enrolled in our hospital. There were 67 males and 22 females, with a mean age of (70 ± 7) and a mean FEV(1) of (47 ± 13)%. Pulmonary pressure was assessed by Doppler echocardiography. The levels of plasma BNP, TNF-α and ET-1 were measured by enzyme-linked immunosorbent assay kits. High-sensitivity plasma CRP level was assessed by chemiluminescent immunoassay.. Forty-two patients were classified as COPD with pulmonary hypertension group and 47 patients as COPD without pulmonary hypertension group. The level of CRP [51.4 mg/L (20.1 - 92.0) mg/L], ET-1 [5.9 ng/L (3.7 - 10.4) ng/L] and BNP [303.2 ng/L (112.5 - 824.7) ng/L] in patients with pulmonary hypertension were significantly higher than in that in patients without hypertension, CRP [26.7 mg/L (11.5 - 62.9) mg/L], ET-1 [2.1 ng/L (1.3 - 4.7) ng/L] and BNP [143.7 ng/L (85.5 - 306.7) ng/L]. The level of TNF-α showed no difference between the 2 groups [8.5 ng/L (4.8 - 13.7) ng/L and 6.7 ng/L (3.2 - 10.3) ng/L], respectively. Multivariate analysis showed that PaO₂ (P < 0.05), CRP (P < 0.05) and BNP (P < 0.05) could predict pulmonary hypertension independently.. The level of CRP, ET-1 and BNP were related to pulmonary hypertension in COPD patients, suggesting that systemic inflammation play a role in the pathogenesis of pulmonary hypertension in COPD.

Topics: Aged; C-Reactive Protein; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Inflammation; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha

To explore the relationship of spinal ventricular septal angle (SVSA) measured by computer tomographic pulmonary angiography (CTPA) and right cardiac functions, N-terminal brain natriuretic peptide (NT-proBNP) in the patients with chronic thromboembolic pulmonary hypertension (CTEPH).. Forty-four CTEPH patients, 26 males and 18 females aged (52 ± 12) years old on average, at our hospital from January 2008 to January 2010 were retrospectively reviewed. SVSA and such pulmonary artery obstruction indices as Qanadli and Mastora indices were evaluated by two independent radiologists. The parameters of right heart functions were evaluated by echocardiography and right-heart catheterization. The level of NT-proBNP was measured by enzyme linked immunosorbent assay (ELISA).. SVSA was (63 ± 11)° in CTEPH and (40 ± 7)° in the control group. The differences were significant (t = 12.320, P = 0.000). SVSA had a moderately positive correlation with the level of NT-proBNP (r = 0.704, P = 0.000). A positive correlation existed between SVSA and right atrium transverse diameter (r = 0.381, P = 0.002), right atrium long axis diameter (r = 0.437, P = 0.000) and right ventricular transverse diameter (r = 0.449, P = 0.000) on echocardiography. But there was no correlation between SVSA and right ventricular ejection fraction (r = -0.175, P = 0.365, n = 24). Also there was a negative correlation between SVSA and cardiac output (r = -0.337, P = 0.025), cardiac index (r = -0.351, P = 0.020), right cardiac work (r = -0.307, P = 0.043) and right ventricular stroke work (r = -0.384, P = 0.010).. Spinal ventricular septal angle measured on CTPA may serve as a better predictor for evaluating the level of NT-proBNP and right cardiac functions in CTEPH.

Topics: Adult; Aged; Aged, 80 and over; Angiography; Case-Control Studies; Female; Heart Ventricles; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Tomography, X-Ray Computed; Ventricular Function, Right; Ventricular Septum

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of neurohormonal activation that is useful in the diagnosis and prognosis of various forms of pulmonary arterial hypertension (PAH). We sought to characterise and compare NT-proBNP in a cohort of PAH related to systemic sclerosis (PAH-SSc) and idiopathic PAH (IPAH) patients. NT-proBNP levels, collected from PAH-SSc and IPAH patients followed prospectively, were compared and correlated with haemodynamic variables. Cox proportional hazard models were created to assess the predictive value of NT-proBNP. 98 patients (55 PAH-SSc, 43 IPAH) were included. Haemodynamics were similar, except for lower mean pulmonary arterial pressure in PAH-SSc. NT-proBNP levels were significantly higher in PAH-SSc (3,419+/-3,784 versus 1,393+/-1,633 pg x mL(-1); p<0.01) and were more closely related to haemodynamics in PAH-SSc than IPAH. 28 patients died. NT-proBNP predicted survival (hazard ratio (HR) 3.18; p<0.01) in the overall cohort; however, when stratified by group, predicted survival only in PAH-SSc (HR 3.07, p<0.01 versus 2.02, p = 0.29 in IPAH). This is the first description showing NT-proBNP levels are 1) significantly higher in PAH-SSc than IPAH despite less severe haemodynamic perturbations, and 2) stronger predictors of survival in PAH-SSc, suggesting that neurohormonal regulation may differ between PAH-SSc and IPAH. Future studies to define pertinent mechanisms are warranted.

Topics: Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Scleroderma, Systemic

Acute right ventricular failure in the setting of pulmonary arterial hypertension (PAH) often requires hospitalisation in intensive care units (ICU) to manage the subsequent low cardiac output and its consequences. There are very few data on these acute events. We recorded demographic, clinical and biological data and therapy in consecutive patients suffering from acute right heart failure requiring catecholamine treatment in the ICU of the French referral centre for pulmonary hypertension. These variables were analysed according to the survival status in ICU. 46 patients were included, the mean age was 50.3 yrs. ICU mortality was 41%. We found no difference in terms of demographics, clinical data, last haemodynamic measurements at admission. Systemic arterial pressure was significantly lower in the subgroup of patients whose clinical course was fatal. Plasma brain natriuretic peptide (BNP), C-reactive protein (CRP), serum sodium and creatinine at admission correlated with survival. Demonstration of an infection during the ICU stay was associated with a worse prognosis. These preliminary results underline the importance of some simple clinical and biological parameters in the prognostic evaluation of acute heart failure in the setting of PAH. Whether these parameters can guide therapy needs to be further investigated.

Topics: Acute Disease; Adolescent; Adult; Aged; Blood Pressure; C-Reactive Protein; Cardiotonic Agents; Creatinine; Dobutamine; Female; Heart Failure; Hospital Mortality; Humans; Hypertension, Pulmonary; Intensive Care Units; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Factors; Sodium; Survival Analysis; Vasoconstrictor Agents; Young Adult

The lungs of patients with pulmonary arterial hypertension (PAH) exhibit decreased bioavailability of nitric oxide and downstream signaling through cyclic guanosine monophosphate (cGMP). Therapies that enhance cGMP-mediated vasodilation have shown efficacy in treating PAH. We tested the hypothesis that combination therapy with sildenafil, a cGMP phosphodiesterase type 5 inhibitor, and brain natriuretic peptide (BNP), a receptor-mediated guanosine cyclase stimulator, synergistically attenuates monocrotaline-induced PAH in rats compared with either monotherapy.. Adult male Sprague-Dawley rats were subcutaneously injected with monocrotaline (n = 41, 50 mg/kg). After approximately 4 weeks, the rats were infused intravenously with vehicle solution, sildenafil (42 and 85 microg/kg/min), or BNP (50 and 100 ng/kg/min), alone and in varied combination. The primary endpoint was the relative change in right ventricular systolic pressure (RVSP) and mean arterial systemic pressure (MAP). Secondary endpoints included heart rate and dP/dt.. Vehicle infusions did not alter hemodynamic variables. Sildenafil85 (85 microg/kg/min) alone decreased RVSP (-16.6 +/- 5.6%) and decreased MAP (-4.0 +/- 4.7%). BNP50 (50 ng/kg/min) and BNP100 (100 ng/kg/min) decreased RVSP (-23.3 +/- 5.7% and -27.1 +/- 2.9%, respectively) and MAP (-6.4 +/- 5.8% and -14.3 +/- 4.1%, respectively). Combination therapy with sildenafil42 and BNP50 decreased RVSP (-20.7 +/- 5.6%) and showed a lessened systemic effect (MAP = -11.6 +/- 5.9%). Combination therapy with sildenafil85 and BNP100 decreased RVSP (-27.6 +/- 3.2%, P = NS) and showed increased systemic effect (MAP = -20.7 +/- 3.1%, P < 0.05) in comparison with sildenafil85.. This study suggests that intravenous administration of both sildenafil and BNP monotherapy produces significant improvement in RVSP, making them potentially viable options for the treatment of PAH, whereas combination therapy produces no additional improvement in pulmonary hemodynamics.

Topics: Animals; Drug Therapy, Combination; Hemodynamics; Hypertension, Pulmonary; Male; Monocrotaline; Natriuretic Peptide, Brain; Piperazines; Purines; Rats; Rats, Sprague-Dawley; Sildenafil Citrate; Sulfones; Time Factors

Topics: Biomarkers; C-Reactive Protein; Heart Diseases; Humans; Hypertension, Pulmonary; Inflammation; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Disease, Chronic Obstructive

The aim of this study was to determine the prevalence of pulmonary hypertension (PH) in sickle cell disease and thalassemia patients in relation to clinical and laboratory parameters of hemolysis and hemosidersosis, as well as plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP). The study also aimed to define the role of thromboembolic pulmonary artery (PA) obstruction in its etiology. Forty sickle cell disease and 30 thalassemia patients [15 beta-thalassemia major (beta-TM) and 15 beta-thalassemia intermedia (beta-TI)] were screened for PH defined as tricuspid regurgitant velocity (TRV) >2.5 m/sec and evaluated for PA obstruction using ventilation-perfusion lung scan (V/Q), together with measurement of their plasma levels of NT-pro-BNP. Patients were prospectively followed up for a mean of 18 +/- 6.1 months. The prevalence of PH was 37.5, 40.0 and 26.7% in sickle cell disease, beta-TI and beta-TM patients, respectively. Pulmonary hypertension patients were older, had longer disease duration, higher serum ferritin, serum lactate dehydrogenase (LDH) and NT-pro-BNP with lower hemoglobin (Hb) levels compared to patients without PH. N-terminal pro-BNP was positively correlated with duration of illness, TRV, LDH, serum ferritin, and negatively correlated with Hb levels. The strongest predictor for TRV was serum ferritin followed by the NT-pro-BNP level. Forty-six-point-seven percent of sickle cell disease patients with PH had either high or intermediate probability V/Q scan results compared to 10% of thalassemic patients with PH who had high probability V/Q scan results. Pulmonary hypertension is highly prevalent in young sickle cell disease and thalassemia patients, where elevated serum ferritin and NT-pro-BNP are the main indicators.

Topics: Adolescent; Adult; Anemia, Sickle Cell; beta-Thalassemia; Child; Chromatography, High Pressure Liquid; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Regression Analysis; Ventilation-Perfusion Ratio; Young Adult

To study the plasma natriuretic peptide (BNP) level in children with pulmonary artery hypertension (PAH) secondary to congenital heart disease (CHD) and its correlation with left ventricular diastolic function.. Doppler echocardiography was performed on 95 CHD children with PAH (PAH group) and on 42 CHD without PAH (control group). The plasma BNP level was measured using radioimmunity assay.. Doppler echocardiography showed that the left ventricular end-diastolic diameter (LVDd), the right ventricular diameter end-diastolic (RVDd), and the pulmonary artery diameter (PAd) increased significantly in the PAH group compared with those in the control group (p<0.05). The PAH group had higher velocity of tricuspid regurgitation (VTR) and higher pulmonary artery systolic pressure (PASP) than the control group (p<0.05). The PAH group also had higher mitral A peak velocity (AV), higher mitral A peak velocity integral (AVI), higher E peak velocity intgral (EVI), and higher ratio of mitral AV to mitral E peak velocity (EV) and AVI/EVI ratio as well as prolonged left ventricular volumetric relaxation time than the control group. PASP was positively correlated with the AV/EV ratio (p<0.05). The plasma BNP level in the PAH group increased significantly compared with that in the control group. In the PAH group, the plasma BNP level was positively correlated with the pulmonary artery pressure and the ratio of AV/EV.. The left ventricular diastolic function is positively correlated with the plasma BNP level in children with PAH secondary to CHD. BNP may play an important role in the generation and development of left ventricular diastolic dysfunction induced by PAH.

Topics: Child; Child, Preschool; Diastole; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Male; Natriuretic Peptide, Brain; Ventricular Function, Left

To describe the features of pulmonary arterial hypertension (PAH) in elderly patients.. A single centre, descriptive study of PAH patients consecutively referred to a regional centre, from September 2002 to February, 1st, 2009. The group of patients aged 65 and above at the time of the diagnosis was compared to the younger patients.. Sixty-six patients suffering from PAH (group 1) have been investigated by means of right heart catheterisation. There were 24 patients aged 65 and above. Mean pulmonary arterial pressure was lower in the patients aged over 65. The older patient group had more respiratory and/or cardiac co-morbidities, a lower median distance in the 6minute walk test and a higher median Pro-BNP level. Specific PAH treatments were prescribed in both groups. Fifteen patients aged 65 and above were on long-term oxygen therapy (vs four younger patients, p<0.0001). The elderly patients had a median survival of 32 months.. The diagnosis of PAH in elderly patients is associated with a poor prognosis. The management of these patients needs further studies.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Cardiac Catheterization; Cohort Studies; Comorbidity; Exercise Test; Female; France; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Wedge Pressure; Young Adult

Elevated pulmonary vascular resistance portends a poor prognosis across interstitial lung disease (ILD), irrespective of the histospecific diagnosis. Currently, no noninvasive surrogate prognostic marker exists. We explore the prognostic value of brain natriuretic peptide (BNP) and echocardiography across ILD. ILD patients with BNP concentrations performed during 2005-2007 were reviewed (n = 90). Echocardiography tapes were reviewed by a cardiologist blinded to other results. Outcome was evaluated for survival against BNP and echocardiograph parameters. A priori threshold values and composite markers were evaluated against survival. During follow-up (20±9 months) there were 28 deaths (31%). BNP correlated with right heart echocardiographic indices, including right ventricular systolic pressure (RVSP) (R(2) = 0.18, p = 0.0002) but not with parameters of left heart function. Nonsurvivors had higher BNP and RVSP levels than survivors. BNP ≥20 pmol·L(-1) (hazard ratio (HR) 2.93, 95% CI 1.28-6.73; p = 0.01) and moderate-severe pulmonary hypertension (HR 2.53, 95% CI 1.15-5.57; p = 0.02) were associated with increased mortality, independent of age, sex and pulmonary function. Patients with BNP ≥20 pmol·L(-1) had a 14-fold increased mortality over those with BNP <4 pmol·L(-1). Increased BNP levels and/or echocardiographic markers of right ventricular dysfunction were associated with increased mortality across ILD. The link between vascular parameters and mortality supports the concept that pulmonary vascular disease contributes to the final common pathway seen across ILD.

Topics: Aged; Echocardiography; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Regression Analysis; Treatment Outcome; Ventricular Dysfunction, Right

To identify factors related to NT-proBNP levels in systemic sclerosis (SSc).. NT-proBNP was measured in 119 patients with SSc and 20 controls. Patients with transtricuspid gradient (TG) > or =36 mm Hg or > or =31 mmHg plus dyspnea were considered to have suspected systemic sclerosis-associated pulmonary arterial hypertension (SScPAH).. Increasing age, NYHA functional class, skin score, history of systemic arterial hypertension (SAH), anticentromere antibodies, diastolic dysfunction, reduced pulmonary diffusing capacity, and TG were positively associated with NT-proBNP. In multivariable linear regression, TG, age, and SAH were independently associated to NT-proBNP levels. An ROC curve analysis (with an area under the curve of 0.89, 95% CI: 0.83-0.95) suggested a cutoff of 157.8pg/mL to identify patients with suspected SScPAH, presenting a sensitivity of 100% (78.1-100) and specificity of 72.3% (62.3-80.5).. NT-proBNP levels are related to clinical and laboratory abnormalities in SSc. The results indicate that NT-proBNP may be a useful tool in the evaluation of SScPAH.

Topics: Adult; Age Factors; Case-Control Studies; Female; Humans; Hypertension; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Scleroderma, Systemic; Sensitivity and Specificity; Triglycerides

Liver dysfunction reflects the status of heart failure, with congestion and low perfusion of the liver serving as causative mechanisms. Previous studies demonstrated relationship between the results of liver function test and the prognosis in patients with heart failure. However, few studies have examined this relationship in patients with pulmonary arterial hypertension (PAH).. The subjects were 37 patients with PAH (8 men and 29 women; 18 with idiopathic PAH and 19 with connective tissue disease-associated PAH). A blood test was performed after a 3-month period free from hospitalization and without changes in functional class, treatment, heart sounds, body weight, or heart rate.. In a mean follow-up period of 635 +/- 510 days, 12 patients died due to heart failure, 2 died due to pulmonary hemorrhage, and 23 patients survived. Cox proportional hazard analyses identified functional class (p < 0.001), plasma concentration of brain natriuretic peptide (BNP) (p = 0.001), and hyperbilirubinemia (serum total bilirubin > 1.2 mg/dL; p < 0.001; hazard ratio = 13.31) as predictors of mortality. Patients with hyperbilirubinemia had a worse functional class (P = 0.003), a higher right atrial pressure (p < 0.001), a higher plasma concentration of BNP (p = 0.004), and a larger Doppler right ventricular index of the right ventricle (p = 0.041).. Elevated serum bilirubin is a risk factor for death in patients with PAH.

Topics: Adult; Aged; Bilirubin; Biomarkers; Echocardiography, Doppler; Female; Heart Failure; Heart Ventricles; Humans; Hyperbilirubinemia; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Factors

Early detection of pulmonary hypertension (PH) in patients with systemic sclerosis (SSc) is essential as it leads to substantial morbidity and mortality irrespective of its etiology. The aim of our study was to determine whether noninvasive biochemical and/or echocardiographic indices can predict the presence of PH in these patients. We prospectively studied 66 patients (mean age of 57.7 +/- 12.1 years, 63 women) with SSc without clinical manifestations of heart failure. All patients underwent standard and tissue Doppler echocardiography. Plasma N-terminal pro-B type natriuretic peptide (NT-proBNP) and asymmetric dimethylarginine (ADMA) levels were also measured. In 24 (36%) patients, the diagnosis of PH was established by echocardiography (systolic pulmonary artery pressure value > or =40 mmHg). Left atrial (LA) volume, NT-proBNP, ADMA, ratio of early transmitral filling velocity to early diastolic velocity of the mitral annulus (mitral E/E (m)), and right ventricular myocardial performance index (MPI) were univariate predictors of PH. In multivariate analysis, NT-proBNP, LA volume, and right ventricular MPI were independent predictors of PH in SSc patients. LA volume and NT-proBNP may be useful noninvasive markers for the prediction of elevated pulmonary artery pressure in patients with SSc. These parameters should be considered when assessing this population for risk stratification and for identification of patients demanding further investigation and institution of specific therapy for the disease at the time when it is most likely to be effective.

Topics: Aged; Arginine; Biomarkers; Blood Pressure; Cross-Sectional Studies; Female; Follow-Up Studies; Heart Atria; Humans; Hypertension, Pulmonary; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Pulmonary Artery; Scleroderma, Systemic; Ultrasonography; Ventricular Dysfunction, Right

Besides persisting high pulmonary arterial pressure and increased pulmonary vascular resistance, remodelling of pulmonary tissues and subsequently the right heart are the key pathomechanisms of pulmonary hypertension (PH). Extracellular matrix maintenance in this context plays a central role.. We tested the hypothesis that plasma concentration of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinases (TIMP)-4 and tenascin C (TNC) might be useful as biomarkers for assessing the severity of PH. Therefore, the concentrations of MMP-2, TIMP-4, TNC and N-terminal b-type natriuretic peptide (NT-proBNP) of 36 PH patients were compared with those of 44 age- and gender-matched healthy volunteers. Additionally, lung function, 6-min walk distance and right heart function were assessed.. In PH patients, significantly elevated plasma levels of MMP-2, TIMP-4, TNC and NT-proBNP were detected. In particular, TIMP-4 was significantly increased in patients with higher NYHA classification, and in patients with severe right ventricular hypertrophy.. Monitoring of plasma TIMP-4 and to a lesser extent of MMP-2 and TNC levels in PH patients might help to assess the beneficial effects of PH pharmacotherapy on tissue remodelling.

Topics: Adult; Aged; Biomarkers; Cardiac Catheterization; Echocardiography; Exercise Test; Female; Humans; Hypertension, Pulmonary; Immunoassay; Lung; Male; Matrix Metalloproteinase 2; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Respiratory Function Tests; Tissue Inhibitor of Metalloproteinase-4; Tissue Inhibitor of Metalloproteinases; Tumor Necrosis Factors; Walking

To determine the diagnostic utility of circulating angiopoietin-1 (Ang-1) and its antagonist angiopoietin-2 (Ang-2) as potential biomarkers of disease severity or response to treatment in idiopathic pulmonary arterial hypertension (IPAH). Imbalances in angiogenic factors including vascular endothelial cell growth factor (VEGF) and the angiopoetin-Tie2 receptor system have been implicated in the pathogenesis of IPAH.. Plasma Ang-1, Ang-2, soluble Tie2 (sTie2), and VEGF were determined by in-house immunoassays in two cohorts of IPAH patients: a retrospective cohort (n = 81) and a prospective cohort (n = 25). Ten patients with normal pulmonary artery pressures and 14 apparently healthy subjects served as controls. Plasma levels of all angiogenic factors were elevated in IPAH patients compared with controls (all P < 0.005). Angiopoietin-2, but not Ang-1, sTie2, and VEGF correlated with cardiac index (r = -0.53, P < 0.001), pulmonary vascular resistance (PVR) (r= 0.60, P < 0.001), and mixed venous oxygen saturation (SvO(2)) (r= -0.63, P < 0.001). In multivariate analysis, elevated Ang-2 was an independent risk factor of mortality (P = 0.004). The patients in the prospective cohort were studied longitudinally at baseline and 3 months after initiation of therapy. Changes in Ang-2 after initiation of therapy correlated with changes in mean right atrial pressure (r = 0.6, P = 0.008), PVR (r = 0.51, P = 0.04), and inversely related to changes in SvO(2) (r = -0.75, P < 0.001). Histological studies showed that the expression of Ang-2 mRNA and protein was up-regulated in plexiform lesions from IPAH lung tissue samples.. Ang-2 may be involved in the pathogenesis of IPAH, and plasma Ang-2 might serve as a promising new biomarker of disease severity and response to treatment in patients with IPAH.

Topics: Adult; Angiopoietin-1; Angiopoietin-2; Biomarkers; Case-Control Studies; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Immunohistochemistry; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Retrospective Studies; Vascular Endothelial Growth Factor A

Pulmonary hypertension (PH) still remains a serious disease, for which the plasma level of brain natriuretic peptide (BNP) and hemodynamic variables (eg, cardiac index: CI) are established prognostic factors. The aim of the present study was to identify new additional prognostic factors of the disorder to improve the management of PH.. The study cohort comprised 136 consecutive PH patients admitted to hospital from 1974 to 2008, all of whom were closely followed every 6-12 months. During the follow-up period of 53.5+/-4.5 [SEM] months, 47 patients died of cardiopulmonary causes. The patients who were initially treated with monotherapy showed improved pulmonary hemodynamics when subsequently treated with combination therapy. Multivariate analysis showed that BNP and CI were significant and independent prognostic factors in all PH patients. However, in PH patients with low CI at diagnosis, only CI improvement by PH therapy was a significant and independent prognostic factor. Indeed, the patients with low CI at diagnosis (CI <2.5) followed by subsequent normalization in response to therapy (CI > or =2.5) showed a significantly better survival compared with those without such normalization.. CI normalization in response to treatment is an independent new prognostic factor of PH in patients with low CI at diagnosis, suggesting the importance of intensive therapy to achieve CI normalization.

Topics: Cohort Studies; Disease Management; Female; Follow-Up Studies; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis

To compare the performance of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc).. Between January 2008 and March 2009, outpatients referred to our unit and satisfying LeRoy criteria for SSc were assessed for PAH. Doppler echocardiography, BNP measurement, and NT-proBNP measurement were done concomitantly for a complete clinical, instrumental, and biochemical evaluation. Right-heart catheterization was carried out in cases of suspected PAH [estimated pulmonary arterial pressure (PAP) ≥ 36 mm Hg; diffusion capacity for carbon monoxide (DLCO) ≤ 50% of predicted value; 1-year DLCO decline ≥ 20% in absence of pulmonary fibrosis; unexplained dyspnea].. One hundred thirty-five patients were enrolled (124 women, 11 men; 96 limited SSc, 39 diffuse SSc); precapillary PAH was found in 20 patients (15 limited SSc, 5 diffuse SSc). The estimated PAP correlated with both BNP (R = 0.3; 95% CI 0.14-0.44) and NT-proBNP (R = 0.3, 95% CI 0.14-0.45). BNP [area under the curve (AUC) 0.74, 95% CI 0.59-0.89] was slightly superior to NT-proBNP (AUC 0.63, 95% CI 0.46-0.80) in identification of PAH, with diagnosis cutoff values of 64 pg/ml (sensitivity 60%, specificity 87%) and 239.4 pg/ml (sensitivity 45%, specificity 90%), respectively. BNP (log-transformed, p = 0.032) and creatinine (p = 0.049) were independent predictors of PAH, while NT-proBNP was not (p = 0.50).. In our single-center study, the performance of BNP was slightly superior to that of NT-proBNP in PAH screening of patients with SSc, although normal levels of these markers do not exclude diagnosis. We observed that impaired renal function is associated with an increased risk of PAH in SSc. Further multicenter studies are needed to confirm our results (ClinicalTrials.gov ID NCT00617487).

Topics: Adult; Aged; Area Under Curve; Biomarkers; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Scleroderma, Systemic; Sensitivity and Specificity

Topics: Adult; Anemia, Hemolytic, Congenital; Anemia, Sickle Cell; Animals; Biomarkers; Cardiac Catheterization; Clinical Trials as Topic; Disease Models, Animal; Humans; Hypertension, Pulmonary; Male; Mice; Natriuretic Peptide, Brain; Nitric Oxide; Peptide Fragments; Priapism; Risk Factors; Treatment Failure; Tricuspid Valve Insufficiency; Ultrasonography

Persistent pulmonary hypertension of the newborn (PPHN) is a major clinical problem. Nitric oxide produced by endothelial nitric oxide synthase (eNOS) in endothelial cells plays an important role in the pathogenesis of PPHN. The eNOS expression in endothelial cells is controlled by epigenetic regulation. The aim of this study was to investigate the epigenetic regulatory mechanisms of the eNOS gene in PPHN.. The rat model of PPHN was induced by hypoxia and indomethacin. Pulmonary vascular endothelial cells were isolated from the fetal rat lungs by magnetic-activated cell sorting. Chromatin immunoprecipitation and bisulfite sequencing methods were used to analyze epigenetic regulation.. The levels of acetylated histone H3 and acetylated histone H4 at the proximal promoter of the eNOS gene in pulmonary vascular endothelial cells from PPHN were significantly higher than those from the control group (P < 0.01, respectively). Total methylation percentage of the eNOS gene promoter in PPHN rat was slightly lower than that of control, but there was no statistically significant difference between the two groups (24.7 ± 2.0 vs. 27.3 ± 2.3%, P = 0.408). These changes of epigenetic modifications at the eNOS gene promoter were consistent with increased levels of eNOS mRNA and protein in PPHN.. The increased expression of eNOS in PPHN was associated with epigenetic regulation.

Topics: Animals; Animals, Newborn; CpG Islands; Disease Models, Animal; DNA Methylation; Endothelial Cells; Epigenesis, Genetic; Female; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type III; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA

Limited data suggest a benefit following sildenafil treatment in patients with pulmonary hypertension (PH) and interstitial lung disease (ILD). The role of sildenafil in the management of PH in ILD is not clear. We report our experience of ILD patients with PH after 6-month sildenafil therapy.. We reviewed 15 patients (mean age 55 ± 15 years; 8 men) with ILD (mean FVC 52.6 ± 15.4%) and PH (mean right ventricular systolic pressure 73.8 ± 17.8 mm Hg). Median brain natriuretic peptide: 37 (5-452) pmol/L; mean 6MWD: 156 ± 101 m.. Following 6-month treatment with sildenafil, brain natriuretic peptide levels were lower (n = 12, P = 0.03), 6MWD was higher (n = 6, P < 0.05), but no change in right ventricular systolic pressure (n = 11) was demonstrated.. Our observations suggest that sildenafil may be useful in the management of PH in ILD. Controlled trials are warranted before therapeutic recommendations can be made.

Topics: Cohort Studies; Exercise Test; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents; Walking

Right ventricular dysfunction (RVD) detected by computerized tomography (CT)/echocardiography or elevated biomarkers is associated with a poor prognosis for pulmonary embolism (PE). However, these prognostic factors have not previously been concomitantly elucidated in the same patient group.. This prospective study included 108 consecutive patients with normotensive PE confirmed by CT pulmonary angiography (CTPA). On admission, patient serum NT-proBNP and troponin T (Tn-T) levels were measured, and echocardiography was performed within 24 hours after diagnosis of PE. Receiver operating characteristic (ROC) analysis was performed to determine the optimal echocardiographic end-diastolic diameters of the right ventricle, the ratio of the right ventricle to left ventricle (RV/LV ratio) on CTPA, and NT-proBNP and Tn-T cut-off levels with regard to prognosis.. All-cause 30-day mortality was 13% and PE-related mortality was 5.6%. RVD was defined as a right/left ventricular dimension ratio≥1.1 on CTPA and RV>30 mm on echocardiography by ROC analysis. A cut-off level of NT-proBNP≤90 pmol/ml had a high positive predictive value of 98% for survival, whereas NT-proBNP>300 and Tn-T≥0.027 had a negative predictive value, for all-cause deaths, of 95% and 96%, respectively. PE mortality in patients with NT-proBNP>300 and Tn-T≥0.027 reached 64%. In univariable analysis, the combination of Tn-T≥0.027 ng/ml with a echocardiographic RVD were the most significant predictors of overall mortality and PE-related death [HR: 14 (95% CI: 4.6-42,) and HR: 37.6 (95% CI: 4.4-324)], respectively. In multivariable Cox's regression analysis, NT-proBNP>300 and Tn-T≥0.027 HR: 26.5 (95% CI: 4.1-169.9, p<0.001) were the best combination to predict all-cause of mortality.. The combination of NT-proBNP and Tn-T clearly appears to be a better risk stratification predictor than biomarkers plus RVD on CT/ echocardiography in patients with normotensive PE.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Echocardiography; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Pulmonary Embolism; Risk Factors; Tomography, X-Ray Computed; Troponin I; Ventricular Dysfunction, Right; Young Adult

Recent advances in the treatment of pulmonary arterial hypertension provide a rational basis for earlier, noninvasive diagnosis of pulmonary arterial hypertension. However, the reliability of transthoracic echocardiography, plasma BNP levels, and other parameters for the diagnosis of pulmonary arterial hypertension remains unclear. Thus, the purpose of this study was to determine the utility of these modes of investigation for the prediction of pulmonary arterial pressure as compared with the current gold standard, Swan-Ganz catheterization. Among 46 PAH patients, 37 had connective tissue diseases, while the remainder had primary pulmonary arterial hypertension, chronic pulmonary thromboembolism, and interstitial pneumonitis. Systolic pulmonary arterial pressure calculated by transthoracic echocardiography was significantly correlated with systolic pulmonary arterial pressure measured using a Swan-Ganz catheter (r = 0.51, P < 0.01). Plasma BNP concentration did not correlate with systolic pulmonary arterial pressure (r = 0.10, NS) in the overall patient population. However, when we excluded left ventricular heart failure and left ventricular hypertrophy, BNP concentration was correlated with systolic pulmonary arterial pressure (r = 0.508, P < 0.05). Among other variables tested, ECG electrical axis was correlated with pulmonary arterial pressure (r = 0.46, P < 0.05) but uric acid, lactate dehydrogenase, %DLCO, enhanced IIp sound, and pulmonary artery enlargement on chest x-ray did not correlate with pulmonary arterial pressure. These data suggest that echocardiography is the noninvasive modality of choice for the assessment of pulmonary arterial hypertension. Plasma BNP level also predicts pulmonary arterial pressure, when left ventricular heart failure and cardiac hypertrophy are excluded.

Topics: Aged; Catheterization, Swan-Ganz; Connective Tissue Diseases; Electrocardiography; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Pulmonary Embolism; Retrospective Studies; Ultrasonography

Topics: Atrial Fibrillation; Echocardiography, Transesophageal; Exercise Test; Humans; Hypertension, Pulmonary; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Treatment Outcome; Ventricular Dysfunction, Left

Cardiac involvement and pulmonary hypertension (PH) are life-threatening complications in sarcoidosis.. This study aimed to investigate the utility of plasma NT-proBNP in the assessment of these conditions in sarcoidosis patients.. A prospective, observational study was performed on 150 consecutive Japanese sarcoidosis patients. Doppler echocardiography was performed in all subjects, and those who were successfully evaluated for PH status were included in the analysis. Cardiac sarcoidosis was diagnosed based on Japanese guidelines, and PH was defined as estimated systolic pulmonary artery pressure (sPAP) > or = 35 mmHg. The diagnostic accuracy of NT-proBNP according to the presence of cardiac sarcoidosis and PH was assessed based on receiver-operator characteristic (ROC) curves.. 130 subjects were successfully evaluated for PH status. Of these, 29 met the diagnostic criteria of cardiac sarcoidosis, and 21 were diagnosed with PH. Plasma NT-proBNP levels were significantly higher in patients with cardiac sarcoidosis (p < 0.0001). Stepwise regression analysis showed that presence of cardiac sarcoidosis, decreased ejection fraction and increased sPAP were all independently associated with higher plasma NT-proBNP levels. Plasma NT-proBNP showed good accuracy in identifying patients with cardiac sarcoidosis (area under the ROC curve; AURC = 0.913). However, even when patients with cardiac sarcoidosis were excluded, plasma NT-proBNP levels could not be used reliably to identify patients with PH (AURC = 0.681).. In patients with sarcoidosis, plasma NT-proBNP levels are a useful biomarker to identify cardiac involvement, but not to identify PH.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Cardiomyopathies; Chi-Square Distribution; Echocardiography, Doppler; Female; Humans; Hypertension, Pulmonary; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Pulmonary Artery; Regression Analysis; ROC Curve; Sarcoidosis; Stroke Volume; Up-Regulation

Chronic thromboembolic pulmonary hypertension is a disease affecting approximately 4,000 people per year in the United States. The incidence rate in Brazil, however, is unknown. The estimated survival for patients with chronic thromboembolic pulmonary hypertension without treatment is approximately three years. Pulmonary thromboendarterectomy for select patients is a potentially curative procedure when correctly applied. In Brazil, the clinical and hemodynamic profiles of chronic thromboembolic pulmonary hypertension patients have yet to be described.. To evaluate the clinical and hemodynamic characteristics of chronic thromboembolic pulmonary hypertension patients scheduled for pulmonary thromboendarterectomy in a referral center for chronic thromboembolic pulmonary hypertension treatment in Brazil.. From December 2006 to November 2009, patients were evaluated and scheduled for pulmonary thromboendarterectomy. The subjects were classified according to gender, age and functional class and were tested for thrombofilia and brain natriuretic peptide levels.. Thirty-five consecutive chronic thromboembolic pulmonary hypertension patients were evaluated. Two patients tested positive for schistosomiasis, and 31 were enrolled in the study (19 female, 12 male). The majority of patients were categorized in functional classes III and IV. Hemodynamic data showed a mean pulmonary vascular resistance (PVR) of 970.8 ± 494.36 dynas·s·cm-5 and a low cardiac output of 3.378 ± 1.13 L/min. Linear regression revealed a direct relation between cardiac output and pulmonary vascular resistance. Paradoxical septal movement was strongly correlated with pulmonary vascular resistance and cardiac output (p=0.001). Brain natriuretic peptide serum levels were elevated in 19 of 27 patients.. In a referral center for pulmonary hypertension in Brazil, chronic thromboembolic pulmonary hypertension patients evaluated for pulmonary thromboendarterectomy had a hemodynamically severe status and had elevated brain natriuretic peptide serum levels. There was a predominance of females in our cohort, and the prevalence of hematological disorders and schistosomiasis was low (less than 10%).

Topics: Adult; Brazil; Cardiac Output, Low; Chronic Disease; Endarterectomy; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Embolism; Schistosomiasis; Sex Distribution; Sex Factors; Vascular Resistance

We tried L-arginine for the treatment of pulmonary hypertension secondary to pulmonary embolism. The plasma brain natriuretic peptide (BNP) level inversely correlated with the plasma concentration of L-arginine. After oral supplementation of L-arginine, patient's symptoms (shortness of breath and general malaise), state of congestive heart failure, and exercise capacity all improved. L-arginine may be effective in the treatment of pulmonary hypertension secondary to pulmonary embolism.

Topics: Administration, Oral; Arginine; Dietary Supplements; Female; Heart Failure; Humans; Hypertension, Pulmonary; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Embolism

We aimed to assess whether levels of B-type natriuretic peptide (BNP)--an established marker of ventricular dysfunction--relate to functional status and outcome in children with idiopathic and associated pulmonary hypertension (PH).. BNP was measured in 50 children with PHT aged 8.4 +/- 5.1 years, all receiving PH specific therapies. Twenty-seven patients were diagnosed with idiopathic PH (IPAH), while 23 patients had associated PH [congenital heart disease (n = 17), lung disease (n = 4), other (n = 2)]. Functional status, six-minute walk test, echocardiographic and haemodynamic data were assessed. Mean BNP value was 143.5 +/- 236.2 pg/ml (range <5-1250). BNP correlated with Functional Class II, III, and IV (50.8 +/- 61.3, 196.9 +/- 291.2 and 280.0 +/- 276.5 respectively; p = 0.01), with echocardiographic assessment of right ventricular function (p < 0.01), hypertrophy (p < 0.01) and dilatation (p < 0.01). In IPAH BNP correlated with pulmonary arterial pressure and, on inhaled nitric oxide also with vascular resistance. During a mean follow-up of 14.0 +/- 7.5 months seven patients died, five underwent transplantation and two were listed for transplantation. Using ROC analysis, a BNP value >130 pg/ml predicted death or need for transplantation (p < 0.04). However, six children who died or were transplanted had a BNP value lower than this.. BNP correlated positively with functional status in children with pulmonary hypertension, but had limited sensitivity (57%) for predicting death or need for transplantation.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Female; Humans; Hypertension, Pulmonary; Infant; Kaplan-Meier Estimate; Lung Transplantation; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; ROC Curve; Sensitivity and Specificity

Topics: Antihypertensive Agents; Bosentan; Humans; Hypertension, Pulmonary; Models, Biological; Natriuretic Peptide, Brain; Peptide Fragments; Scleroderma, Systemic; Sulfonamides

Pulmonary arterial hypertension (PAH) is an important determinant of morbidity and mortality in children. In this study, we aimed to investigate the value of brain natriuretic peptide (BNP) in a cohort of children with PAH, with respect to monitoring disease severity as assessed by hemodynamic and echocardiographic parameters.. We performed a prospective study to determine whether BNP varies over time in this population and whether these changes track with hemodynamic or echocardiographic parameters. The population included a group of 78 pediatric patients from January 2005 to April 2008. All patients had received a diagnosis of PAH and had serum BNP, catheterization, and echocardiographic variables collected longitudinally.. The median BNP level, for all observations, was 36 pg/mL (interquartile range, 18 to 76 pg/mL). There was no strong correlation found between commonly used echocardiographic or hemodynamic data and BNP. However, using a bivariate model, the change in BNP measurements over time significantly correlated with the change in the hemodynamic and echocardiographic parameters. Patients with a BNP value > 180 pg/mL had a decreased survival rate.. BNP could be a useful marker to monitor disease severity in pediatric PAH. We show that simple correlations between variables and BNP are not likely to illustrate its usefulness due to variations in the normative levels. Instead, we propose that patient BNP levels should be monitored over time, as changes in BNP within a patient are likely to be more informative.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Echocardiography; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Infant; Male; Natriuretic Peptide, Brain; Prognosis; Survival Rate

Pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) is associated with poor prognosis. Recently echocardiography and brain natriuretic peptide (BNP) have been used as non-invasive markers for PH suggesting that they may also be used as markers for survival. The aim of this study was to evaluate the clinical usefulness of echocardiography and BNP by analyzing their association with survival.. Retrospective review of 131 patients with IPF who underwent both echocardiography and BNP measurement at a tertiary referral center.. Mean follow-up period was 10.1 months. Using systolic pulmonary arterial pressure of 40 mmHg as a threshold for PH, patients with PH had poor survival (1-year mortality rate: 61.2%, mean survival: 10.8 months) than those without PH (19.9%, 23.7 months; p<0.001). The prognosis of the subjects with increased BNP levels was poorer than those with normal BNP levels (1-year mortality rate: 70.5% vs. 23.7%, mean survival: 11.0 months vs. 22.5 months; p<0.001) and on multivariate analysis, only BNP level was an independent predictor of prognosis. On serial evaluation, the survival of patients with newly developed PH and/or elevated BNP levels was similar to that of patients with PH at the initial measurement, suggesting that development of PH is indicative of poor prognosis regardless of the timing of the test.. Although both BNP level and PH by echocardiography are clinically useful non-invasive and easily repeatable markers of prognosis, BNP level seems to be better.

Topics: Aged; Biomarkers; Echocardiography; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Idiopathic Pulmonary Fibrosis; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Severity of Illness Index; Survival Analysis

Primary pulmonary hypertension is a fatal disease that frequently becomes evident in pregnancy. The management of pregnant women with primary pulmonary hypertension poses a number of difficult problems, especially where regional anesthesia is considered to be contraindicated. A 30-year-old woman who developed primary pulmonary hypertension at 23 weeks of pregnancy was transferred to our hospital. Systolic pulmonary artery pressure and plasma brain natriuretic peptide levels were markedly elevated. Nitric oxide inhalation and prostacyclin prevented the progression of cardiac failure and reduced both plasma brain natriuretic peptide and pulmonary artery pressure. Cesarean section was performed at 32 weeks under general anesthesia. A combination of nitric oxide, prostacyclin, nitroglycerin, and dobutamine were administered during surgery. Intravenous dexmedetomidine was specifically used during emergence and recovery from anesthesia. This provided effective pain relief and hemodynamic stability. Throughout the clinical course, brain natriuretic peptide levels was monitored and used as an indicator of cardiac failure.

Topics: Adrenergic alpha-Agonists; Adult; Anesthesia, Obstetrical; Cesarean Section; Dexmedetomidine; Female; Heart Failure; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Pregnancy; Pregnancy Complications, Cardiovascular; Treatment Outcome

Pulmonary arterial hypertension (PAH) is a rare complication of glycogen storage disease (GSD), and several cases with a poor outcome have been reported. A 17-year-old boy, who was diagnosed with GSD at 1 year of age, complained of shortness of breath on exertion, and was diagnosed with PAH based on the echocardiographic findings. Beraprost sodium (BPS) was started, and his symptoms improved after 3 months of treatment. Eighteen months later, he experienced frequent episodes of syncope. Because increasing the dose of BPS was ineffective, he was admitted to hospital. The echocardiogram showed marked elevation of the right ventricular pressure and low cardiac output, and his symptoms deteriorated despite continuous infusion of olprinone hydrochloride. Because a single dose of sildenafil increased his cardiac output, treatment with 25 mg sildenafil twice daily was started. His symptoms gradually ameliorated, and 3 weeks later he left the hospital. Two months after starting sildenafil, the cardiac index and the serous B-type natriuretic peptide concentration had become normal. Sildenafil may be effective in patients with secondary PAH and in patients who have developed tolerance to BPS.

Topics: Administration, Oral; Adolescent; Antihypertensive Agents; Drug Tolerance; Echocardiography; Electrocardiography; Epoprostenol; Glycogen Storage Disease Type I; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Piperazines; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfones; Syncope; Treatment Outcome; Vasodilator Agents

Chronic thromboembolic pulmonary hypertension (CTPH) is a potential complication of pulmonary embolism (PE). Only few studies have assessed the role of brain natriuretic peptide (BNP) in patients with chronic pulmonary hypertension, and there are no data on the potential utility of BNP as a preclinical biomarker of CTPH. To assess the correlation between pulmonary artery systolic pressures (PAPs) and amino terminal proBNP (Nt-proBNP) and its value in the diagnosis of CTPH in patients with previous PE. Patients were evaluated with echocardiography at least 6 months after the index event. Pulmonary hypertension was defined as PAPs > or =40 mmHg at rest. Each subject underwent measurement of Nt-proBNP. Forty-nine patients were enrolled (mean age 64.5 +/- 13.1 years; 22 men). Seven patients had CTPH, and two were symptomatic. There was a good correlation between PAP on echocardiography and Nt-proBNP (r 0.64; P = 0.00003). Nt-proBNP was elevated in 6 of 7 patients [sensitivity: 85.7%; 95% confidence interval (CI): 48.7, 97.4] and it was normal in 35 of 42 patients without CTPH (specificity: 76.2%; 95% CI: 61.5, 86.5%). Six of the 13 patients with high Nt-proBNP levels had CTPH, whereas 1 of 36 patients with normal Nt-proBNP levels had pulmonary hypertension. The resulting positive predictive value was 46.1% (95% CI: 19.2, 74.9), and the negative predictive value was 97.2% (95% CI: 85.5-99.9). In conclusion, Nt-proBNP correlates with PAPs and may be used to exclude preclinical or symptomatic CTPH in patients with previous PE. Prospective studies on a larger population are warranted to confirm our preliminary findings.

Topics: Aged; Biomarkers; Chronic Disease; Female; Humans; Hypertension, Pulmonary; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism

Early diagnosis of chronic obstructive pulmonary disease (COPD) with latent pulmonary hypertension (PH) and cor pulmonale is important because the prognosis of this condition is poor.. To investigate the utility of brain natriuretic peptide (BNP) for prognostication of COPD, plasma BNP was measured in patients with COPD without symptoms or physical findings of PH or cor pulmonale.. Plasma BNP was measured in 60 patients with COPD, 10 asthmatics, and 30 healthy subjects. Echocardiography, arterial blood gas analysis, and spirometry were also performed. Mortality and exacerbation were compared between COPD patients with high and low plasma BNP levels over a 3-year follow-up period.. Plasma BNP (mean +/- SEM, pg/mL) in COPD patients (41.0+/-6.6) was significantly higher than in normal subjects (14.8+/-2.7) and asthmatics (17.4+/-4.5) (p<0.0001 and p<0.05, respectively). No significant correlations were observed between plasma BNP level and pulmonary function or hypoxia. There was, however, a significant correlation between plasma BNP level and % ejection fraction (r=-0.41, p=0.0197) and pulmonary artery systolic pressure (r=0.5, p=0.004). The period until initial COPD exacerbation in subjects with a high plasma BNP level was significantly shorter (p<0.05). Plasma BNP level during exacerbations (79.9+/-16.2) was also significantly higher than during stable disease (41.2+/-8.7) (p=0.004).. We suggest that plasma BNP is a non-invasive biomarker that can be used as a screening parameter for latent PH and left ventricular dysfunction, and also as a predictor of exacerbation in stable COPD.

Topics: Adult; Aged; Asthma; Biomarkers; Bronchodilator Agents; Carbon Dioxide; Case-Control Studies; Disease Progression; Echocardiography; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulmonary Heart Disease; Smoking; Spirometry; Stroke Volume

The aim of this study was to assessed the correlation of N-terminal natriuretic peptide type B (NT-proBNP) with echocardiographic and hemodynamic indexes of right ventricular (RV) function and to evaluate the sensitivity and specificity of Doppler echocardiography in the diagnosis of portopulmonary hypertension.. All patients underwent liver transplantation for cirrhosis. We obtained clinical data, NT-proBNP levels, echocardiography, and right heart hemodynamic measurements before transplantation.. Patients with pulmonary hypertension displayed significantly higher levels of NT-proBNP. They also showed higher model for End-stage Liver Disease scores and higher indices of RV overload on cardiac hemodynamics. The negative predictive value of echocardiography to identify pulmonary hypertension was 83%. A correlation was not observed between systolic pulmonary artery pressures measured by the two methods; however, NTproBNP showed a trend toward a significant correlation with mean pulmonary pressure as determined by hemodynamics (r = .3; P < .01).. We concluded that NT-proBNP values showed significant correlations with pulmonary hypertension that could assist in a noninvasive diagnoseis for this group of patients.

Topics: Biomarkers; Blood Pressure; Cardiac Catheterization; Cardiac Output; Electrocardiography; Hemodynamics; Humans; Hypertension, Pulmonary; Liver Cirrhosis; Liver Transplantation; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Wedge Pressure; Ventricular Dysfunction, Right

To study a plasmic concentration of the brain natriuretic peptide (BNUP) in patients with interstitial pulmonary disease (IPD) as a possible diagnostic parameter in pulmonary hypertension (PH).. Plasmic BNUP concentration, external respiration function were studied in 24 patients with IPD. The following tests were also made: 6-min walk, echocardiography (echo-CG) with estimation of systolic pressure in the pulmonary artery, multislice computed tomography of the chest with measurement of the mean diameter of the pulmonary artery trunk.. As shown by echo-CG and chest MSCT half of the IPD patients had PH. IPD patients with PH had a significant elevation of plasmic BNUP concentration which, in intact left ventricular contractile function indicates development of secondary PH characterized by reduction of volume parameters of the respiratory pulmonary function. The rise of BNUP concentration correlated with reduction of 6-min walk distance and functional lung capacity.. Plasmic BNUP can be used for diagnosis of PH in IPD patients.

Topics: Blood Pressure; Echocardiography; Exercise Test; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Artery

Topics: Chronic Disease; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Pulmonary Embolism

Right ventricular function affects the outcome in valvular heart disease but less is known about the relation between indices of dysfunction and outcome. Seventy patients undergoing mitral valve replacement between April 2007 and April 2008 for predominant rheumatic mitral stenosis were included in the study. Two groups were formed based on right ventricular systolic pressure (RVSP), 41 mmHg (group II, n=54). Right ventricle (RV) function indices were studied by echocardiography. RVSP reduced significantly in group II (P=0.0001) but not in group I. Brain natriuretic peptide (BNP) was raised in all cases and reduced significantly postoperatively. Tricuspid annular plane excursion, myocardial performance index, RV descent and tricuspid valve annular shortening (TV shortening) conformed to RV dysfunction in both groups, and did not change significantly postoperatively. Regression analysis for outcome revealed TV shortening as the only significant factor (P=0.03). Receiver operating characteristic of TV shortening and adverse outcome showed worse outcome with TV shortening of <11%. RV dysfunction was observed in all cases irrespective of RVSP. TV shortening of <11% was associated with adverse outcome. Postoperative fall in BNP levels may indicate a trend towards recovery.

Topics: Adult; Biomarkers; Female; Heart Valve Prosthesis Implantation; Humans; Hypertension, Pulmonary; Logistic Models; Male; Middle Aged; Mitral Valve Stenosis; Myocardial Contraction; Natriuretic Peptide, Brain; Peptide Fragments; Recovery of Function; Rheumatic Heart Disease; ROC Curve; Time Factors; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Pressure; Young Adult

Topics: Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Protein Precursors; Pulmonary Embolism

Red blood cell distribution width (RDW), a widely available biomarker, independently predicts adverse outcomes in left-sided heart failure. The relation between RDW and death in pulmonary hypertension (PH) is unknown. In a prospective study of 162 consecutive patients with PH, RDW was recorded during initial diagnostic right-sided cardiac catheterization, and patients were followed for 2.1 +/- 0.8 years to determine vital status. Demographic, clinical, laboratory, and hemodynamic variables were compared by tertile of RDW. Cox proportional-hazards models were used to determine whether RDW was independently associated with death, and the prognostic utility of RDW was compared to that of other laboratory predictors, including N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP). Of the 162 study patients, 78% were women, and 62% had pulmonary arterial hypertension. The mean age was 53 +/- 15 years, and most patients had severe PH (mean pulmonary artery pressure 48 +/- 13 mm Hg). The highest tertile of RDW predicted death (univariate hazard ratio 4.86, 95% confidence interval 1.37 to 17.29, p = 0.015; multivariate hazard ratio 2.4, 95% confidence interval 1.02 to 5.84, p = 0.045, after adjusting for age, gender, diabetes mellitus, connective tissue disease, diuretic use, phosphodiesterase inhibitor use, hemoglobin, mean corpuscular volume, and blood urea nitrogen [BUN]). Of the laboratory data, only RDW, BUN, and NT-pro-BNP were associated with death on univariate analysis. When RDW, BUN, and NT-pro-BNP were entered into a multivariate model, only RDW was still associated with death (p = 0.037 for RDW, p = 0.18 for BUN, and p = 0.39 for NT-pro-BNP). Adding NT-pro-BNP to RDW did not improve the prediction of mortality. In conclusion, RDW is independently associated with death in patients with PH and performs better as a prognostic indicator than NT-pro-BNP.

Topics: Adult; Aged; Erythrocyte Indices; Female; Humans; Hypertension, Pulmonary; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies

The POEMS syndrome is a rare plasma cell disease. Pulmonary hypertension is an infrequent respiratory complication of this syndrome and might be associated with increased levels of various cytokines, chemokines and growth factors as part of the inflammatory phenomena that involve the physiopathology of POEMS syndrome. We present the case of a 54-year-old woman diagnosed with POEMS syndrome and pulmonary hypertension, which were treated with corticosteroids as the first-line therapy. The patient presented with the classic symptoms of this syndrome: polyneuropathy (confirmed by electromyography), organomegaly, subclinical hypothyroidism and monoclonal gammopathy detected in urine, together with skin changes. Right heart catheterization revealed a mean pulmonary artery pressure of 48 mmHg, a cardiac output of 4.1 L/min and pulmonary vascular resistance of 8.05 Woods. The serum level of brain natriuretic peptide (BNP) was 150 pg/mL. No other underlying disease was found during the investigation. Prednisone (1 mg/kg for three months) was then initiated, with a dramatic improvement in the clinical and functional condition. Levels of thyroid hormones and urinary protein levels (as determined using electrophoresis) normalized. Mean pulmonary artery pressure decreased to 26 mmHg, cardiac output decreased to 3.8 L/min, and pulmonary vascular resistance decreased to 2.89 Woods. Serum levels of BNP dropped to 8 pg/mL. Our findings suggest that corticosteroids could play a role as a first-line treatment in pulmonary hypertension accompanied by POEMS syndrome. Due to the rarity of this presentation, a multicenter registry should be developed to allow the compilation of additional data to support this practice.

Topics: Adrenal Cortex Hormones; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Middle Aged; Natriuretic Peptide, Brain; POEMS Syndrome; Prednisone

To study the plasma concentration of brain natriuretic peptide (BNP) and endothelin-1 (ET-1) as markers of pulmonary hypertension (PH) developed in interstitial lung diseases (ILD).. Along with physical examination, 97 patients with ILD underwent measurements of the plasma concentrations of BNP and ET-1, 6-minute walk test, external respiration function test, echocardiography, by measuring pulmonary artery systolic pressure (P(syst)), and chest multispiral computed tomography, by estimating the mean diameter of the pulmonary artery trunk.. The plasma concentration of ET-1 proved to be significantly higher in the presence of active lung lesion (5.2 +/- 3.9 and 2.8 +/- 1.8 pg/ml; p = 0.0001). In patients with ILD, persistent PH was associated with the significantly elevated plasma concentrations of BNP (69.3 +/- 341.35 and 23.7 +/- 26.69 pg/ml; p = 0.018). The increase of plasma BNP concentrations correlated with the shorter distance covered during a 6-minute walk test and diminished functional vital capacity.. The increased plasma levels of ET-1 in ILD reflects the transient pulmonary artery pressure elevation associated with the activity of the pulmonary process while those of BNP are indicative of developed persistent PH.

Topics: Biomarkers; Case-Control Studies; Data Interpretation, Statistical; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Severity of Illness Index

Impaired endothelial homeostasis underlies the pathophysiology of pulmonary arterial hypertension (PAH). We speculated that PAH patients are deficient in circulating endothelial progenitor cells (EPCs), potentially contributing to endothelial dysfunction and disease progression.. We recruited 41 patients with Eisenmenger syndrome (13 with Down syndrome), 55 with idiopathic PAH, and 47 healthy control subjects. Flow cytometry and in vitro assays were used to quantify EPCs and to assess cell function. The number of circulating CD34+, CD34+/AC133+, CD34+/KDR+, and CD34+/AC133+/KDR+ progenitor cells was low in Eisenmenger patients compared with healthy control subjects, and those with Down syndrome displayed even fewer EPCs. Reductions in EPC numbers correlated with New York Heart Association functional class, 6-minute walk distance, and plasma brain-type natriuretic peptide levels. The capacity of cultured peripheral blood mononuclear cells to form colonies and incorporate into tube-like structures was impaired in Eisenmenger patients. Idiopathic PAH patients had reduced numbers of EPCs, and the number of circulating EPCs correlated with invasive hemodynamic parameters in this cohort. Levels of immune inflammatory markers, cGMP, stable nitric oxide oxidation products, and asymmetric dimethylarginine were abnormal in patients with PAH and related to numbers of EPCs. Within the idiopathic PAH population, treatment with the phosphodiesterase inhibitor sildenafil was associated with a dose-dependent rise in EPC numbers, resulting in levels consistently above those found with other therapies.. Circulating EPC numbers are reduced in 2 well-characterized forms of PAH, which also exhibit raised levels of inflammatory mediators. Sildenafil treatment may represent a pharmacological means of increasing circulating EPC numbers long-term.

Topics: AC133 Antigen; Aged; Antigens, CD; Antigens, CD34; Arginine; Cells, Cultured; Cyclic GMP; Down Syndrome; Eisenmenger Complex; Endothelium, Vascular; Exercise; Female; Flow Cytometry; Glycoproteins; Hematopoietic Stem Cells; Humans; Hypertension, Pulmonary; Inflammation Mediators; Male; Middle Aged; Natriuretic Peptide, Brain; Peptides; Piperazines; Pulmonary Artery; Purines; Sildenafil Citrate; Stem Cells; Sulfones; Vascular Endothelial Growth Factor Receptor-2; Vasodilator Agents

Topics: Biomarkers; Cohort Studies; Female; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Peptide Fragments; Scleroderma, Systemic

Pulmonary arterial hypertension (PAH) is a complication of scleroderma (systemic sclerosis, SSc); as soon as PAH develops, the patient's prognosis deteriorates rapidly. Early detection of PAH ensures timely treatment. We investigated the prevalence of exercise-induced PAH in a cohort of patients with SSc, and examined the relation between exercise-induced PAH and clinical characteristics and biochemical markers.. Patients with SSc and normal resting systolic pulmonary arterial pressure (sPAP) were studied. Eligible patients were asked to perform cycloergometer exercise until exhaustion, and exercise sPAP was measured. All patients had their pulmonary function tested and underwent echocardiography at rest. Brain natriuretic peptide (BNP) was also determined.. Forty-one patients with SSc were studied. Mean sPAP at rest was 29.7 mm Hg, rising to a mean of 41.4 mm Hg on exercise. Eleven of 41 patients (26.8%) had sPAP post-exercise > 50 mm Hg and 8/41 (19.5%) > 55 mm Hg. A significant correlation was found between exercise sPAP and DLCO (p = 0.008) and between sPAP and BNP levels (p = 0.04). Pre-existing severe Raynaud's phenomenon was more prevalent (50% vs 20%), DLCO levels lower (78.9 vs 92.7 % predicted), and BNP levels higher (72.6 vs 42.1 pmol/ml) in patients with exercise sPAP > 55 mm Hg.. The prevalence of exercise-induced PAH in patients with scleroderma is high. Patients with lower DLCO and higher levels of BNP are at higher risk of developing higher sPAP. Studies with longterm followup are required to evaluate the risk of developing resting PAH in these patients.

Topics: Blood Pressure Determination; Cross-Sectional Studies; Disease Progression; Echocardiography, Doppler; Exercise; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prevalence; Respiratory Function Tests; Scleroderma, Systemic; Spain

Pulmonary hypertension (PHT) has been reported to be high among end-stage renal disease (ESRD) patients. This study evaluated PHT in ESRD patients and the role of arteriovenous fistula (AVF), thromboxane B(2) (TXB(2)) and pro-BNP in this complication.. 45 ESRD patients on regular hemodialysis (HD) (group 1) and 31 ESRD patients on conservative treatment (group 2) underwent clinical and biochemical testing. Pulmonary artery pressure (PAP) was evaluated using Doppler echocardiography. Cardiac assessment by echocardiography and AVF flow measurement by Doppler ultrasound were done. Levels of TXB(2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in plasma were determined.. PHT was found in 44.4% in group 1 and in 32.3% in group 2. Comparing the two groups shows a significant difference with regard to PAP, proBNP, and TXB(2). Patients with PHT have a significantly higher AVF blood flow, proBNP, and TXB(2). In patients with PHT, 76.7% have left ventricular diastolic dysfunction (LVDD). PAP correlates with AVF flow, proBNP, and TXB(2).. Results show a high prevalence of PHT among patients with ESRD on chronic HD or on conservative treatment. PHT in such patients is related to AVF flow, TXB(2) and NT-proBNP level and LVDD. AVF flow is an important correctable cause of PHT.

Topics: Adult; Aged; Arteriovenous Fistula; Blood Pressure; Echocardiography, Doppler; Female; Humans; Hypertension, Pulmonary; Kidney Failure, Chronic; Male; Middle Aged; Natriuretic Peptide, Brain; Radioimmunoassay; Thromboxane B2

Pulmonary arterial hypertension (PAH) is a term used to define a variety of progressive conditions that have in common, increased pulmonary vascular resistance leading to right heart failure and death. There has been considerable decrease in mortality and morbidity with the advances in PAH treatment over the past decade. However, since there is no epidemiologic study in Turkey, the prevalence of PAH and its importance is not known yet. This study aimed to evaluate the diagnostic clinical experience of Ege University Medical School Cardiology Department with PAH patients.. We evaluated the diagnostic approach to patients referred to our department with the diagnosis of PAH since 2000 by retrospective analysis method.. The diagnosis of pulmonary hypertension was definite in 70 patients (mean age 47+/-16 years, 61% women). Etiology from most prevalent to least was as following: congenital heart diseases (27%), chronic thromboembolic pulmonary hypertension (24%), connective tissue diseases-scleroderma (14%), idiopathic PAH (8%), diastolic dysfunction (3%), pulmonary disease (3%), pulmonary veno-occlusive disease (2%), hepatopulmonary hypertension (1%), and HIV-infection associated PAH (1%). At diagnosis, 68% of patients were in NYHA functional class-III or IV. Six-minute walk test was 263+/-127 m. Mean pulmonary artery pressure was 65+/-20 mmHg. The prognostic marker pro-BNP (brain natriuretic peptide) level was 3208+/-4145 pg/ml.. Our practice shows that PAH is diagnosed late in the course of the disease in Turkey. This can be overcome with structured management in designated centers with multidisciplinary team-working in a shared care approach. There is also an urgent need for an epidemiological registry in order to determine the burden of PAH in Turkey and increase the awareness of doctors.

Topics: Biomarkers; Exercise Tolerance; Female; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prevalence; Prognosis; Retrospective Studies; Scleroderma, Systemic; Turkey

Bosentan, an endothelin (ET) ETA-ETB receptors antagonist, is an effective therapy for idiopathic pulmonary arterial hypertension (PAH) and for PAH related to connective tissue disease (CTD). The aim of this study was to evaluate the behaviour of ET-1 and brain natriuretic peptide (BNP) venous plasma levels during a 6-month dual ET-1 receptor blockade and the potential influence of baseline ET-1 venous plasma levels on the clinical efficacy of bosentan.. Twenty-five patients with PAH (idiopathic n=16, CTD n=9) in WHO functional class II-III were included in this study. After initial evaluation, patients' WHO class, 6-minute walking-test (6MWT), ET-1 and BNP venous plasma levels were assessed at baseline and after 6-month bosentan therapy. To evaluate whether the ET-1 levels could influence the clinical response to bosentan, data were analyzed for the whole population which was stratified according to high and low ET-1 plasma levels (on the basis of the baseline median value of ET-1 plasma: Gr.1<18.7 pg/ml, Gr.2>18.7 pg/ml).. Study population included patients with moderate-severe PAH. After 6-month of treatment we observed a significant increase in 6MWT distance (from 435+/-85) m to 467+/-77 m, p>0.001) and an improvement in WHO class (from 2.4+/-0.5 to 2+/-0.6 p>0.01), with a significant decrease in BNP (from 87+/-33 pg/ml to 67+/-41 pg/ml, p=0.006) and a trend towards lower ET-1 plasma levels (from 17.7+/-5 pg/ml to 16+/-6 pg/ml, p=ns). Improvement in effort tolerance (Delta distance) was not correlated to modification in ET-1 (DeltaET-1) and BNP (DeltaBNP) plasma levels, while we found a significant correlation between DeltaET-1 and DeltaBNP (r=0.63, p=0.0006). Analyzing the subpopulation, Gr.2 patients were older (Gr.1: 41+/-10 years vs Gr.2: 50+/-9 years, p=0.04), had less effort capacity (6MWT distance, Gr.1: 469+/-76 m, vs Gr.2: 398+/-82 m, p=0.03), and showed a trend towards higher BNP values (Gr.1: 82+/-41 pg/ml vs Gr.2: 92+/-23 pg/ml, p=0.051), but no significant differences in pulmonary hemodynamics. After the 6-month treatment both groups showed a significant improvement in 6MWT (Gr.1: +32+/-24 m, Gr.2: +32+/-21 m p=0.05) without differences between groups. WHO class had a trend towards lower class (Gr.1: -0.5+/-0.5, Gr.2: -0.3+/-0.4 p=0.15) in both groups. BNP plasma levels showed a significant decrease only in Gr.2 (Gr.1: -6+/-41 pg/ml, Gr.2: -34+/-19 pg/ml p=0.02); similarly ET-1 plasma levels showed a trend towards a decrease only in Gr.2 (Gr.1: 0.2+/-4.6 pg/ml, Gr.2: -3.8+/-6.6 pg/ml p=0.09).. Our data confirm that bosentan is an effective therapy for patients with PAH. Its clinical efficacy (effort tolerance and NYHA) seems to be independent from baseline venous ET1 plasma levels. Bosentan therapy seems to elicit different patterns in ET-1 and BNP plasma levels, with decrease of the peptides only in patients with higher activation of the systemic endothelin system. Further studies are warranted to explore the potential impact of baseline ET-1 levels on the long-term effects (clinical worsening) of bosentan therapy.

Topics: Adult; Antihypertensive Agents; Bosentan; Endothelin A Receptor Antagonists; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Sulfonamides; Time Factors

Pulmonary hypertension (PHT) occurs in approximately 30% of adults with sickle cell disease (SCD) and is an independent risk factor for early death. In this study, we aimed to determine the value of general laboratory testing, plain chest radiography, electrocardiography (ECG), high-resolution computer tomography (HRCT) of the thorax, pulmonary function testing, and plasma N-terminal brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) in patients with SCD-related PHT. A cohort of 85 ambulatory sickle cell patients were prospectively screened for PHT with echocardiography (defined as a tricuspid regurgitation flow velocity of > or =2.5 m/sec). All patients were systematically evaluated by the aforementioned diagnostic tests comparing patients with and without PHT. The prevalence of PHT was 41% in HbSS/HbSbeta(0)-thalassemia patients and 13% in HbSC/HbSbeta(+)-thalassemia patients. No statistically significant differences were detected in ECG, chest radiography, HRCT, and pulmonary function testing between patients with and without PHT. The degree of anemia and renal dysfunction, but not the presence of PHT, were the most important determinants of plasma (NT-pro)BNP levels. The performed imaging and functional studies do not seem to be of value in identifying etiological conditions (such as airflow obstruction or parenchymal lung disease) nor do they offer clues to the presence of mild PHT in SCD.

Topics: Adult; Anemia, Sickle Cell; Cohort Studies; Electrocardiography; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Respiratory Function Tests; Tomography, X-Ray Computed

B-type natriuretic peptide (BNP) reflects volume overload on left ventricle and pulmonary hypertension (PH) in patients with ventricular septal defect (VSD). Pulmonary vascular resistance (PVR) has been reported to correlate positively with BNP in VSD patients with various degrees of PH. We aimed to investigate the relationship between PVR and BNP in VSD patients with severe PH. We examined 24 subjects with VSD concomitant severe PH aged from 2 months to 17 years (median: 4 months). The ratio of pulmonary to systemic pressure (Pp/Ps), the ratio of pulmonary to systemic flow (Qp/Qs), the ratio of pulmonary to systemic resistance (Rp/Rs), and PVR were determined by cardiac catheterization. PVR and Rp/Rs ranged from 1.6 to 15.5 (mean: 5.7 +/- 3.9) Wood unit . m(2) and 0.1 to 0.8 (mean: 0.4 +/- 0.2), respectively. BNP ranged from 5.5 to 69 (mean: 31 +/- 19) pg/ml. Negative correlations were observed between BNP and PVR (r = -0.56, p = 0.004) and BNP and Rp/Rs (r = -0.51, p = 0.01). BNP was significantly lower (<10 pg/ml) in VSD patients with Eisenmenger physiology as compared with the others (p = 0.003). We should draw attention to evaluate BNP values in VSD patients with severe PH.

Topics: Adolescent; Cardiac Catheterization; Child; Child, Preschool; Comorbidity; Echocardiography, Doppler; Eisenmenger Complex; Female; Heart Septal Defects, Ventricular; Hemodynamics; Humans; Hypertension, Pulmonary; Infant; Male; Natriuretic Peptide, Brain; Vascular Resistance

Systemic sclerosis (SSc) is characterized by vascular dysfunction that may lead to pulmonary artery hypertension (PAH). The N-terminal pro-B type natriuretic peptide (NT-proNBP), a marker of cardiac failure, is a diagnostic marker of early PAH in patients with SSc without heart failure. Our aim was to determine whether NT-proBNP levels may be a useful tool to evaluate the response to bosentan therapy in patients with PAH secondary to SSc. Ten patients with symptomatic, severe PAH secondary to SSc, received bosentan, 62.5 mg twice a day for 4 weeks followed by 125 mg twice a day for 7 months. Ten patients with SSc without PAH served as controls for basal level of NT-proBNP. Blood samples were obtained before the beginning of the therapy and after 3 and 7 months of treatment. SSc patients with PAH had significantly higher serum levels of NT-proBNP than those without PAH, at baseline. After 3 and 7 months of therapy, NT-proBNP concentration showed a progressive decrease, nearly approaching statistical difference at 7 months when compared to baseline levels (P=0.953 and P=0.600). Our results show that serum NT-proBNP levels may be a useful marker for the response to bosentan therapy in patients with PAH secondary to SSc.

Topics: Adult; Aged; Bosentan; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Scleroderma, Systemic; Sulfonamides

In congenital diaphragmatic hernia (CDH) the severity of pulmonary hypertension (PH) is considered, by several authors, determinant of clinical outcome. Plasmatic N-terminal-pro-B type natriuretic peptide (NT-proBNP) might be useful in diagnosis and management of PH in newborns, although its interest in CDH infants remains to be defined. Early NT-proBNP levels were assessed in CDH infants and correlated with cardiovascular echocardiographic parameters.. 28 newborns, CDH and age-matched controls were enrolled in a prospective study. Clinical condition, NT-proBNP plasmatic levels, echo parameters of PH and biventricular function were assessed at 24 h after delivery as well as survival outcome.. Estimated mean pulmonary pressure and NT-proBNP were significantly higher in CDH than control infants. NT-proBNP significantly correlated with estimated pulmonary artery pressure, right ventricular Tei index, and tricuspid E/A ratio. Additionally, we found that CDH infants with NT-proBNP >11,500 pg/ml experienced a worse prognosis.. We demonstrated that PH is associated with NT-proBNP elevation and diastolic impairment in CDH infants. Early elevations in NT-proBNP levels seem to alert for a subset of CDH infants with worse prognosis.

Topics: Blood Pressure; Case-Control Studies; Echocardiography; Female; Heart; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Humans; Hypertension, Pulmonary; Infant, Newborn; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Severity of Illness Index

To evaluate predictors of pulmonary arterial hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc).. Routine clinical assessments as well as measurements of the diffusing capacity for carbon monoxide/alveolar volume (DLCO/VA) ratio and N-terminal pro-brain natriuretic peptide (NT-proBNP) level were performed in a prospective cohort of 101 SSc patients who did not have PAH or severe comorbidities. After a planned 36-month followup, we evaluated the predictive value of these parameters for the development of precapillary PAH, as demonstrated by cardiac catheterization, disease progression, and death. Criteria for cardiac catheterization were a systolic pulmonary artery pressure (PAP) of >40 mm Hg on echocardiography, a DLCO value of <50% without pulmonary fibrosis, and unexplained dyspnea.. Eight patients developed PAH, 29 had disease progression, and 10 died during a median followup of 29 months. Kaplan-Meier analysis identified the following baseline parameters as being predictors of PAH: DLCO/VA ratio <70% or <60% (P<0.01 for each comparison), elevated plasma NT-proBNP level (>97th percentile of normal; P = 0.005), echocardiographically estimated systolic PAP >40 mm Hg (P=0.08), and erythrocyte sedimentation rate >28 mm/hour (P=0.015). In multivariate analyses, an elevated baseline NT-proBNP level (hazard ratio [HR] 9.97 [95% confidence interval (95% CI) 1.69-62.42]) and a DLCO/VA ratio <60% (HR 36.66 [95% CI 3.45-387.6]) were predictors of the occurrence of PAH during followup. An increased NT-proBNP level together with a decreased DLCO/VA ratio of <70% was highly predictive of the occurrence of PAH during followup (HR 47.20 [95% CI 4.90-450.33]).. This prospective study identified a decreased DLCO/VA ratio and an increased NT-proBNP as predictors of PAH in SSc. Use of these markers should result in improved PAH risk stratification and allow earlier initiation of therapy.

Topics: Adult; Aged; Biomarkers; Capillaries; Carbon Monoxide; Comorbidity; Diffusion; Disease Progression; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Incidence; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Risk Factors; Scleroderma, Systemic; Severity of Illness Index

Steady-state mild pulmonary hypertension is a risk factor for death in adults with sickle cell disease. Acute pulmonary hypertension has been reported during exercise and vasoocclusive pain crisis in these patients.. The aim of the present study was to evaluate changes in pulmonary pressures and cardiac biomarkers during severe acute chest syndrome and their associations with mortality.. We prospectively evaluated 70 consecutive adults who received standardized treatment in our intensive care unit for a total of 84 episodes. At admission, cardiac biomarkers were measured. Transthoracic echocardiography was performed for pulmonary hypertension assessment via measurement of tricuspid regurgitant jet velocity and was repeated when possible after resolution.. Tricuspid jet velocity was less than 2.5 m/second in 34 (40%) of the 84 episodes, 2.5 to 2.9 m/second in 19 (23%), and 3 m/second or greater in 31 episodes (37%). Cor pulmonale occurred in 11 (13%) episodes. Tricuspid jet velocity showed significant positive correlations with B-type natriuretic peptide (rho = 0.54, P < 0.01) and cardiac troponin I (rho = 0.42, P < 0.01). Pulmonary pressures increased compared with steady state then decreased after resolution. All five patients who required invasive ventilation and all four patients who died during the immediate hospital course had jet velocity values of 3 m/second or greater. Overall mortality was 12.9% (9 patients) and survival was significantly lower in patients whose jet velocity was 3 m/second or greater during at least one episode, compared with the other patients (P < 0.01).. Pulmonary pressures increase during severe acute chest syndrome, and pulmonary hypertension is associated with cardiac biomarker elevation and a higher risk of death.

Topics: Adult; Anemia, Sickle Cell; Biomarkers; Blood Pressure; Echocardiography; Female; France; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Prospective Studies; Pulmonary Artery; Pulmonary Heart Disease; Respiratory Distress Syndrome

To determine whether elevated B-type natriuretic peptide (BNP) predicts left ventricular (LV) contractile dysfunction on exercise stress echocardiography in patients with severe mitral regurgitation (MR).. Thirty three patients with moderate-to-severe or severe MR, a LV ejection fraction > or =60% and New York Heart Association Class I or II symptoms, and 12 controls underwent resting and exercise stress echocardiography. In 20 MR patients, BNP was within the normal range (mean +/- SD, 7.7 +/- 2.7 pmol/L), and in 13 MR patients, BNP was >12 pmol/L (19.6 +/- 7.6 pmol/L). LV end-systolic volume index after exercise was lower in controls than patients with MR (P < 0.0001), but similar in MR patients with normal and elevated BNP, respectively (controls 8.5 +/- 3.9, MR 20 +/- 7 vs. 20 +/- 9 cm(2)/m(2), P > 0.05). However, pulmonary artery systolic pressure (PAP) after exercise was higher in MR with high BNP (70 +/- 20 vs. 48 +/- 11 mmHg, <0.0001) and controls (38+/-11 mmHg). A two-fold increase in plasma BNP was associated with an average increase in resting PAP of 7.6 (95% CI 2.9, 12.2) mmHg, an increase in post-exercise PAP of 14.4 (95% CI 9.0, 19.9) mmHg and increase in left atrial area index of 2.1 (95% CI 0.5, 3.8) cm(2)/m(2). However, there was no significant association between the plasma level of BNP and any rest or post-exercise measure of LV systolic function (r < 0.25, P > 0.05 for all).. The plasma level of BNP may be within the normal range in patients with moderate-to-severe or severe MR despite significant increases in LV end-systolic volume. Increase in BNP is associated with pulmonary artery hypertension on exercise and left atrial enlargement even when LV systolic function on exercise stress echocardiography is normal.

Topics: Case-Control Studies; Echocardiography, Stress; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Predictive Value of Tests; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

The purpose of our study was to investigate the effect of bosentan treatment on surrogate markers in patients with systemic-sclerosis-related pulmonary arterial hypertension (SScPAH). We studied ten SScPAH patients (nine female, median age 58 years, median duration of disease 9 years). Six-minute walk test (SMWT) and plasma N-terminal probrain natriuretic peptide (NT-proBNP) levels were recorded from patients at baseline and after 20 weeks under bosentan treatment. Wilcoxon paired signed rank test was applied in order to compare NT-proBNP levels and SMWT at baseline and week 20. At week 20, NT-proBNP levels were decreased from a median of 474 fmol/ml (range, 212-1407 fmol/ml) at baseline to 238 fmol/ml (range, 198-335 fmol/ml; p=0.002). Mean SMWT distance increased from a baseline median value of 323 m (range, 224-368 m) to 372 m (range, 232-530 m), representing a nonsignificant increase. Our results suggest that NT-proBNP is a biochemical surrogate marker, which could be used to evaluate the effects of bosentan or other vasodilation therapy in SScPAH.

Topics: Adult; Aged; Antihypertensive Agents; Biomarkers; Bosentan; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Scleroderma, Systemic; Sulfonamides

A 42-year-old woman with limited cutaneous systemic sclerosis presented with rapid-onset dyspnea on exertion, which had developed over the previous 8 weeks. She had not experienced any dyspnea before this period. Transthoracic Doppler echocardiography performed 6 months before presentation demonstrated an estimated right ventricular systolic pressure of 32 mmHg. Lung function tests also performed at that time revealed a decreased diffusion capacity for carbon monoxide of 54% and normal lung volumes, and high-resolution CT scan of the lungs was normal.. Physical investigation, CBC, analysis of C-reactive protein and pro-brain natriuretic peptide, transthoracic Doppler echocardiography, six-minute walk test, lung function tests including diffusion capacity for carbon monoxide, right heart catheter, high-resolution CT scan, and ventilation/perfusion scan.. Pulmonary arterial hypertension associated with limited cutaneous systemic sclerosis.. Treatment with oral anticoagulation therapy and the endothelin-receptor antagonist bosentan. Monitoring of adverse effects of bosentan therapy was performed using liver function tests.

Topics: Adult; Antihypertensive Agents; Bosentan; Dyspnea; Echocardiography; Exercise Test; Female; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Respiratory Function Tests; Scleroderma, Systemic; Sulfonamides

Elevated serum brain natriuretic peptide (BNP) released from myocytes of ventricles upon stretch have been found in patients with isolated right ventricular (RV) pressure overload. However, limited data suggest that serum BNP may be elevated in systemic sclerosis (SSc) patients, especially with RV dysfunction. We assessed serum N-terminal proBNP (NT-proBNP) in SSc and evaluated whether it reflects the severity of RV overload. We prospectively studied 51 consecutive patients (47F, mean age 53.3 +/- 15.2 years) with SSc (mean disease duration 9 +/- 12.4 years). The control group formed 31 healthy subjects (27F, mean age 52.6 +/- 12.1 years). NT-proBNP level, 6-minute walking test (6MWT), and transthoracic echocardiography (TTE) for the assessment of RV overload were performed. Serum NT-proBNP exceeded the reference value of 125 pg/mL in 31 (61%) SSc patients. The mean serum log NT-proBNP concentration in SSc was higher than in controls (2.138 +/- 0.527 vs. 1.634 +/- 0.420 pg/mL, p < 0.001). 13 (25%) SSc patients have tricuspid regurgitation peak gradient (TRPG) exceeding 31 mmHg reflecting pulmonary arterial hypertension (PAH). The SSc presented other echocardiographic signs of RV overload. Mean 6MWT distance was shorter in SSc than in controls (528 +/- 100 vs. 617 +/- 80 m, p < 0.001). NT-proBNP level correlated positively with TRPG, RV diameter, RV Tei index and negatively with 6MWT distance. ROC analysis identified >115 pg/ml as the best NT-proBNP threshold predicting PAH for SSc patients (sensitivity 92%, specificity 44%). Results of our study suggest that NT-proBNP measurement is a useful screening method for PAH in SSc patients. Since elevated plasma NT-proBNP level reflects the degree of right ventricular overload and limitation of exercise capacity, abnormal NT-proBNP levels should imply further evaluation including echocardiography.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Echocardiography; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Scleroderma, Systemic; Ventricular Dysfunction, Right

Appropriate parameters are needed for the monitoring of children with pulmonary arterial hypertension (PAH). Various biologic markers seem to be of use in adults with PAH. No data are available on their value in children with PAH. In this study, the relation between serum markers, functional parameters, and hemodynamic variables in pediatric PAH and their ability to predict survival is determined. Serum N-terminal pro brain natriuretic peptide (NT-proBNP), uric acid, norepinephrine, and epinephrine were measured and correlated with invasive hemodynamics, functional parameters, and outcome in 29 pediatric patients with PAH who visited a tertiary reference center for pediatric PAH between 1997 and 2005. NT-proBNP correlated with functional class (R = 0.36; p = 0.03) and 6-min walking distance (6MWD) (R = -0.53; p < 0.001). Uric acid correlated with mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac index (R = 0.63, p = 0.01; R = 0.71, p = 0.03, and R = -0.65, p = 0.007, respectively). After initiation of treatment, NT-proBNP decreased. This decrease correlated with an increased 6MWD. Finally, norepinephrine and NT-proBNP levels were highly predictive for mortality. In this series of children with PAH, biologic markers were correlated with hemodynamics and functional capacity, as parameters of disease severity. The data indicate that these markers can be used to monitor treatment effects and predict mortality in pediatric PAH.

Topics: Adolescent; Biomarkers; Blood Pressure; Cardiac Output; Cardiovascular Agents; Child; Child, Preschool; Drug Monitoring; Epinephrine; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Infant; Male; Natriuretic Peptide, Brain; Norepinephrine; Peptide Fragments; Predictive Value of Tests; Pulmonary Artery; Recovery of Function; Reproducibility of Results; Severity of Illness Index; Treatment Outcome; Uric Acid; Vascular Resistance; Walking

Topics: Biomarkers; Electrocardiography; Heart Arrest; Heart Failure; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Prognosis; Pulmonary Embolism; Radionuclide Imaging; Troponin I; Troponin T; Ultrasonography

In congenital diaphragmatic hernia (CDH), pulmonary hypertension increases right ventricle (RV) afterload, which could impair heart function and contribute to poor outcome for most affected infants. Nevertheless, the real significance of vascular pulmonary alterations in perinatal hemodynamics is largely unknown. It is defined that ventricular pressure overload induces increased myocardium gene expression of B-type natriuretic peptide (BNP) and components of the renin-angiotensinogen and endothelin (ET)-1 systems. Our aim was to evaluate perinatal myocardium expression of these genes associated with ventricular pressure overload in a nitrofen-induced CDH rat model.. In the nitrofen-induced CDH rat model, fetuses from dated pregnant Sprague-Dawley rats at 15.5, 17.5, 19.5 and 21.5 days postcoitum as well as newborn pups were assigned to 3 experimental groups: control, nitrofen (exposed to nitrofen, without CDH), and CDH (exposed to nitrofen, with CDH). Myocardial samples collected from the RV and left ventricle (LV) were processed for quantification of messenger RNA (mRNA) of BNP, angiotensinogen, and ET-1.. The perinatal expression of BNP, angiotensinogen, and ET-1 mRNA in the RV and LV of the control group revealed daily changes. During gestation, the expression of BNP and angiotensinogen mRNA underwent significant oscillation compared with control in both nitrofen-exposed fetuses, although we cannot identify significant differences between the nitrofen and CDH groups. After birth, we found a significant increasing expression of all studied genes only in the RV of CDH pups.. Perinatal myocardial quantification of BNP, angiotensinogen, and ET-1 mRNA levels suggests that both nitrofen-exposed and control pups revealed prenatal variations of expression of the studied genes. Moreover, CDH is associated with significant molecular alterations only in the RV after birth.

Topics: Adaptation, Biological; Angiotensinogen; Animals; Base Sequence; Biomarkers; Endothelin-1; Gene Expression; Genetic Markers; Heart Ventricles; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Hypertension, Pulmonary; Molecular Sequence Data; Myocardium; Natriuretic Peptide, Brain; Phenyl Ethers; Rats; Rats, Sprague-Dawley; RNA, Messenger

The recent development of treatment modalities for patients with idiopathic pulmonary arterial hypertension has been based on the evaluation of many different markers such as functional capacity, addressed by NYHA classification, six-minute walk test (6MWT) and hemodynamic parameters. The aim of this study was to evaluate the correlation of N-terminal fragment (NT-proBNP) with other markers in IPAH and its potential for patient stratification. We studied 42 IPAH patients consecutively evaluated through right heart catheterization in the absence of any specific treatment for pulmonary hypertension. Blood samples, clinical evaluation and 6MWF distance were collected at baseline. The levels of NT-proBNP showed a high correlation with hemodynamic parameters, such as pulmonary vascular resistance (r=0.80, P<0.001). A significant difference was found among patients with different functional classes, addressed by NYHA classification (P< 0.02 for all groups comparison). The discriminant analysis reinforced the ability of NT-proBNP to stratify patients according to NYHA functional class. Compared to the other variables studied (hemodynamics and 6MWT), NT-proBNP had the lowest level of overlap in the stratification of IPAH patients. We conclude that NT-proBNP differs among the different functional classes and correlates with other measures of disease severity, although its role in predicting survival still needs to be addressed.

Topics: Adult; Analysis of Variance; Biomarkers; Cardiac Catheterization; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Lung; Male; Natriuretic Peptide, Brain; Peptide Fragments; Regression Analysis; Sensitivity and Specificity; Vascular Resistance

Systemic sclerosis (SSc) is a connective tissue disease, which may lead to pulmonary artery hypertension (PAH). N-terminal pro-brain natriuretic peptide (NT-proBNP) is a biologic marker for the diagnosis and treatment of congestive heart failure. The aim of our study was to investigate the potential role of the plasma NT-proBNP assay in the assessment of functional status and right heart performance in systemic sclerosis-related pulmonary hypertension (SScPAH). Systolic pulmonary artery pressure (sPAP) assessed by echocardiography, six-minute walk test (SMWT) and plasma NT-proBNP levels were recorded from 45 SSc patients. Mean value of NT-proBNP for SSc patients with PAH (n=14) was 691.7+/-325.7 fmol/L compared to 417.4+/-167.1 fmol/L for patients without PAH (n=31) (p=0.0007). In SSc patients we found a statistically significant correlation between NT-proBNP values and sPAP (r=0.32, p=0.03). Amongst SScPAH patients, NT-proBNP values were significantly correlated with sPAP (r=0.73, p=0.003) and inversely correlated with the SMWT (r=-0.60, p=0.02). These results suggest NT-proBNP as a useful additional biological tool in the evaluation and management of SScPAH patients.

Topics: Biomarkers; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Scleroderma, Systemic; Severity of Illness Index; Ultrasonography

Right ventricular systolic dysfunction (RVSD) at baseline (pre-treatment) predicts early death in patients with pulmonary hypertension (PH). However, RVSD can only be detected reliably by prohibitively invasive or expensive techniques. N-terminal B-type natriuretic peptide concentration ([NT-proBNP]) correlates with RV function in PH; however, an [NT-proBNP] threshold that indicates RVSD in individual patients has not previously been determined. Twenty-five patients with PH (pulmonary arterial hypertension (n = 19) or chronic thromboembolic PH (n = 6)) underwent cardiovascular magnetic resonance (CMR) imaging and NT-proBNP measurement at baseline. [NT-proBNP] was correlated against RV dimensions and ejection fraction (RVEF) measured directly by CMR imaging. The ability of NT-proBNP to detect RVSD (defined as a CMR-derived RVEF >2 SDS below control values) was tested and predictors of [NT-proBNP] identified. [NT-proBNP] correlated negatively with RVEF. RVSD was present in nine out of 25 patients. An [NT-proBNP] threshold of 1,685 pg.mL(-1) was sensitive (100%) and specific (94%) in detecting RVSD. RVEF and RV mass index independently predicted [NT-proBNP]. In pulmonary hypertension, a baseline N-terminal B-type natriuretic peptide concentration of >1,685 ng.L(-1) suggests right ventricular systolic dysfunction, and thus an increased risk of early death. N-terminal B-type natriuretic peptide could prove useful as an objective, noninvasive means of identifying patients with pulmonary hypertension who have right ventricular systolic dysfunction at presentation.

Topics: Aged; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Pulmonary Artery; Ventricular Function, Right

Topics: Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Scleroderma, Systemic

In chronic thromboembolic pulmonary hypertension, objective data to assess the functional outcome after pulmonary endarterectomy are lacking. We studied the 6-minute walk distance in relation to the clinical and hemodynamic severity of disease, and assessed the effect of pulmonary endarterectomy on the 6-minute walk distance.. A total of 50 consecutive patients with chronic thromboembolic pulmonary hypertension were studied. Subsequently, pulmonary endarterectomy was performed in 42 patients, 35 of whom underwent a 6-minute walk distance 1 year after surgery.. The mean +/- standard error of the mean 6-minute walk distance was 391 +/- 19 m. The 6-minute walk distance decreased in proportion to New York Heart Association functional class and correlated (all P < .0001) with mean pulmonary artery pressure (r = -0.62), cardiac output (r = 0.76), total pulmonary resistance (r = -0.75), mixed venous oxygen saturation (r = 0.77), and brain natriuretic peptide (r = -0.65). One year after pulmonary endarterectomy, the 6-minute walk distance increased from 417 +/- 19 m to 517 +/- 16 m (P < .0001). The change from baseline in 6-minute walk distance correlated with the changes after 1 year in New York Heart Association functional class (P < .01) and brain natriuretic peptide (r = 0.57, P < .002), and with the observed hemodynamic changes directly after pulmonary endarterectomy (change in mean pulmonary artery pressure: r = 0.52; change in cardiac output: r = 0.70; change in total pulmonary resistance r = 0.70; all P < .001). In patients with residual pulmonary hypertension after pulmonary endarterectomy, the 6-minute walk distance was significantly lower than in hemodynamically normalized patients. However, the absolute increase in the 6-minute walk distance was higher in patients with residual pulmonary hypertension (137 +/- 26 m and 82 +/- 20 m, respectively; P = .03).. The 6-minute walk distance was demonstrated to reflect the clinical and hemodynamic severity of disease in patients with chronic thromboembolic pulmonary hypertension. One year after pulmonary endarterectomy, the 6-minute walk distance had increased significantly, and the change in the 6-minute walk distance correlated with the observed clinical and hemodynamic improvement.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chronic Disease; Cohort Studies; Endarterectomy; Exercise Test; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Prospective Studies; Pulmonary Circulation; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Survival Rate; Thromboembolism; Time Factors; Treatment Outcome; Vascular Patency; Walking

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a byproduct of the brain natriuretic peptide (BNP) that was shown to be of prognostic value in pulmonary hypertension (PH). The role of NT-proBNP in PH has to be determined, especially under the influence of renal impairment that might lead to an accumulation of the peptide, and may be a sign of increased mortality per se.. We assessed NT-proBNP, BNP, renal function, and hemodynamic parameters (during right-heart catheterization) in 118 consecutive patients with isolated PH, excluding left-heart disease. Depending on the calculated creatinine clearance, patients were classified into different groups of renal function. Correlation analysis was performed on all key parameters. Results were then compared between the levels of renal function. The prognostic value of each parameter was assessed during a mean follow-up period of 10 months.. Twenty-two patients (approximately 19%) had significantly impaired renal function (creatinine clearance < 60 mL/min). Although the overall levels of NT-proBNP were correlated with hemodynamics, we observed no correlation in the group with significant renal dysfunction. Moreover, NT-proBNP was related to creatinine clearance. Finally, NT-proBNP and renal insufficiency were independent predictors of death during univariate and multivariate analysis, whereas BNP only predicted mortality in univariate analysis.. The diagnostic accuracy of NT-proBNP as a parameter of the hemodynamic status is diminished by renal function. However, NT-proBNP could be superior to BNP as a survival parameter in PH because it integrates hemodynamic impairment and renal insufficiency, which serves as a sign of increased mortality per se.

Topics: Biomarkers; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Renal Insufficiency; Risk Factors; Survival Rate

Topics: Animals; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Ventricular Function, Right

The authors describe a case of 21-years old woman with idiopathic pulmonary arterial hypertension with atypical clinical consequences of massive internal bleeding. Despite significant hypovolemia clinical and laboratory presentation was one of RV failure with dilatation of right heart ventricle and increased plasma level of markers of myocardial stretch and injury (NT-proBNP and troponin, respectively). This is attributed to impaired right ventricular coronary perfusion and hypoxia. Intensive treatment restored baseline RV conditions and at 15 months follow-up no persistent right heart impairment was observed. This case demonstrates that bleeding should be also considered in differential diagnosis of exacerbation of right ventricular failure in patients with pulmonary arterial hypertension.

Topics: Adult; Biomarkers; Female; Heart Failure; Hemoperitoneum; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T; Ventricular Dysfunction, Right

Pulmonary hypertension (PH) is increasingly observed in sickle cell disease (SCD) and beta-thalassemia (beta-thal), but there is no information on its prevalence in patients with HbS/beta-thal. The amino-terminal fragment of B-type natriuretic peptide (NT-proBNP) is considered as an independent prognostic factor in PH. The aim of this study was to evaluate the incidence of PH and its correlation with clinical and laboratory findings, including NT-proBNP, in patients with HbS/beta-thal.. We studied 84 HbS/beta-thal patients; 51% had been receiving hydroxyurea for a median time of 9 years. The presence of PH was evaluated using Doppler echocardiography and NT-proBNP serum levels were determined by an electrochemiluminescence immunoassay.. The incidence of PH in our cohort of HbS/beta-thal patients was 33%. PH patients had elevated values of NT-proBNP, reticulocyte counts and serum ferritin compared with patients without PH. However, even patients without PH had elevated concentrations of NT-proBNP compared with controls. An NT-proBNP level of 153.6 pg/mL had the highest sensitivity (85.7%) and specificity (94.6%) for detecting PH in our patients. NT-proBNP levels correlated with measures of pulmonary artery systolic pressure (tricuspid regurgitant jet velocity and right ventricular systolic pressure), left atrial area and diastolic dysfunction. The administration of hydroxyurea did not affect the presence of PH.. The incidence of PH in patients with HbS/beta-thal is similar to that observed in patients with SCD. Serum NT-proBNP is a strong indicator of PH in HbS/beta-thal. The correlation between PH and reticulocyte counts and ferritin suggests that the degree of hemolysis and iron overload is implicated in the pathogenesis of PH in HbS/beta-thal.

Topics: Adult; Anemia, Sickle Cell; beta-Thalassemia; Case-Control Studies; Female; Ferritins; Humans; Hydroxyurea; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Reticulocyte Count

The diagnosis of right heart failure and pulmonary hypertension in cystic fibrosis (CF) patients with advanced pulmonary disease is sometimes difficult on clinical grounds alone. B-type natriuretic peptide (BNP) & N-terminal pro-B-type natriuretic peptide (N-BNP) levels were found to be useful in differentiating heart failure from various pulmonary diseases. However, its level was never measured in CF patients. The aim of this study was to measure N-BNP level in CF patients without heart failure.. The study included 49 patients. Of these, 32 had CF and 17 were control subjects who were matched by age and sex variables to the study group. We looked for a correlation between N-BNP and lung function test, genetic profile, height percentiles, and weight percentiles. N-BNP level was measured using an immunoassay that contains polyclonal antibodies that recognize epitopes located in the N-terminal part of proBNP.. N-BNP level among CF patients without heart failure, after age and sex adjustments, was similar to the control group (Median: 47 pg/ml vs. 38 pg/ml, P = 0.248, interquartile range: 33-99 pg/ml vs. 31-76 pg/ml). A correlation between N-BNP level to age was found in both groups (CF: R = -0.398; P = 0.024, CONTROL: R = -0.054; P = 0.024). There was no correlation between N-BNP level to FEV1, O2 saturation and nutritional status. Among CF patients, eight (25%) had a mildly elevated N-BNP level whereas none was found in the control group (P = 0.038).. We conclude that N-BNP level among CF patients is similar to the normal population and that it has no correlation to lung function impairment. Therefore, measurement of elevated N-BNP level in CF patients might be a predictor to the development of pulmonary hypertension and heart failure.

Topics: Adolescent; Adult; Child; Child, Preschool; Cystic Fibrosis; Forced Expiratory Volume; Heart Failure; Humans; Hypertension, Pulmonary; Immunoassay; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Right ventricular (RV) dysfunction is associated with increased morbidity and mortality in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo pulmonary endarterectomy (PEA). We studied whether plasma brain natriuretic peptide (BNP) levels can be used to identify RV dysfunction in CTEPH patients. Therefore, plasma BNP levels were studied in relation to cardiac remodeling and function as determined by cardiac magnetic resonance imaging (MRI).. Thirty-eight patients with CTEPH (55 +/- 15 years), and ten healthy controls (46 +/- 15 years) were studied. The BNP was determined by an immunoradiometric assay.. The CTEPH patients had a mean pulmonary artery pressure of 49 +/- 13 mm Hg, cardiac index 2.1 +/- 0.7 l x min(-1) x m(-2), and pulmonary vascular resistance of 867 +/- 432 dynes x s x cm(-5). In CTEPH patients, compared with controls, right ventricular (RV) remodeling was demonstrated. In the patients, BNP was increased and correlated (all p < 0.0001; Spearman rank test) with MRI parameters of RV remodeling and function: end diastolic (r = 0.71) and end systolic (r = 0.74) volumes, RV mass (r = 0.68), leftward ventricular septal bowing (r = -0.80) and ejection fraction (EF; r = -0.81). By receiver operating curve analysis, BNP levels of 11.5 picomole (pmol)/L and 48.5 pmol/L, respectively, detected RV dysfunction as defined by RVEF less than 0.45 and less than 0.30, respectively, with high sensitivity and specificity. Hemodynamically, BNP levels greater than 48.5 pmol/L identified the most severely affected patients.. In CTEPH patients, BNP levels correlate with RV remodeling and can be used to identify RV dysfunction. Future studies are warranted on the role of BNP to identify "high risk" CTEPH patients and its relation to postoperative hemodynamic outcome, RV failure, and mortality.

Topics: Adult; Aged; Atherectomy; Biomarkers; Cardiac Catheterization; Chronic Disease; Female; Heart Ventricles; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pulmonary Artery; Thromboembolism; Ventricular Dysfunction, Right

IV epoprostenol is a highly effective therapy for pulmonary arterial hypertension (PAH). However, monitoring the efficacy and adjusting the dose of epoprostenol often requires serial invasive hemodynamic measurements. This study investigated whether superior vena cava (SVC) oxygen saturation measured from the indwelling catheter and brain natriuretic peptide (BNP) level would predict right heart catheterization markers associated with lower survival rates (right atrial pressure [RAP], > 10 mm Hg; pulmonary artery [PA] oxygen saturation, < 62%) in epoprostenol-treated patients with PAH.. Twenty-seven epoprostenol-treated PAH patients had a BNP level and SVC oxygen saturation measured from their indwelling central venous catheters. The results were compared with cardiac catheterization results.. SVC oxygen saturation and BNP level both showed significant correlation with hemodynamic variables. BNP level correlated best with RAP (r = 0.66; p < 0.001), while SVC oxygen saturation correlated most closely with PA oxygen saturation (r = 0.91; p < 0.001). All patients with a BNP level of >or= 117 pg/mL had an elevated RAP (specificity, 100% [defined as a RAP of > 10 mm Hg]), but sensitivity was only 65%. An SVC oxygen saturation of < 64% showed a sensitivity of 89% and a specificity of 78% in predicting a PA oxygen saturation of < 62%.. SVC oxygen saturation and BNP level predict hemodynamics associated with lower survival rates and may be useful as "noninvasive" markers of prognosis in epoprostenol-treated PAH patients. BNP levels have a lower sensitivity relative to specificity, and a normal BNP level did not exclude a high RAP or low PA oxygen saturation.

Topics: Antihypertensive Agents; Blood Gas Analysis; Cardiac Catheterization; Cardiac Output; Catheterization, Central Venous; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Male; Natriuretic Peptide, Brain; Oxygen; Predictive Value of Tests; Prospective Studies; Pulmonary Artery; Pulmonary Wedge Pressure

Topics: Clinical Trials as Topic; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Practice Patterns, Physicians'

This study aims to evaluate the role of NT-proBNP and six minute walking distance (6MWD) in the pre- and post-operative assessment of subjects undergoing pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH).. Subjects undergoing PEA between August 2004 and July 2006 were assessed at baseline and 3 months post-operatively with resting haemodynamics, NT-proBNP and 6MWD.. A number of 111 subjects underwent surgery, of which 102 were included. 15 subjects died before their 3 month assessment. Non-survivors had significantly worse preoperative NT-proBNP and 6MWD (4728 pg/mL vs 1863 pg/mL, p=0.001, 182.4 m vs 263.5 m, p=0.001). Taking pre-operative cut-off values of 1200 pg/mL for NT-proBNP and 345 m for 6MWD, both tests had high negative predictive value for predicting mortality (97.3% and 100%, respectively). Amongst survivors, peri-operative changes in NT-proBNP and 6MWD correlated with changes in total pulmonary resistance (TPR) (r=0.49, p<0.001 and r=-0.46, p<0.001). Post-operatively, both NT-proBNP and 6MWD also correlated with mPAP (r=0.65, p<0.001 and r=-0.50, p<0.001) and PVR (r=0.63, p<0.001 and r=-0.47, p<0.001). The ability of NT-proBNP to predict persistent pulmonary hypertension was significantly confounded by age, but not gender, BMI or renal function.. Pre-operative evaluation with NT-proBNP and 6MWD helps risk-stratify patients prior to PEA. Post-operatively, both markers correlate with changes in disease burden and right ventricular function. These results suggest that both NT-proBNP and 6MWD offer effective 'bedside' tools for the long term follow up of patients with CTEPH.

Topics: Aged; Chronic Disease; Endarterectomy; Exercise Tolerance; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Patient Selection; Peptide Fragments; Postoperative Period; Predictive Value of Tests; Pulmonary Artery; Pulmonary Embolism; Time Factors; Ventricular Dysfunction, Right; Ventricular Pressure

Atrial septostomy has improved haemodynamics and clinical symptoms in selected patients with idiopathic pulmonary arterial hypertension. We found that, in 5 patients with idiopathic pulmonary arterial hypertension, septostomy resulted in decreased levels of brain-type natriuretic peptide, and improvement in symptoms of cardiac failure, suggesting that serial measurements of the peptide may have clinical utility.

Topics: Adolescent; Adult; Female; Heart Atria; Heart Septum; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain

There is little data on the long-term effects of continuous intravenous epoprostenol for children with idiopathic pulmonary arterial hypertension (IPAH) in Japan.. Thirty-one IPAH patients younger than 18 years old who had begun epoprostenol therapy at Toho University Omori Medical Center between January 1999 and June 2004 were reviewed. During a mean follow up of 3.4 years, the rate of those who survived or did not undergo a lung transplantation among the 27 patients who received home infusion therapy of epoprostenol was 100% at 1 year, 96.3% at 2 years, and 79.4% at 3 years. In 82% of survivors, the World Health Organization functional class was changed from III or IV to II according to improvements in the plasma brain natriuretic peptide level and the distance walked in 6 min during the follow-up period. In most cases, mean pulmonary artery pressure and the ratio of pulmonary to systemic vascular resistance remained high, although the cardiac index had improved to within a normal range 1 year after the initiation of epoprostenol. Therefore, sildenafil was administered as an additional therapy to 16 patients who presented with sustained severe PAH.. Continuous IV epoprostenol certainly improves survival and exercise tolerance in childhood IPAH, although the improvement of pulmonary vascular resistance regardless of long-term epoprostenol therapy is insufficient. Therefore, the addition of a new drug, such as sildenafil, is recommended to be administered in adjunction with epoprostenol.

Topics: Adolescent; Antihypertensive Agents; Blood Pressure; Child; Child, Preschool; Dose-Response Relationship, Drug; Epoprostenol; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Infusions, Intravenous; Japan; Natriuretic Peptide, Brain; Retrospective Studies; Treatment Outcome

Sildenafil and bosentan were added recently to the treatment with great expectations, effectiveness for the acute exacerbation of pulmonary arterial hypertension (PAH) is not fully examined. Two cases of acutely exacerbated PAH associated with collagen vascular diseases were treated first with sildenafil for six months followed by bosentan for another six months and the characteristics of this treatment modality were examined. Sildenafil showed an immediate effect which started in as early as approximately 30 min and was maximized in 60-90 min after oral ingestion. Continuous use of sildenafil for six months lowered pulmonary arterial pressure, pulmonary vascular resistance and the levels of brain natriuretic peptides along with an increased distance in 6-minute-walk, and replacement of it to with bosentan kept these effects. We think it as a treatment choice to use sildenafil first as a reliever and replace it with a controller bosentan, considering the immediate effects of sildenafil.

Topics: Adult; Antihypertensive Agents; Bosentan; Drug Therapy, Combination; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Lupus Erythematosus, Systemic; Mixed Connective Tissue Disease; Natriuretic Peptide, Brain; Piperazines; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Vasodilator Agents

Left ventricular (LV) diastolic dysfunction is a common finding in patients with systolic heart failure (HF). Severe diastolic dysfunction, which is defined as LV restrictive filling pattern (RFP), is associated with more severe HF, increased sympathetic activity and reduced exercise capacity. It has also been shown to be a predictor of lower survival rate in patients with HF.. To evaluate associations between LV diastolic RFP and BNP levels, systolic pulmonary pressure and exercise capacity in patients with clinically stable HF.. In 56 patients with HF and low LVEF a standard echocardiographic study and cardiopulmonary exercise test were performed. Levels of BNP using RIA method were also measured.. Restrictive filling pattern (E/A >2 or 1< E/A <2 and DTE < or =130 ms) was diagnosed in 26 patients. The RFP group showed increased levels of BNP (90.6+/-66 vs. 50.4+/-61 pg/ml; p=0.003), significantly reduced peak VO2 (15.4+/-4.1 vs. 17.8+/-4.9 ml/kg/min; p=0.046), increased VE/VCO2 slope (36.3+/-5.9 vs. 31.9+/-6.3; p=0.01), and elevated PASP (pulmonary artery systolic pressure measured by echo-Doppler) (49.3+/-13.8 vs. 37.2+/-12.6 mmHg; p=0.02). Prevalence of pulmonary hypertension was significantly higher in the RFP group. A significant correlation between DTE and peak VO2 (r=0.28; p=0.02) and inverse correlations between DTE and BNP levels (r=-048; p=0.003), VE/VCO2 slope (r=-0.35; p=0.02) and PASP (r=-0.39; p=0.03) were found. In logistic regression analysis only RFP was independently associated with pulmonary hypertension.. The restrictive filling pattern is an independent predictor of pulmonary hypertension and is associated with increased BNP levels and worse result of cardiopulmonary exercise test.

Topics: Adult; Diastole; Echocardiography; Exercise Test; Exercise Tolerance; Female; Heart Failure; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Stroke Volume; Ventricular Dysfunction, Left

Severe pulmonary hypertension (PAH) leads to right ventricular dysfunction and is associated with different atrial arrhythmias. In PAH patients, the echocardiographic Tei-index is used for monitoring right heart function. The P-wave signal-averaged ECG (SA-ECG) has been shown to have a potential role in identifying patients at risk of developing paroxysmal atrial fibrillation and those likely to change from paroxysmal to chronic atrial fibrillation. The aim of the present study was to define the correlation of the Tei-Index with parameters of P-wave triggered and bidirectional P-wave SA-ECG. A total of 18 patients (14 men, 4 women) with normal sinus rhythm and a mean age of 67+/-10 years (BMI 27.6+/-5.1 kg/m2) were included into the study. Right ventricular (RV) Tei-index was calculated from the sum of isovolumetric contraction time and relaxation time divided by ejection time. Furthermore, P-wave triggered P-wave signal averaged ECG was performed from an X, Y, and Z lead system. The results show that there was a statistically significant correlation between Tei-index and filtered P-wave duration (r=0.53; P=0.023). Teiindex did not correlate with the root mean square voltage of the last 20 ms of the P wave (r=-0.16; P=0.52). In conclusion, a correlation of RV Tei index with P-wave duration indicates that this echocardiographic measurement is not only a marker of right heart function, but also an indicator of electrical instability that could be useful to detect patients at risk for atrial arrhythmias.

Topics: Aged; Data Interpretation, Statistical; Echocardiography; Electrocardiography; Female; Heart; Heart Atria; Humans; Hypertension, Pulmonary; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Ventricular Dysfunction, Right

We describe two systemic sclerosis (SSc) patients with isolated pulmonary arterial hypertension (PAH) who were given treatment with 50 mg oral sildenafil per day. We evaluated the efficacy of oral sildenafil for isolated PAH in SSc patients by direct assessment with cardiac catheterization before and 6 months after the initiation of sildenafil. Right-heart catheterization demonstrated decreased mean pulmonary artery pressure, decreased pulmonary vascular resistance, and increased cardiac output after treatment with sildenafil. Brain natriuretic peptide levels were gradually decreased. The 6-min walking distance was greatly extended. Moreover, the physical conditions of both patients were much improved. We recognized no adverse events. We propose that oral sildenafil may be beneficial as a selective pulmonary vasodilator and as long-term treatment in SSc patients with isolated PAH.

Topics: Female; Hemodynamics; Humans; Hypertension, Pulmonary; Middle Aged; Natriuretic Peptide, Brain; Piperazines; Purines; Scleroderma, Systemic; Sildenafil Citrate; Sulfones; Vasodilator Agents

A pulsatile secretory pattern is assumed to improve hormonal efficiency. We examined the short-term time courses of circulating atrial (ANP) and brain natriuretic peptides (BNP) in patients with pulmonary hypertension (PH) and reduced renal efficiency of ANP-BNP, reflected by low natriuresis/ANP or BNP ratios. Compared to controls, we observed a persistence of ANP and BNP pulsatility in PH patients with a similar periodicity of 20min. Pulse amplitude increased proportionally to the rise in mean plasma level observed in patients (around 27%). In PH patients, the decrease in ANP-BNP renal efficiency is not attributable to a loss of the rhythmic pulsatility of these hormones.

Topics: Cardiac Catheterization; Humans; Hypertension, Pulmonary; Kidney; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptides; Periodicity; Time Factors

The detection of pulmonary hypertension in patients with chronic lung disease has prognostic implications. The brain natriuretic peptide (BNP) has been suggested as a noninvasive marker for the presence and severity of pulmonary hypertension.. We evaluated circulating BNP levels as a parameter for the presence and severity of pulmonary hypertension in patients with chronic lung disease.. BNP levels were measured in 176 consecutive patients with various pulmonary diseases. Right heart catheterization, lung functional testing, and a 6-min walk test were performed. The mean follow-up time was nearly 1 yr.. Significant pulmonary hypertension (mean pulmonary artery pressure > 35 mm Hg) was diagnosed in more than one-fourth of patients and led to decreased exercise tolerance and life expectancy. Elevated BNP concentrations identified significant pulmonary hypertension with a sensitivity of 0.85 and specificity of 0.88 and predicted mortality. Moreover, BNP served as a risk factor of death independent of lung functional impairment or hypoxemia in uni- and multivariate analysis.. We suggest BNP as a prognostic marker and as screening parameter for significant pulmonary hypertension in chronic lung disease.

Topics: Adult; Biomarkers; Cardiac Catheterization; Cardiac Output; Disease Progression; Exercise Test; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Plethysmography; Prognosis; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulmonary Wedge Pressure; Severity of Illness Index; Spirometry; Survival Rate

A term (39-wk-old) male neonate exhibited respiratory distress and anuria within 2 days of birth. The patient was diagnosed with pulmonary hypertension, polycystic kidney disease, and heart failure; his initial B-type natriuretic peptide concentration was 2460 pg/ml. After minimal response to loop diuretics, the patient was given an infusion of nesiritide 0.01 microg/kg/minute, with no loading dose. Urine output increased over 400%, and cardiac function improved. Nesiritide was titrated to 0.03 microg/kg/minute with no hypotension, decreased renal function, or adverse cardiac sequelae over the next 6 days. No subsequent changes in cardiac function occurred during the infant's stay in a progressive care unit, but he died at age 5.5 months due to sepsis. This case report demonstrates the successful first use of nesiritide therapy in a neonate with renal disease. Further studies are warranted to evaluate the safety and administration of this agent in the neonatal patient population.

Topics: Blood Urea Nitrogen; Diuretics; Electrocardiography; Fatal Outcome; Heart Defects, Congenital; Heart Failure; Hemodynamics; Humans; Hypertension, Pulmonary; Infant, Newborn; Male; Natriuretic Agents; Natriuretic Peptide, Brain; Polycystic Kidney Diseases

Brain natriuretic peptide (BNP) blunts hypoxic pulmonary hypertension in animal models, but its acute hemodynamic effects in patients with pulmonary arterial hypertension (PAH) are not known. The aim of this study was to determine if human B-type natriuretic peptide is a safe and efficacious pulmonary vasodilator in patients with PAH and if the pulmonary hemodynamic effects are potentiated by phosphodiesterase inhibition.. Open-label study.. Medical ICUs of three tertiary care hospitals in New England.. Thirteen consecutive adult patients undergoing right-heart catheterization and a pulmonary vasodilator trial for the initial evaluation of PAH.. Patients were administered inhaled nitric oxide (iNO), i.v. epoprostenol, and a 3-h infusion of BNP alone and 1 h after an oral dose of the phosphodiesterase-5 inhibitor sildenafil.. iNO and sildenafil alone decreased mean pulmonary artery pressure (mPAP) without a significant fall in pulmonary vascular resistance (PVR). Epoprostenol decreased both mPAP and PVR. BNP alone had no significant effect on pulmonary hemodynamics, but the combination of sildenafil plus BNP decreased mPAP and PVR for up to 6 h after stopping BNP. The decrease in mPAP with sildenafil plus BNP (+/- SE) was greater than after 1 h of sildenafil alone (44.6 +/- 3.8 to 40.6 +/- 3.9 mm Hg, p = 0.027). An acute vasodilator response, defined as a decrease in mPAP > 10 mm Hg and end mPAP < 40 mm Hg, was seen in 0 of 8 patients with iNO, 1 of 13 patients with epoprostenol, 0 of 13 patients with BNP, and 4 of 12 patients with sildenafil plus BNP. BNP decreased mean systemic arterial pressure (5.6 +/- 2.8 mm Hg) but had no effect on cardiac output or systemic vascular resistance.. A 3-h BNP infusion does not significantly improve pulmonary hemodynamics in most patients with PAH but is well tolerated and augments the acute pulmonary vasodilator effect of sildenafil.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aged; Aged, 80 and over; Blood Pressure; Drug Synergism; Drug Therapy, Combination; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Male; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Pulmonary Circulation; Purines; Sildenafil Citrate; Sulfones; Vascular Resistance; Vasodilator Agents

Primary pulmonary hypertension (PPH) is a progressive disease leading to right heart failure and death. Right heart catherization and maximal or submaximal tests are employed to assess the course of the disease. A neurohormonal parameter such as pro-brain natriuretic peptide (BNP) would be helpful in the assessment of these patients.. To study the correlation of BNP with functional status and non-invasive hemodynamic determinations in patients with PPH.. Twelve patients (mean age: 48 years; 58% female) were evaluated with 6 minutes walk distance test (6-min WT), plasma BNP, systolic pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR) and cardiac output (CO) determined by echocardiogram. Plasma BNP levels were compared with normal subjects.. BNP levels were increased in PPH patients (1270+/-547 vs 48+/-8 pg/ml, p-value <0.01). Mean PAPs was 82+/-27 mmHg and the mean distance walked in 6 minutes was 407+/-113 meters. BNP levels were positively correlated with PVR (r=0.58, p-value=0.006) and negatively correlated with 6-min WT (r=-0.83, p-value <0.001). No correlation was found between BNP levels, PAPs and CO.. In PPH patients, BNP levels are increased and correlate with functional class and PVR. Follow-up studies are needed to evaluate the role of BNP as a marker of progression and therapeutic response in PPH patients.

Topics: Biomarkers; Blood Pressure; Cardiac Output; Case-Control Studies; Echocardiography; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Vascular Resistance; Walking

In monocrotaline (MCT)-induced pulmonary hypertension (PH), only the right ventricle (RV) endures overload, but both ventricles are exposed to enhanced neuroendocrine stimulation. To assess whether in long-standing PH the left ventricular (LV) myocardium molecular/contractile phenotype can be disturbed, we evaluated myocardial function, histology, and gene expression of autocrine/paracrine systems in rats with severe PH 6 wk after subcutaneous injection of 60 mg/kg MCT. The overloaded RV underwent myocardial hypertrophy (P < 0.001) and fibrosis (P = 0.014) as well as increased expression of angiotensin-converting enzyme (ACE) (8-fold; P < 0.001), endothelin-1 (ET-1) (6-fold; P < 0.001), and type B natriuretic peptide (BNP) (15-fold; P < 0.001). Despite the similar upregulation of ET-1 (8-fold; P < 0.001) and overexpression of ACE (4-fold; P < 0.001) without BNP elevation, the nonoverloaded LV myocardium was neither hypertrophic nor fibrotic. LV indexes of contractility (P < 0.001) and relaxation (P = 0.03) were abnormal, however, and LV muscle strips from MCT-treated compared with sham rats presented negative (P = 0.003) force-frequency relationships (FFR). Despite higher ET-1 production, BQ-123 (ET(A) antagonist) did not alter LV MCT-treated muscle strip contractility distinctly (P = 0.005) from the negative inotropic effect exerted on shams. Chronic daily therapy with 250 mg/kg bosentan (dual endothelin receptor antagonist) after MCT injection not only attenuated RV hypertrophy and local neuroendocrine activation but also completely reverted FFR of LV muscle strips to positive values. In conclusion, the LV myocardium is altered in advanced MCT-induced PH, undergoing neuroendocrine activation and contractile dysfunction in the absence of hypertrophy or fibrosis. Neuroendocrine mediators, particularly ET-1, may participate in this functional deterioration.

Topics: Angiotensinogen; Animals; Antihypertensive Agents; Bosentan; Cytochrome P-450 CYP11B2; Endothelin-1; Gene Expression Regulation; Heart Ventricles; Hemodynamics; Hypertension, Pulmonary; Male; Monocrotaline; Myocardial Contraction; Natriuretic Peptide, Brain; Neurotransmitter Agents; Peptides, Cyclic; Peptidyl-Dipeptidase A; Rats; Rats, Wistar; RNA, Messenger; Sulfonamides; Ventricular Function; Ventricular Remodeling

The aims of this study were to evaluate the diagnostic value and to explore the prognostic value of N-terminal brain natriuretic peptide (N-TproBNP) in patients with systemic sclerosis (SSc) both with and without pulmonary arterial hypertension (PAH).. N-TproBNP, six-minute walk distance (SMWD), haemodynamics (at right heart catheterization) or tricuspid gradient (by echocardiography), and survival were assessed in 109 patients with SSc. The study population included 68 individuals with PAH [mean pulmonary artery pressure (PAP) >25 mmHg and pulmonary capillary wedge pressure <15 mmHg] and 41 individuals without PAH. In patients with PAH, the prognostic value of baseline and change in WHO functional class, N-TproBNP levels, and SMWD were compared using Kaplan-Meier survival curves and Cox proportional hazard analysis. The mean duration of follow-up was 10 months (range 1-18 months). One year survival in patients with normal PAP was 100% when compared with 83.5% in those with SSc-PAH (P < 0.05). The patients without PAH had a mean N-TproBNP level of 139 pg/mL (SD 151); those with SSc-PAH had a significantly higher mean N-TproBNP level of 1474 pg/mL (SD 2642) (P = 0.0002). Among patients with PAH for every order of magnitude increase in N-TproBNP level there was a four-fold increased risk of death (P = 0.002 for baseline level and P = 0.006 for follow-up level). Baseline N-TproBNP levels were correlated positively with mean PAP (r = 0.62; P < 0.0001), pulmonary vascular resistance (PVR) (r = 0.81; P < 0.0001), and inversely with SMWD (r = -0.46; P < 0.0001). Among patients with SSc-PAH, 13 patients (19%) were in WHO functional classes II and had mean N-TproBNP levels of 325 pg/mL (SD 388). Fifty-three patients (78%) were in WHO classes III and IV and had significantly higher mean N-TproBNP levels of 1677 pg/mL (SD 2835) (P = 0.02). At an N-TproBNP level of 395 pg/mL, the sensitivity and specificity for predicting the presence of SSc-PAH were 56 and 95% respectively.. Raised N-TproBNP levels are directly related to the severity of PAH. In screening programs, SSc patients with an N-TproBNP in excess of 395 pg/mL have a very high probability of having pulmonary hypertension. Baseline and serial changes in N-TproBNP levels are highly predictive of survival. A 10-fold increase in N-TproBNP level on therapy is associated with a greater than three-fold increase in mortality, and may indicate therapeutic failure.

Topics: Echocardiography; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Scleroderma, Systemic; Survival Analysis; Ventricular Function, Right

Baseline prognostic assessment in patients with pulmonary hypertension (PH) may help in the selection of treatment. High plasma levels of natriuretic peptide type B have been reported in patients with right ventricular (RV) dysfunction and suggest poor prognosis in patients with idiopathic pulmonary arterial hypertension (IPAH). We prospectively assessed the correlation of N-terminal brain natriuretic peptide (NT-proBNP) with echocardiographic and hemodynamic indexes of RV function as well as with baseline functional status and long-term survival of PH patients.. Fifty-five consecutive patients with a mean (+/- SD) age of 41 +/- 15 years and severe PH (including 36 patients with IPAH) were followed up for up to 36 months. Serum samples for NT-proBNP were secured, and 6-min walk test (6 MWT), RV catheterization, and echocardiography were all performed on the same day, before the introduction of targeted treatment.. The median baseline serum NT-proBNP concentration was 1,674 pg/mL (range, 51 to 10,951 pg/mL). NT-proBNP concentration correlated with 6MWT distance (r = 0.6; p < 0.001), cardiac index, pulmonary vascular resistance, and right atrial pressure (RAP), but not with pulmonary arterial pressure. NT-proBNP levels were also related to the ratio of the diastolic area of the RV and the LV, and to pericardial effusion during echocardiography. Receiver operating characteristic analysis identified > or = 1,400 pg/mL as the best NT-proBNP threshold predicting fatal outcome for the entire study group as well as for IPAH patients (sensitivity, 88% and 100%, respectively; specificity, 53% and 56%, respectively). In multivariate analysis, NT-proBNP, troponin T, and RAP were identified as independent factors for poor prognosis for the entire study group, while only NT-proBNP and RAP were identified as markers for poor prognosis in the IPAH subgroup.. NT-proBNP level is related to the right heart morphology and dysfunction in PH patients. A serum NT-proBNP level of > or = 1,400 pg/mL was found to be useful in identifying patients with poor long-term prognosis both in the whole studied group and in the IPAH subgroup.

Topics: Adult; Biomarkers; Cardiac Catheterization; Echocardiography; Female; Humans; Hypertension, Pulmonary; Immunoassay; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Pulmonary Wedge Pressure; Retrospective Studies; Severity of Illness Index; Ventricular Dysfunction, Right; Ventricular Pressure

Thirty percent of patients with sickle cell disease (SCD) develop pulmonary hypertension, a major risk factor for death in this population. A validated blood biomarker of pulmonary hypertension in SCD could provide important prognostic and diagnostic information and allow the exploration of the prevalence of pulmonary hypertension in participants in the 1996 Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) Patients' Follow-up Study. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) provide such information in patients with idiopathic pulmonary arterial hypertension.. To determine the relationship between NT-proBNP levels and severity of pulmonary hypertension and prospective mortality in patients with SCD.. NT-proBNP levels were measured in 230 participants in the National Institutes of Health (NIH) Sickle Cell Disease-Pulmonary Hypertension Screening Study (enrollment between February 2001 and March 2005) and in 121 samples from patients enrolled starting in 1996 in the MSH Patients' Follow-up Study. A threshold level predictive of high pulmonary artery pressure and mortality was identified in the NIH Sickle Cell Disease-Pulmonary Hypertension Screening Study and used to define an a priori analytical plan to determine the prevalence and associated mortality of pulmonary hypertension in the MSH follow-up study.. Severity of pulmonary hypertension and risk of all-cause mortality.. NT-proBNP levels were higher in patients with sickle cell pulmonary hypertension and correlated directly with tricuspid regurgitant jet velocity in the NIH cohort (R = 0.50, P<.001). An NT-proBNP level of 160 pg/mL or greater had a 78% positive predictive value for the diagnosis of pulmonary hypertension and was an independent predictor of mortality (21 deaths at 31 months' median follow-up; risk ratio, 5.1; 95% confidence interval, 2.1-12.5; P<.001; 19.5% absolute increase in risk of death). In the MSH cohort, 30% of patients had an NT-proBNP level of 160 pg/mL or greater. An NT-proBNP level of 160 pg/mL or greater in the MSH cohort was independently associated with mortality by Cox proportional hazards regression analysis (24 deaths at 47 months' median follow-up; risk ratio, 2.87; 95% confidence interval, 1.2-6.6; P = .02; 11.9% absolute increase in risk of death).. Pulmonary hypertension, as indicated by an NT-proBNP level of 160 pg/mL or greater, was very common in patients in the NIH study and in the MSH cohort. The MSH analysis suggests that rates of vaso-occlusive pain episodes in these patients were unrelated to risk of death; this risk was largely determined by occult hemolytic anemia-associated pulmonary hypertension.

Topics: Adult; Anemia, Sickle Cell; Female; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Proportional Hazards Models; Risk; Survival Analysis

N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) is well established as a predictor of prognosis in patients with left ventricular dysfunction. Although a similar prognostic significance has been suggested in 1 study of right ventricular failure and idiopathic pulmonary arterial hypertension, NT-pro-BNP has not been assessed as a marker of disease severity in a more heterogenous group of patients with chronic precapillary pulmonary hypertension (PH). Hence, this study assessed plasma NT-pro-BNP and other clinical variables in 61 consecutively recruited patients with various forms of chronic precapillary PH. Right-sided cardiac catheterization and cardiopulmonary exercise testing were performed at baseline, and the prognostic significance of NT-pro-BNP was investigated with a mean follow-up of 25 months. Compared with age-matched controls (n = 10), plasma NT-pro-BNP was significantly greater in those with idiopathic pulmonary arterial hypertension (n = 16), chronic precapillary PH associated with other diseases (n = 26), and chronic thromboembolic disease (n = 19) and was correlated with hemodynamic variables and functional capacity. In 17 medically treated patients, the significant decrease in NT-pro-BNP levels correlated with improved hemodynamics. During follow-up, 15 patients died from cardiopulmonary causes. Baseline NT-pro-BNP was an independent predictor of mortality. Kaplan-Meier survival analysis according to the median value of NT-pro-BNP (168 pmol/L) demonstrated a significantly higher mortality rate in those with supramedian values than in those with low plasma levels (p = 0.010). In conclusion, these findings suggest that in a heterogenous group of patients with chronic precapillary PH, plasma NT-pro-BNP can be used to determine the clinical severity of disease and is independently associated with long-term mortality.

Topics: Biomarkers; Cardiac Catheterization; Chronic Disease; Exercise Test; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Pulmonary Wedge Pressure; ROC Curve; Severity of Illness Index; Survival Rate; Time Factors

Left ventricular remodeling might be involved in the pathophysiology of right ventricular hypertrophy/failure due to pulmonary arterial hypertension (PAH), while the left ventricle is considered not under pressure/volume overload.. Rats with monocrotaline-induced PAH were used in the present study to examine whether upregulated neurohumoral factors may induce left ventricular (LV) remodeling and(/or) contribute to prognosis. Morphological analysis revealed a significant increase in the weight of the free walls of both ventricles and the interventricular septum, indicating biventricular hypertrophy, although systemic blood pressure was not elevated. RNase protection assay demonstrated the activation of a fetal gene program in the cardiac muscle of the left and right ventricular free walls. Similar activation of the fetal gene program was observed in the LV of rats continuously infused with angiotensin (AT) II, although this was not the case for rats infused with isoproterenol. Measured plasma levels of ATII, noradrenaline, and brain natriuretic peptide (BNP) were all significantly elevated in the PAH rats. Furthermore, the plasma BNP level positively correlated with the ratio of heart weight to body weight and the plasma level of ATII. Not right but LV hypertrophy was significantly reduced by treatment with an AT II type 1 receptor blocker, valsartan, whereas the effect of an adrenergic alpha1 and beta1,2 blocker, carvedilol, was borderline. Survival rate in the PAH rats was significantly improved when they were treated with valsartan or carvedilol.. Upregulated neurohumoral factors seem to play an important role in LV remodeling without mechanical overload, and are associated with impairment of prognosis in rats with PAH.

Topics: Angiotensin II; Animals; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Male; Monocrotaline; Natriuretic Peptide, Brain; Norepinephrine; Prognosis; Rats; Rats, Wistar; Up-Regulation; Ventricular Remodeling

Pulmonary hypertension (PH) is characterized by decreased pulmonary vascular expression of nitric oxide (NOx), a vasodilator that increases levels of smooth muscle cyclic guanosine monophosphate (cGMP). This study investigated mechanisms by which the vasodilator B-type natriuretic peptide (BNP) affects the systemic and pulmonary vasculature in PH patients.. Twenty PH patients with mean pulmonary artery (PA) pressure > 25 mm Hg were enrolled. Ten had precapillary (pulmonary capillary wedge pressure [PCWP] < or = 15 mm Hg) and 10 had postcapillary (PCWP > 15 mm Hg) PH. Right heart catheterization was performed before and 30 minutes after intravenous nesiritide infusion. NOx and cGMP levels from the PA and systemic (AO) arteries were obtained before and after nesiritide infusion. The postcapillary PH patients demonstrated significantly reduced pulmonary vascular resistance after nesiritide; there was no change in the precapillary PH cohort. NOx levels increased significantly in both AO (P < .0001) and PA (P = .0093), as did cGMP levels (P < .0001). There was a higher increase in NOx levels from the pulmonary arteries in precapillary PH patients compared to postcapillary PH patients (P = .020).. In PH patients, nesiritide infusion significantly increases NOx levels, suggesting a novel mechanism for its vasodilatory effects. These responses may differ between pre- and postcapillary PH patients.

Topics: Adult; Aged; Arteries; Capillaries; Cohort Studies; Cyclic GMP; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Nitric Oxide; Prospective Studies; Pulmonary Artery; Pulmonary Wedge Pressure; Vascular Resistance; Vasodilator Agents

The aim of the current study was to investigate whether alterations in N-terminal pro brain natriuretic peptide (NT-proBNP) reflect changes in right ventricular structure and function in pulmonary hypertension patients during treatment. The study consisted of 30 pulmonary hypertension patients; 15 newly diagnosed and 15 on long-term treatment. NT-proBNP, right heart catheterisation and cardiac magnetic resonance imaging measurements were performed, at baseline and follow-up. There were no significant differences between newly diagnosed patients and those on treatment at baseline or follow-up with respect to NT-proBNP, haemodynamics and right ventricular parameters. Relative changes in NT-proBNP during treatment were correlated to the relative changes in right ventricular end-diastolic volume index (r = 0.59), right ventricular mass index (r = 0.62) and right ventricular ejection fraction (r = -0.81). N-terminal pro brain natriuretic peptide measurements reflect changes in magnetic resonance imaging-measured right ventricular structure and function in pulmonary hypertension patients. An increase in N-terminal pro brain natriuretic peptide over time reflects right ventricular dilatation concomitant to hypertrophy and deterioration of systolic function.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cardiac Catheterization; Female; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Ventricular Dysfunction, Right

Topics: Biomarkers; Humans; Hypertension, Pulmonary; Models, Theoretical; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Regression Analysis; Sensitivity and Specificity

Topics: Female; Humans; Hypertension, Pulmonary; Male; Natriuretic Peptide, Brain; Peptide Fragments; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents; Ventricular Remodeling

We measured plasma BNP and hANP levels and studied the relationship to echocardiographic findings in 49 patients who visited or admitted in our hospital due to dyspnea (25 with chronic obstructive pulmonary disease (COPD), 8 with interstitial pneumonia, 16 with sequelae of tuberculosis). The age in the interstitial pneumonia group was lower and the arterial blood partial pressure of CO2 was higher in the sequelae of tuberculosis group. Plasma BNP and hANP levels were similar in the three groups. Plasma BNP level did not correlate with the pressure gradient measured from tricuspid valve regurgitation. Some patients had pulmonary hypertension despite having low plasma BNP levels. Hypoxemia was more severe in the higher BNP level group than in the lower BNP level group. Plasma BNP levels did not reflect pulmonary hypertension unless these was left ventricular failure or valvular diseases in these groups.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Disease, Chronic Obstructive; Respiration Disorders

To evaluate the longitudinal development of the tricuspid gradient (TG) for screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc).. Doppler echocardiography was performed 506 times in order to estimate TG in 227 consecutive patients with SSc. The value of biochemical markers for predicting TG levels and development was assessed through analyses of pro-brain natriuretic peptide (proBNP), calcitonin-gene related peptide, thrombomodulin and von Willebrand factor in 76 patients with a borderline increase in TG, defined as TG 24-38 mmHg, and for the purpose of comparison also in 10 patients with a normal TG (< 23 mmHg) and in 10 patients with increased TG (TG > 38 mmHg).. TG > 23 mmHg was found in 102 patients (44.9%) at the first assessment point and in 139 patients (61.2%) respectively, cumulatively at follow-up. TG values > 33 mmHg were measured in 24 patients (10.6%) initially and in 38 patients (16.7%) cumulatively in a subsequent assessment. Age and the presence of interstitial lung disease (ILD) were associated with more frequent occurrence of TG > 23 and > 33 mmHg initially and at follow-up, but were not associated with progression rate. The change in TG (mean +/- S.D.) was 1.34 +/- 4.55 mmHg/yr. ProBNP correlated to TG.. An increased TG, indicating possible PAH, is common and progressive in SSc. Age and ILD increase the risk of increased TG. Patients with or without ILD have similar progression of TG. ProBNP has potential as an adjunct to TG in selecting patients eligible for invasive treatment.

Topics: Age Factors; Blood Pressure; Calcitonin Gene-Related Peptide; Carbon Monoxide; Echocardiography, Doppler; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Middle Aged; Natriuretic Peptide, Brain; Scleroderma, Systemic; Thrombomodulin; Tricuspid Valve; Tricuspid Valve Insufficiency; von Willebrand Factor

The impact of adding nesiritide to standard therapy and positive inotropic agents in patients with end-stage heart failure and secondary pulmonary hypertension (PH) was studied.. Patients included in this retrospective study were 18 years of age or older, admitted to the hospital with PH secondary to end-stage heart failure (New York Heart Association functional class IV), had received a pulmonary artery catheter, had been treated with nesiritide because of inadequate hemodynamic response to previous therapy (pulmonary capillary wedge pressure [PCWP], >18 mm Hg), and had shown minimal symptomatic benefit from standard heart-failure therapy, continuous infusions of loop diuretics, and positive inotropic agents (milrinone or dobutamine or both). The primary endpoint was change in PCWP. Secondary endpoints included change in mean pulmonary artery pressure (MPAP), change in cardiac index (CI), change in mean arterial pressure (MAP), change in serum creatinine (SCr) concentration, and occurrence of symptomatic hypotension.. The study included 33 patients. Mean PCWP was reduced by 31.1% with the addition of nesiritide to previous therapy (p < 0.0001). Significant improvements in other hemodynamic variables, including MPAP (15.6% reduction) and CI (13.0% increase), were also observed. MAP was reduced significantly (by 15.2%), but SCr concentration did not change. There were five episodes of symptomatic hypotension. All patients exhibited relief of dyspnea symptoms.. The addition of nesiritide to standard therapy and positive inotropic agents improved hemodynamic measures and clinical symptoms in patients with end-stage heart failure and secondary pulmonary hypertension.

Topics: Adult; Blood Pressure; Female; Heart Failure; Humans; Hypertension, Pulmonary; Male; Natriuretic Agents; Natriuretic Peptide, Brain; Pulmonary Wedge Pressure; Retrospective Studies

Topics: Antihypertensive Agents; Epoprostenol; Humans; Hypertension, Pulmonary; Natriuretic Agents; Natriuretic Peptide, Brain; Treatment Outcome

Severe pulmonary hypertension (PH) and increased pulmonary vascular resistance (PVR) are important risk factors that predict early postoperative mortality after orthotopic heart transplantation. The aim of our study was to determine the value of B-type natriuretic peptide (BNP) and big endothelin-1 (big ET1) for prediction of severe PH in heart transplant candidates.. The study population included 43 potential heart transplant candidates (38 males, mean age 52 +/- 7 years). All underwent repeated right-heart catheterizations (2-5 studies) at an interval of 3-4 months, giving a total of 124 examinations, associated with blood sampling for BNP and big ET1 analysis. Severe PH was defined as the mean pulmonary artery pressure (MPAP) > 40 mmHg.. Significantly high PVR (PVR > 3.0 Wood units and TPG > 15 mmHg) was noted on 12 occasions in 10 patients; always in the presence of severe PH. Low BNP levels (<67 pg/ml) ruled out the presence of severe PH with a 100% sensitivity, however, with a low specificity (34%). An increase in plasma BNP > 30 pg/ml (>40% of initial value) in subjects with a previous MPAP< or =40 mmHg detected development of severe PH with a 100% sensitivity and an 80-88% specificity. As a total of 58% of patients presented repeatedly with MPAP< or =40 mmHg, serial BNP testing could reduce the need for hemodynamic studies in this subgroup down to 12-20%.. Serial BNP testing in hemodynamically stable heart transplant candidates with MPAP< or =40 mmHg allows reliable detection of development of severe PH, and may significantly reduce the need for repeated right-heart catheterizations in these patients.

Topics: Adult; Aged; Biomarkers; Cardiac Catheterization; Endothelin-1; Female; Heart Transplantation; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Pulmonary Wedge Pressure; Radioimmunoassay; Retrospective Studies; Severity of Illness Index

Nesiritide is a recombinant brain-type natriuretic peptide (BNP), which decreases pulmonary arterial (PA) pressures and myocardial oxygen consumption while increasing coronary flow and urine output. Mitral valve (MV) surgery in patients with severe mitral regurgitation (MR), impaired left ventricular function, and pulmonary hypertension is associated with a high operative mortality. We hypothesized that the perioperative use of Nesiritide is safe, and may improve surgical outcomes.. From May 2003 to August 2004, 14 patients (11 male, 3 female; mean age, 64 years [23-87 years]; mean systolic PA, 63 mm Hg [48-94 mm Hg]; mean ejection fraction, 36% [10-50%]), undergoing MV surgery (10 repairs, 2 replacements, and 2 rereplacements) for severe MR, were treated for a median of 24 hours (13-55 hours) preoperatively with intravenous Nesiritide. Expected mortality by EuroSCORE was 26% (7.8-59%) (5 reoperations). Concomitant procedures included tricuspid valve repair (n = 7), coronary artery bypass grafting (n = 5), and left atrial maze procedure (n = 3). Eleven patients received Nesiritide postoperatively during a mean duration of 22 hours (2-80 hours).. Operative mortality was 0%. Prior to surgery after BNP treatment, mean systolic PA pressure dropped to 39 mm Hg (p = 0.0003), pulmonary capillary wedge pressure to 15 mm Hg (p = 0.001), central venous pressure to 6 mm Hg (p = 0.002), and weight by 3.7 kg (p = 0.006). Postoperative median ventilation time was 14 hours (4-48 hours). All other major hemodynamic parameters (systemic blood pressure, heart rate, and cardiac output) remained constant. The treatment was well-tolerated in all patients.. Perioperative use of Nesiritide is safe, and may contribute to improved early outcomes in high-risk patients undergoing MV surgery. This may be due to improved ventricular loading conditions (decreased PA pressures, more effective diuresis) and/or a direct myocardial effect of BNP. Further prospective evaluation of the role of BNP in cardiac surgery is warranted.

Topics: Adult; Aged; Aged, 80 and over; Cardiac Surgical Procedures; Cardiovascular Agents; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mitral Valve; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Prospective Studies; Ventricular Dysfunction, Left

Nesiritide is effective in the treatment of decompensated heart failure (HF). We evaluated the acute hemodynamic effects of nesiritide, a recombinant B-type natriuretic peptide, in patients with HF and pulmonary hypertension (PH).. Twenty patients with HF and PH (mean pulmonary arterial [PA] pressure >25 mm Hg) were enrolled: 10 with postpulmonary capillary wedge (PCW) >15 mm Hg and 10 with precapillary PH (PCW) < or =15. The pulmonary and systemic hemodynamics were determined by right heart catheterization at baseline and at 15 and 30 minutes after an intravenous nesiritide infusion (2 mcg/kg bolus and 0.01 mcg.kg.min). For the patients with postcapillary PH, the mean left ventricular ejection fraction was 28 +/- 15%. After the 30-minute nesiritide infusion, right atrial (RA) pressure decreased 48% (P < .0001), mean PA pressure decreased 29% (P < .0001), PCW pressure decreased 40% (P < .0001), cardiac index (CI) increased 35% (P = .009), pulmonary vascular resistance index (PVRI) decreased 35% (P = .01), and arteriovenous oxygen difference (AVDO(2)) decreased 27% (P = .0003). For precapillary PH patients, there was no change in RA, PA, or PCW pressure, nor any change in CI, PVRI, or AVDO(2).. Nesiritide acutely and significantly reduced PA pressure, PVRI, and biventricular filling pressures in patients with postcapillary PH. However, for patients with precapillary PH, nesiritide had no significant acute hemodynamic effect on the pulmonary hemodynamics. The lack of acute beneficial effects of nesiritide in patients with advanced precapillary PH may be related to their relatively fixed remodeling of the pulmonary vasculature.

Topics: Adult; Aged; Biomarkers; Female; Heart Failure; Heart Rate; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Male; Middle Aged; Myocardial Contraction; Natriuretic Agents; Natriuretic Peptide, Brain; Prospective Studies; Pulmonary Wedge Pressure; Stroke Volume; Treatment Outcome; Vascular Resistance; Ventricular Dysfunction, Left

Pulmonary arterial hypertension complicated by decompensated cor pulmonale is a challenging clinical problem with few effective therapeutic options. B-type natriuretic peptide is a pluripotent hormone that promotes diuresis and natriuresis, vasodilates systemic and pulmonary vessels, and reduces circulating levels of endothelin and aldosterone. It may represent a possible therapeutic strategy for decompensated cor pulmonale in the same manner that it is used to treat decompensated left heart failure. The authors report their experience with B-type natriuretic peptide as adjunctive therapy for pulmonary arterial hypertension complicated by decompensated cor pulmonale. A detailed case report is presented followed by the evaluation of a series of 11 cases occurring in eight patients from December 2002 through April 2004.

Topics: Adult; Aged; Blood Pressure; Body Weight; Cardiac Output; Clinical Nursing Research; Disease Progression; Drug Monitoring; Dyspnea; Echocardiography, Transesophageal; Female; Heart Failure; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Male; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Pulmonary Heart Disease; Pulmonary Wedge Pressure; Severity of Illness Index; Treatment Outcome

We established a rat chronic alveolar hypoxia in vivo model to evaluate the efficacy against hypoxic pulmonary hypertension of a new angiotensin II-receptor I blocker, olmesartan medoxomil. Three groups of rats were established: rats exposed for 2-6 weeks to 10% oxygen atmosphere in a normobaric chamber; hypoxic rats treated with olmesartan medoxomil oral administration (5 mg/day) every day; and control rats fed in a normoxic condition. After hypoxia treatment, the presence, etiology and severity of pulmonary hypertension, was echocardiographically evaluated, and expressions of brain natriuretic peptide (BNP), transforming growth factor (TGF-beta) and endothelin-1 genes measured by both immunohistochemical assay and real-time polymerase chain reaction. Olmesartan medoxomil significantly reduced the induction of hypoxic cor pulmonale not only on echocardiographical observations but also in BNP, TGF-beta and endothelin gene expressions in molecular studies. However, systolic blood pressure was independent of olmesartan medoxomil. The present study clearly indicates that the angiotensin II-type I-receptor blocker olmesartan medoxomil has significant efficacy for hypoxic cor pulmonale.

Topics: Administration, Oral; Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Collagen; Disease Models, Animal; Echocardiography; Endothelins; Heart; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Imidazoles; Lung; Male; Myocardium; Natriuretic Peptide, Brain; Olmesartan Medoxomil; Pulmonary Artery; Pulmonary Heart Disease; Rats; Rats, Wistar; RNA, Messenger; Tetrazoles; Transforming Growth Factor beta

Topics: Blood Pressure; Hemodynamics; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Piperazines; Pulmonary Artery; Purines; Sildenafil Citrate; Sulfones; Vascular Resistance; Vasodilator Agents

The aim of this study was to investigate the potential role of brain natriuretic peptide (BNP) levels in the assessment of functional status and right heart performance in primary pulmonary hypertension (PPH).. Primary pulmonary hypertension is a progressive disease leading to right heart failure and death. Right heart catheterization and maximal or submaximal exercise tests are employed to assess the course of the disease and the effect of therapeutic interventions. Additional noninvasive and reproducible parameters would be helpful to assess the status of patients with PPH. The natriuretic peptide system is up-regulated in PPH patients. Brain natriuretic peptide (BNP) is produced from the cardiac ventricles and elevated in PPH. The aim of our study was to evaluate the clinical significance of BNP in PPH patients.. Correlation analysis was performed for plasma BNP levels of 28 PPH patients and World Health Organization (WHO) functional class (WHO-class), distance walked in 6 min, peak oxygen uptake (peak Vo(2)), and oxygen pulse during spiroergometry and various hemodynamic parameters, including pulmonary vascular resistance (PVR), pulmonary artery pressure (PAP), right atrial pressure (RAP), and cardiac index.. The BNP levels were inversely correlated with the 6-min walk (r = -0.70; p < 0.001) and peak Vo(2) (r = -0.61; p < 0.01), and positive correlation was observed with WHO-class (r = 0.79; p < 0.001). Moreover, BNP levels were also correlated to PVR (r = 0.61; p < 0.01), PAP (r = 0.48; p < 0.05), and RAP (r = 0.78; p < 0.01), and were inversely related to cardiac index (r = -0.48; p < 0.05).. Our data suggest that plasma BNP levels are closely related to the functional impairment of PPH patients and parallel the extent of pulmonary hemodynamic changes and right heart failure. Serial measurements of plasma BNP concentrations may help improve the management of PPH patients.

Topics: Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Severity of Illness Index

We present the case of a patient with severe symptomatic pulmonary hypertension due to rheumatic mitral valve disease who was refractory to traditional therapies, including prostacyclin. Therapy with continuous nesiritide infusion resulted in significant and sustained decreases in pulmonary vascular resistance, an improvement in renal function, and the maintenance of euvolemia.

Topics: Female; Humans; Hypertension, Pulmonary; Middle Aged; Natriuretic Agents; Natriuretic Peptide, Brain; Treatment Outcome

Topics: Biomarkers; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Pulmonary Fibrosis; Sensitivity and Specificity

Endothelin-1 (ET-1) levels are elevated in congestive heart failure (CHF) in relation with the severity of pulmonary hypertension. We evaluated whether a reduced pulmonary ET-1 clearance could contribute to this elevation.. We determined pulmonary ET-1 clearance in 24 patients with CHF in relation with hemodynamics, plasma ET-1, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Pulmonary ET-1 extraction, measured by the single bolus indicator-dilution technique, was reduced to 32 +/- 14% in comparison to historic controls (47 +/- 7%). Plasma ET-1 clearance by the lungs (924 +/- 588 mL/min) was also much lower than in controls (1424 +/- 79 mL/min). Clearance correlated inversely with mean pulmonary artery pressure (PAP, r = -.47, P = .017) and pulmonary capillary wedge pressure (r = -.47, P = .017) and positively with the rate of left ventricular (LV) relaxation LV -dP/dt (r = .593, P = .004). After multivariate analysis, only mean PAP and LV -dP/dt were independently correlated with ET-1 clearance (r = -.40, P = .03, and r = .55, P = .005, respectively). Plasma ET-1 levels did not correlate with clearance (r = .038, P = .86), and there was no significant arteriovenous ET-1 gradient. There was a mild nonsignificant correlation between plasma ET-1 and pulmonary artery systolic pressure (r = .38, P = .06), but a strong correlation with right atrial pressure (r = .696, P < .0001) and NT-proBNP levels (r = .51, P = .001), which were maintained after multivariate linear regression (r = .60, P = .001, and r = .32, P = .04, respectively).. Pulmonary ET-1 clearance is reduced in CHF in relation with the severity of pulmonary hypertension. This reduced clearance does not significantly modulate plasma ET-1 levels. Whether this is only a marker of secondary pulmonary hypertension or could modulate pulmonary vascular tone will require further studies.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Endothelin-1; Female; Heart Failure; Humans; Hypertension, Pulmonary; Indicator Dilution Techniques; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; Pulmonary Circulation; Pulmonary Wedge Pressure; Regression Analysis; Ventricular Function

NT-pro-brain natriuretic peptide (NT-proBNP) values are correlated with right ventricle dysfunction in pulmonary hypertension and have been recommended as a prognostic marker for symptomatic primary pulmonary hypertension. The purpose of this pilot study was to determine whether NT-proBNP values correlate with mild to moderate pulmonary hypertension in Gaucher disease. The NT-proBNP assay was performed on sera from patients with type I (non-neuronopathic) Gaucher disease who were known to have tricuspid insufficiency (TI) gradient values on echocardiography that were normal (TI<20 mmHg), borderline (TI=25-29 mmHg), or abnormal (TI>or= 30 mmHg) over time. There was a statistically significant correlation (p=0.05) between mean NT-proBNP values and TI gradient group: mean NT-proBNP for normal TI gradient (n=20 patients)=133.3 (range: 46-445)pg/ml; mean NT-proBNP for borderline TI gradient (n=17 patients)=288.7 (range: 81-1088)pg/ml; and mean NT-proBNP for elevated TI gradient (n=10 patients)=1034.2 (73-6703)pg/ml. Treatment status was not correlated with TI gradient or NT-proBNP values. Thus, in this pilot study of Gaucher disease that included patients with mild to moderate pulmonary hypertension, NT-proBNP was correlated with echocardiographic findings. Further studies will be required to ascertain if NT-proBNP can be used for diagnosis and monitoring of these patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Child; Child, Preschool; Cohort Studies; Echocardiography; Female; Gaucher Disease; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Pilot Projects; Prognosis; Sensitivity and Specificity; Severity of Illness Index; Tricuspid Valve Insufficiency

Pulmonary hypertension especially arterial and idiopathic is still a poorly understood disease often affecting young adults and leading to right ventricular overload, failure and death due to low cardiac output. Justification for new, aggressive, costly but effective methods of pharmacological and interventional treatment of pulmonary hypertension require precise, repeatedly performed prognostic assessment. This is currently provided not only by repeated right heart catheterization but mostly by exercise testing as well as non-invasive techniques such as echo-Doppler and biochemical myocyte markers including B-type natriuretic peptide and cardiac troponin. Such methods should allow better timing of atrial septostomy and listing for lung transplantation.

Topics: Biomarkers; Cardiac Catheterization; Echocardiography, Doppler; Exercise Test; Humans; Hypertension, Pulmonary; Myocytes, Cardiac; Natriuretic Peptide, Brain; Prognosis; Troponin; Ventricular Dysfunction, Right

The continuous IV administration of prostacyclin improves pulmonary hemodynamics and prognosis in patients with primary pulmonary hypertension. We investigated whether the administration of prostacyclin therapy to patients before they undergo pulmonary thromboendarterectomy ameliorates pulmonary hypertension in patients with the most severe form of chronic thromboembolic pulmonary hypertension (CTEPH).. Of the 33 patients with CTEPH who were candidates for pulmonary thromboendarterectomy, 12 patients with severe pulmonary hypertension (pulmonary vascular resistance, > 1,200 dyne. s. cm(-5)) received IV prostacyclin prior to undergoing pulmonary thromboendarterectomy. Right heart catheterization and plasma brain natriuretic peptide (BNP) measurements were repeated at baseline, immediately before surgery, and 1 month after surgery.. During a mean (+/- SEM) follow-up period of 46 +/- 12 days, the IV administration of prostacyclin resulted in a 28% decrease in pulmonary vascular resistance (1,510 +/- 53 to 1,088 +/- 58 dyne. s. cm(-5); p < 0.001) before surgery. Prostacyclin therapy markedly decreased plasma BNP level (547 +/- 112 to 188 +/- 30 pg/mL; p < 0.01), suggesting improvement in right heart failure. Pulmonary thromboendarterectomy caused a further reduction of pulmonary vascular resistance (302 +/- 47 dyne. s. cm(-5)) and plasma BNP levels (60 +/- 11 pg/mL) compared to each preoperative value (p < 0.05). Operative mortality rates were relatively low (8.3%) in patients with the most severe form of CTEPH.. The IV administration of prostacyclin caused beneficial hemodynamic effects in patients with severe CTEPH and may serve as pretreatment for patients undergoing pulmonary thromboendarterectomy.

Topics: Adult; Aged; Antihypertensive Agents; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Endarterectomy; Epoprostenol; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Premedication; Prognosis; Pulmonary Embolism; Survival Rate; Vascular Resistance

Topics: Adult; Cardiotonic Agents; Dobutamine; Female; Humans; Hypertension, Pulmonary; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Natriuretic Peptide, Brain; Pulmonary Valve Insufficiency; Pulmonary Valve Stenosis; Stroke Volume; Tetralogy of Fallot; Ventricular Function, Right; Ventricular Pressure

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Aged; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Piperazines; Pulmonary Fibrosis; Purines; Raynaud Disease; Scleroderma, Systemic; Sildenafil Citrate; Sulfones

Plasma brain natriuretic peptide (BNP), a cardiac hormone secreted mainly by the cardiac ventricles, has been shown to increase in proportion to the degree of cardiac overload. However, whether plasma BNP may serve as a marker for the efficacy of pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension remains unknown.. Plasma BNP level was measured in 34 patients with chronic thromboembolic pulmonary hypertension before and 1 month after pulmonary thromboendarterectomy. Right heart catheterization was also performed before and 1 month after the operation.. Preoperative plasma BNP level was significantly elevated in patients with chronic thromboembolic pulmonary hypertension compared with control patients (246 +/- 40 vs 13 +/- 2 pg/mL; p < 0.001; n = 34) and was positively correlated with total pulmonary resistance (r = 0.57; p < 0.001). After pulmonary thromboendarterectomy, plasma BNP level in survivors markedly decreased (220 +/- 31 to 54 +/- 9 pg/mL; p < 0.001; n = 32) in association with a reduction of total pulmonary resistance (15.6 +/- 1.0 to 4.5 +/- 0.3 Wood units; p < 0.001). The change in plasma BNP level was closely correlated with that in total pulmonary resistance (r = 0.63; p < 0.001). Importantly, a sustained elevation of plasma BNP (> or = 50 pg/mL) indicated the presence of residual pulmonary hypertension (> or = 5 Wood units) after operation (sensitivity = 73%; specificity = 81%).. Plasma BNP level was strongly associated with the severity of pulmonary hypertension in patients with chronic thromboembolic pulmonary hypertension and thereby may serve as a noninvasive marker for the efficacy of pulmonary thromboendarterectomy.

Topics: Adult; Biomarkers; Endarterectomy; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Period; Pulmonary Embolism; Treatment Outcome

Plasma brain natriuretic peptide (BNP) level increases in proportion to the degree of right ventricular dysfunction in pulmonary hypertension. We sought to assess the prognostic significance of plasma BNP in patients with primary pulmonary hypertension.. Plasma BNP was measured in 60 patients with primary pulmonary hypertension at diagnostic catheterization, together with atrial natriuretic peptide, norepinephrine, and epinephrine. Measurements were repeated in 53 patients after a mean follow-up period of 3 months. Forty-nine of the patients received intravenous or oral prostacyclin. During a mean follow-up period of 24 months, 18 patients died of cardiopulmonary causes. According to multivariate analysis, baseline plasma BNP was an independent predictor of mortality. Patients with a supramedian level of baseline BNP (> or = 150 pg/ml) had a significantly lower survival rate than those with an inframedian level, according to Kaplan-Meier survival curves (p < 0.05). Plasma BNP in survivors decreased significantly during the follow-up (217 +/- 38 to 149 +/- 30 pg/ml, p < 0.05), whereas that in nonsurvivors increased (365 +/- 77 to 544 +/- 68 pg/ml, p < 0.05). Thus, survival was strikingly worse for patients with a supramedian value of follow-up BNP (> or = 180 pg/ml) than for those with an inframedian value (p < 0.0001).. A high level of plasma BNP, and in particular, a further increase in plasma BNP during follow-up, may have a strong, independent association with increased mortality in patients with primary pulmonary hypertension.

Topics: Biomarkers; Follow-Up Studies; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Prognosis

This study investigated whether plasma levels of adrenomedullin, a potent vasodilating endogenous neurohumoral mediator, are useful for assessing the severity of primary pulmonary hypertension.. Seventeen pediatric patients with primary pulmonary hypertension (eight girls, nine boys, mean age 12 +/- 4 years) were enrolled in this study. Thirteen patients in New York Heart Association (NYHA) classes III and IV had been treated with long-term continuous intravenous prostacyclin (PGI2) infusion therapy, and four patients in classes I and II had received beraprost sodium, an oral PGI2 analogue. Blood samples were taken from all patients at the first visit. Plasma levels of atrial and brain natriuretic peptide (ANP, BNP) and endothelin-1, and mature-type adrenomedullin were measured. The relationships were investigated between neurohumoral mediator levels and NYHA class, pulmonary hemodynamics, and exercise capacity assessed by 6-minute walk test. The changes in neurohumoral mediator levels at 1 month, 3 months, and 6 to 12 months were also evaluated in 11 survivors with long-term PGI2 treatment.. All neurohumoral mediator levels were positively correlated with severity of NYHA class. Patients in class IV demonstrated significantly elevated neurohumoral mediator levels, except endothelin-1, in comparison with patients in classes I-III. Neurohumoral mediator levels had a significant negative correlation with exercise capacity. Stepwise regression analysis revealed that the BNP to ANP ratio (BNP/ANP) was the most powerful independent factor for total pulmonary resistance (r = 0.85, p = 0.0071) and cardiac index (r = 0.84, p = 0.009). Adrenomedullin was significantly correlated with BNP (r = 0.53, p = 0.03), endothelin-1 (r = 0.66, p = 0.006), and BNP/ANP (r = 0.73, p = 0.0009). ANP and BNP decreased from 196 +/- 213 and 494 +/- 361 pg/ml at baseline to 74 +/- 47 and 153 +/- 133 pg/ml at 1 month, respectively. There was an apparent re-increase in both ANP (187 +/- 194 pg/ml) and BNP (466 +/- 621 pg/ml) at 3 months, regardless of improvement in NYHA class and exercise capacity after long-term PGI2 treatment. In contrast, adrenomedullin decreased from 3.0 +/- 2.2 (baseline) to 1.7 +/- 0.7 fmol/ml at 1 month and 1.6 +/- 0.5 fmol/ml at 3 months. Adrenomedullin was slightly increased at 6-12 months (2.1 +/- 0.9 fmol/ml) without statistical significance. There was a significant relationship between the changes in adrenomedullin at 3 months compared to values at initiation of PGI2 therapy and the changes in mean pulmonary arterial pressure (r = 0.97, p = 0.0041).. Plasma levels of neurohumoral mediators are useful for assessing the severity of primary pulmonary hypertension. In particular, adrenomedullin was valuable for evaluating both cardiac performance and pulmonary hemodynamics after long-term treatment with PGI2 in patients with primary pulmonary hypertension.

Topics: Adolescent; Adrenomedullin; Antihypertensive Agents; Atrial Natriuretic Factor; Child; Child, Preschool; Endothelin-1; Epoprostenol; Exercise Tolerance; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Male; Natriuretic Peptide, Brain; Peptides

Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) both have diuretic, natriuretic, and hypotensive effects, and both are involved in cardiovascular homeostasis as cardiac hormones. To study the effects of HHE on the natriuretic peptide synthesis system, 170 male Wistar rats were housed in a chamber at the equivalent of the 5500-m altitude level for 1-12 weeks. After 1 week of HHE, pulmonary arterial pressure was significantly raised, and the ratio of left ventricle plus septum over right ventricle of the heart showed a significant decrease (compared with those of ground-level control rats). In both ventricular tissues, the expression of ANP messenger (m)RNA and BNP mRNA increased after exposure to HHE. The amounts of ANP and BNP had decreased significantly in right atrial tissue at 12 weeks of HHE (compared with those of the controls), whereas in ventricular tissues at the same time point, both levels had increased significantly. In in situ hybridization and immunohistochemical studies, the staining of the mRNAs for ANP and BNP and of ANP and BNP themselves was more intense in both ventricular tissues after exposure to HHE than before (i.e., in the controls). The results suggest that, in response to HHE, the changes in ventricular synthesis are similar for ANP and BNP. These changes may play a role in modulating pulmonary hypertension in HHE. However, under our conditions, pulmonary hypertension increased progressively throughout the HHE period.

Topics: Altitude Sickness; Animals; Atmosphere Exposure Chambers; Atmospheric Pressure; Atrial Natriuretic Factor; Blotting, Northern; Disease Models, Animal; Fluorescent Antibody Technique, Indirect; Heart Ventricles; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Immunoenzyme Techniques; In Situ Hybridization; Male; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Wistar; RNA, Messenger; Time Factors

Continuous intravenous infusion of prostacyclin (epoprostenol) as a treatment for primary pulmonary hypertension (PPH) definitely improves the patient's quality of life, but few accurate parameters have been found to evaluate the efficacy of the treatment. We observed a patient with severe PPH whose plasma brain natriuretic peptide (BNP) level changed significantly as her condition and symptoms changed. Plasma BNP may be considered as one of the parameters for assessing the efficacy of prostacyclin treatment.

Topics: Adolescent; Antihypertensive Agents; Biomarkers; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Infusions, Intravenous; Natriuretic Peptide, Brain; Prognosis; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome

Endothelin (ET)-1 has potent positive inotropic and chronotropic activity in the heart and induces cardiac hypertrophy. The production of ET-1 in the heart is reported to be increased under some conditions. In normal circulation, the pressure load to the left ventricle (LV) is much greater than that to the right ventricle (RV). In this study, we investigated the gene expression of the myocardial ET-1 system (ET-1, ET(A) receptor, and ET(B) receptor) in the RV and LV of normal rats and also investigated these genes in hypertrophied RV due to pathological pulmonary hypertension (PH). Normal rats showed no differences between the RV and LV in the gene expression of either ET-1, ET(A) receptor, or ET(B) receptor in either the adult stage (11 wk old) or the neonatal stage (1 and 8 days old). On the other hand, the expression of both atrial natriuretic peptide (ANP) mRNA and B-type natriuretic peptide (BNP) mRNA was significantly greater in the LV than in the RV in adult rats. Gene expression of ET-1, ET(A) receptor, and ET(B) receptor in the RV was markedly higher in rats with monocrotaline-induced (pathological) PH than that in control rats. The expression of ANP mRNA and BNP mRNA in the RV was also markedly higher in the rats with PH. In conclusion, the data suggest that gene expression of the ET-1 system in the myocardium is not affected by physiological pressure load in either the adult stage or neonatal stage; however, it is enhanced by pathological pressure overload such as that in PH.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; DNA, Complementary; Endothelin-1; Endothelins; Gene Expression; Hypertension, Pulmonary; Male; Monocrotaline; Myocardium; Natriuretic Peptide, Brain; Protein Precursors; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Receptor, Endothelin B; Receptors, Endothelin; RNA, Messenger; Ventricular Function, Left; Ventricular Function, Right

This study sought to investigate the influence of right ventricular (RV) hemodynamic variables and function on the secretion of brain natriuretic peptide (BNP) in patients with isolated RV overload.. Plasma BNP is known to increase in proportion to the degree of left ventricular (LV) overload. However, whether BNP secretion is also regulated in the presence of RV overload remains unknown.. Plasma BNP and atrial natriuretic peptide (ANP) levels in the pulmonary artery were measured in 44 patients with RV overload: 18 with RV volume overload (RVVO) due to atrial septal defect and 26 with RV pressure overload (RVPO) due to primary or thromboembolic pulmonary hypertension. Right heart catheterization was performed in all patients. RV and LV ejection fraction, myocardial mass and volume of the four chambers were determined by using electron beam computed tomography.. Although both plasma BNP and ANP levels were significantly elevated in patients with RV overload compared with values in control subjects, plasma BNP and the BNP/ANP ratio were significantly higher in patients with RVPO than with RVVO (BNP 294 +/- 72 vs. 48 +/- 14 pg/ml; BNP/ANP 1.6 +/- 0.2 vs. 0.8 +/- 0.2, both p < 0.05). Plasma BNP correlated positively with mean pulmonary artery pressure (r = 0.73), total pulmonary resistance (r = 0.79), mean right atrial pressure (r = 0.79), RV end-diastolic pressure (r = 0.76) and RV myocardial mass (r = 0.71); it correlated negatively with cardiac output (r = -0.33) and RV ejection fraction (r = -0.71). Plasma BNP significantly decreased from 315 +/- 120 to 144 +/- 54 pg/ml with long-term vasodilator therapy (total pulmonary resistance decreased from 23 +/- 4 to 15 +/- 3 Wood U).. Plasma BNP increases in proportion to the extent of RV dysfunction in pulmonary hypertension.

Topics: Adult; Aged; Atrial Natriuretic Factor; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Tomography, X-Ray Computed; Ventricular Dysfunction, Right

Brain natriuretic peptide (BNP) is a pulmonary vasodilator that is elevated in the right heart and plasma of hypoxia-adapted rats. To test the hypothesis that BNP protects against hypoxic pulmonary hypertension, we measured right ventricular systolic pressure (RVSP), right ventricle (RV) weight-to-body weight (BW) ratio (RV/BW), and percent muscularization of peripheral pulmonary vessels (%MPPV) in rats given an intravenous infusion of BNP, atrial natriuretic peptide (ANP), or saline alone after 2 wk of normoxia or hypobaric hypoxia (0.5 atm). Hypoxia-adapted rats had higher hematocrits, RVSP, RV/BW, and %MPPV than did normoxic controls. Under normoxic conditions, BNP infusion (0.2 and 1.4 micro g/h) increased plasma BNP but had no effect on RVSP, RV/BW, or %MPPV. Under hypoxic conditions, low-rate BNP infusion (0.2 micro g/h) had no effect on plasma BNP or on severity of pulmonary hypertension. However, high-rate BNP infusion (1.4 micro g/h) increased plasma BNP (69 +/- 8 vs. 35 +/- 4 pg/ml, P < 0.05), lowered RV/BW (0.87 +/- 0.05 vs. 1.02 +/- 0.04, P < 0.05), and decreased %MPPV (60 vs. 74%, P < 0.05). There was also a trend toward lower RVSP (55 +/- 3 vs. 64 +/- 2, P = not significant). Infusion of ANP at 1.4 micro g/h increased plasma ANP in hypoxic rats (759 +/- 153 vs. 393 +/- 54 pg/ml, P < 0.05) but had no effect on RVSP, RV/BW, or %MPPV. We conclude that BNP may regulate pulmonary vascular responses to hypoxia and, at the doses used in this study, is more effective than ANP at blunting pulmonary hypertension during the first 2 wk of hypoxia.

Topics: Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Heart Ventricles; Hemodynamics; Histocytochemistry; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Lung; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Sprague-Dawley; Vasodilator Agents

BACKGROUND This study was designed to investigate plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with atrial septal defect (ASD), whose right ventricular loading patterns vary from simple volume overloading to both volume and pressure overloading.. Plasma ANP and BNP in the pulmonary artery were measured in 31 adult patients with ASD and 11 control subjects. On the basis of the presence of pulmonary hypertension (PH, mean pulmonary arterial pressure >20 mm Hg), patients with ASD were divided into two groups, patients without PH (group 1, n = 21) and those with PH (group 2, n = 10). Cardiac catheterization was performed to measure mean pulmonary arterial pressure and pulmonary blood flow. Plasma ANP was significantly higher in both group 1 and group 2 than in the control group. Plasma BNP and BNP to ANP (BNP/ANP) ratio were significantly higher in group 2 than in the control group, although they were not significantly elevated in group 1. Plasma ANP positively correlated with the degree of pulmonary blood flow (r = 0.54, p < 0.01), whereas plasma BNP positively correlated with the magnitude of mean pulmonary arterial pressure (r= 0.73, p < 0.001). BNP/ANP >1 was a powerful marker for the presence of PH (sensitivity 90%, specificity 90%).. Plasma ANP levels were elevated in adult patients with ASD regardless of PH. In contrast, plasma BNP levels were elevated in proportion to the severity of PH complicating ASD. Thus BNP and ANP may represent differing aspects of cardiac response to right ventricular overload in patients with ASD.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiac Catheterization; Female; Heart Septal Defects, Atrial; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Pulmonary Wedge Pressure; Reference Values; Ventricular Function, Right

To examine the pathophysiological significance of adrenomedullin in the pulmonary circulation by investigating the relation between plasma concentrations of adrenomedullin and central haemodynamics in patients with mitral stenosis.. Plasma concentrations of adrenomedullin in blood samples obtained from the femoral vein, pulmonary artery, left atrium, and aorta were measured by a newly developed specific radio-immunoassay in 23 consecutive patients with mitral stenosis (16 females and seven males, aged 53 (10) years (mean (SD)) who were undergoing percutaneous mitral commissurotomy.. Patients with mitral stenosis had higher concentrations of adrenomedullin than age matched normal controls (3.9 (0.3) v 2.5 (0.3) pmol/l, p < 0.001). There was a reduction in adrenomedullin concentrations between the pulmonary artery and the left atrium (3.8 (0.2) v 3.2 (0.4) pmol/l, p < 0.001). The venous concentrations of adrenomedullin correlated with mean pulmonary artery pressure (r = 0.65, p < 0.001), total pulmonary vascular resistance (r = 0.83, p < 0.0001), and pulmonary vascular resistance (r = 0.65, p < 0.001). Plasma concentrations of adrenomedullin did not change immediately after percutaneous mitral commissurotomy; however, they decreased significantly one week later.. Plasma concentrations of adrenomedullin are increased in patients with mitral stenosis. This may help to attenuate the increased pulmonary arterial resistance in secondary pulmonary hypertension due to mitral stenosis.

Topics: Adrenomedullin; Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mitral Valve Stenosis; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptides; Pulmonary Circulation; Vascular Resistance

Topics: Atrial Natriuretic Factor; Humans; Hypertension, Pulmonary; Hypocapnia; Hypoxia; Natriuretic Peptide, Brain; Nerve Tissue Proteins

Topics: Atrial Natriuretic Factor; Blood Pressure; Gene Expression Regulation; Guanylate Cyclase; Humans; Hypertension, Pulmonary; Hypoxia; Lung Diseases, Obstructive; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Proteins; Receptors, Atrial Natriuretic Factor; Up-Regulation; Vascular Resistance; Vasodilator Agents

Topics: Female; Humans; Hypertension, Pulmonary; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Nifedipine; Vascular Resistance

To test the hypothesis that brain natriuretic peptide (BNP) plays a role similar to that of atrial natriuretic peptide (ANP) in modulating pulmonary vascular responses to hypoxia, we measured the vasodilator potency of ANP and BNP in rat pulmonary artery (PA) and thoracic aorta (TA) rings and in isolated rat lungs. We also measured the effect of chronic hypoxia on plasma levels and cardiac gene expression of both peptides. BNP had a vasorelaxant effect equipotent to that of ANP on preconstricted TA and PA rings, but was less potent than ANP in relaxing the vasoconstrictor response to hypoxia in isolated lungs [mean 50% inhibitory concentration (IC50) 10(-7) vs. 10(-6) M for ANP and BNP, respectively]. Plasma BNP levels were 30-fold lower than ANP, but both peptides increased approximately 70% during chronic hypoxia. In the right atrium, hypoxia lowered BNP mRNA slightly, but had no effect on ANP mRNA or tissue levels of either peptide. However, hypoxia increased right ventricular content and mRNA levels of both peptides by three- to fourfold. We conclude that BNP and ANP have similar pulmonary vasodilator effects and are upregulated proportionally during chronic hypoxia. These results support a role for BNP in modulating the pulmonary hypertensive response to chronic hypoxia.

Topics: Animals; Aorta, Thoracic; Atrial Natriuretic Factor; Base Sequence; Hypertension, Pulmonary; Hypoxia; In Vitro Techniques; Lung; Male; Molecular Sequence Data; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Oligonucleotide Probes; Pulmonary Artery; Rats; Rats, Sprague-Dawley; RNA, Messenger