Biomarker N-terminal Pro-brain Natriuretic Peptide Research Articles

INVESTIGATION OF CENTRAL HEMODYNAMICS VIA RIGHT HEART AND PULMONARY ARTERY CATHETERIZATION IN PATIENTS WITH SYSTEMIC CONNECTIVE TISSUE DISEASES

Pulmonary arterial hypertension (PAH) associated with systemic connective tissue diseases (SCTD) is a poor prognostic manifestation of the latter that result in death if untreated. The invasive determination of hemodynamic parameters is prominent in diagnosing the disease and determining its treatment policy and prognosis. Objective : to analyze the results of catheterization in PAH-SCTD patients admitted to the V.A. Nasonova Research Institute of Rheumatology. Subjects and methods . The investigation included 59 patients admitted to the V.A. Nasonova Research Institute of Rheumatology from September 2009 to September 2014. PAH was diagnosed in accordance with the conventional guidelines. All the patients underwent right heart and pulmonary artery (PA) catheterization at the diagnosis and over time during treatment. Results and discussion. All the patients included in the trial met the pre-capillary pulmonary hypertension (PH) criteria: mean pulmonary artery pressure (MPAP) ≥25 mm Hg; and PA wedge pressure (PAWP) 15 mm Hg and pulmonary vascular resistance (PVR) >3 Wood units could diagnose PAH in all our patients. There was a statistically highly significant association between pathological hemodynamic changes and functional class (FC). FC was found to be most closely correlated with right atrial pressure (RAP), cardiac output (CO), PVR, and cardiac index (CI). Among the most common manifestations of heart failure, only the presence of peripheral edemas was associated with worse hemodynamic parameters in PAH. It should be noted that out of two biomarkers (N-terminal pro-brain natriuretic peptide and uric acid), the former is largely related to the magnitude of changes in hemodynamic factors. The critical values of hemodynamic parameters were due to extreme edema – anasarca (RAP >17 mm Hg, PVR >20 Wood units, CI <14 ml/m2). Analysis of clinical and instrumental parameters in relation to FC revealed a linear relationship of RAP, CO, and PVR between the level of these parameters and FC; moreover, the highest correlation coefficients were observed for the hemodynamic parameters characterizing right ventricular systolic function. It is remarkable that no MPAP changes were found; only patients with FC IV showed its slight increase (from 51±8 to 55±8 mm Hg; р = 0.087). PAWP remained unchanged regardless of FC. Conclusion. Thus, the hemodynamic parameters determined in patients with PAH-SCTD during right heart and LA catheterization are closely related to the manifestations of respiratory and heart failure, the biomarkers, and FC of PAH.

Impact of Immunosuppressive Treatment on the Cardiovascular System in Patients After Hand Transplantation

BackgroundCardiovascular disease is a major cause of mortality in solid organ allograft recipients. Hand transplantation is not a lifesaving procedure, thus the effect of long-term immunosuppression on the cardiovascular system in these patients should be monitored. The aim of this study was to evaluate the morphology and function of heart and blood vessels in patients after hand transplantation. MethodsThe study included 5 patients at ages 32 to 58 years, mean 39 years, who underwent hand transplantation between 2006 and 2010. Immunosuppressive treatment included basiliximab in induction and tacrolimus, mycophenolate mofetil, and prednisone. Cardiac status was assessed by echocardiography (according to the American Society of Echocardiography) and cardiac biomarkers. Blood vessels were estimated by carotid intima-media thickness, pulse wave velocity, and brachial artery flow-mediated dilatation (FMD). The examinations were performed at 28 to 79 (mean 43) months after transplantation. ResultsCardiovascular risk factors were observed in all patients after transplantation: 2 had insulin-dependent diabetes, 3 developed dyslipidemia and hypertension, 2 had chronic kidney disease stage 3. Concentric left ventricular hypertrophy was found in 1 and ventricular concentric remodeling in 4 patients. Impaired diastolic function (E/e’ > 8) was observed in 2 patients. The index volume of the left atrium was higher in all patients. The cardiac biomarkers N-terminal pro-brain natriuretic peptide, C-reactive protein, and troponins were within normal range. Carotid intima-media thickness was higher in 1 patient and normal in 4 patients. Arterial stiffness measured by pulse wave velocity was not increased in all patients. Native brachial artery FMD response, an index of endothelium-dependent function, was abnormal in 2 patients, but in the transplanted extremity FMD was abnormal in 4 patients. ConclusionsPathologic changes in cardiac structures were found in all patients, but the arterial wall changes and endothelial dysfunction were observed in some patients. Patients after hand transplantation are at higher risk for cardiovascular disease.

Balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension

ObjectiveTo 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.DesignObservational cohort study.SettingReferred patients...

Nanosensor Electrical Immunoassay for Quantitative Detection of NT-pro Brain Natriuretic Peptide

To demonstrate a label-free electrical immunoassay for profiling vascular biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) associated with improved cardiac risk prediction. A high-density nanowell-based electrical immunoassay has been designed by integrating nanoporous aluminum oxide onto printed circuit board chips for the detection of NT-proBNP. The concentration of the biomarker is quantitatively determined by measuring impedance changes to the electrical double layer within the nanowells using electrochemical impedance spectroscopy. Detection sensitivity in the fg/ml range was obtained due to spatial confinement of the target biomarkers in size-matched nanowells. Electrical immunoassay performance was determined for the detection of NT-proBNP in phosphate-buffered saline (PBS) and human serum (HS). The lower limit of detection for the sensor was observed to be 10 fg/ml in PBS and 500 fg/ml in HS. The upper limit of detection was observed to be 500 fg/ml in PBS and 500 ng/ml in HS. A label-free technique for detection of NT-proBNP at clinically relevant concentrations for evaluating cardiac risk is demonstrated. High sensitivity and specificity, robust detection and low volume (100 µl) per assay project the technology to be a successful competitor to traditional ELISA-based techniques.

Performance Trends and Cardiac Biomarkers in a 30-km Cross-Country Race, 1993–2007

Long-distance running events enjoy increasing popularity in all ages. Whereas the health benefits of regular moderate exercise are undisputed, the net health effects of single or repeated participation in endurance events of marathon type remain to be determined. We wanted to investigate performance trends over time and the relationship between race performance and cardiac biomarker levels among participants in a large annual 30-km cross-country race. We analyzed a database containing age, gender, run times, and previous race participation of 124,608 runners finishing the Lidingöloppet (30 km) between 1993 and 2007. In 249 male runners age ≥ 45 yr, we also performed a thorough cardiovascular examination, including measuring the cardiac biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin. Total participation increased 56% with the largest gains in younger female and older male runners. Mean run times rose from 164 ± 27 min in 1993 to 184 ± 33 min in 2007 (P < 0.001) in men and from 179 ± 26 to 203 ± 32 in women (P < 0.001) after a strong linear relationship (men, r = 0.98; women, r = 0.93). Increased run times were seen in the mean, top, and bottom quartiles as well as in the top and bottom 5% of all age and gender groups. In the substudy among 249 older male runners, not only higher body mass index, older age, and fewer previous race participations but also higher baseline NT-proBNP was independently associated with increased run time. Whereas participation in the Lidingöloppet increased, fitness deteriorated over time in both genders and in all ages. In a subset of older male athletes, longer run times were associated with higher levels of NT-proBNP. The present findings may support the usefulness of preparticipation evaluation to ensure appropriate fitness and cardiovascular health in long-distance race participants.

N-Terminal Pro-Brain Natriuretic Peptide and Angiotensin-Converting Enzyme-2 Levels and Their Association With Postoperative Cardiac Complications After Emergency Orthopedic Surgery

The prognostic usefulness of the cardiac biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and angiotensin-converting enzyme 2 (ACE-2), in predicting adverse cardiac outcomes after orthopedic surgery is not well studied. The aim of our study was to determine the usefulness of perioperative NT-proBNP and ACE-2 for predicting cardiac events after emergency orthopedic surgery. The perioperative NT-proBNP and ACE-2 levels were determined in 187 consecutive patients aged >60 years who underwent orthopedic surgery with 1 year of follow-up for any cardiac complications (defined as acute myocardial infarction, congestive cardiac failure, atrial fibrillation, or major arrhythmia) and death. Of the 187 patients, 20 (10.7%) sustained an in-hospital postoperative cardiac complication. The total all-cause in-hospital and 1-year mortality rate was 1.6% (3 of 187) and 8.6% (16 of 187), respectively. The median preoperative and postoperative NT-proBNP level was greater in patients who sustained an in-hospital cardiac event than in those who had not (386 vs 2,273 pg/ml, p <0.001, and 605 vs 4,316 pg/ml, p <0.001, respectively). Similarly, the postoperative median ACE-2 levels were significantly greater in the patients with an in-hospital cardiac event than in those without (25.3 vs 39.5 pmol/ml/min, p = 0.012). A preoperative NT-proBNP level of ≥741 pg/ml (odds ratio 4.5, 95% confidence interval 1.3 to 15.2, p = 0.017), postoperative troponin elevation (odds ratio 4.9, 95% confidence interval 1.3 to 18.9, p = 0.022), and number of co-morbidities (odds ratio 1.8, 95% confidence interval 1.2 to 2.8, p = 0.009) independently predicted in-hospital cardiac complications on multivariate analysis. The pre- and postoperative NT-proBNP level independently predicted 1-year cardiovascular complications but not the ACE-2 levels. In conclusion, elevated perioperative NT-proBNP predicted in-hospital and 1-year cardiac events in an emergency orthopedic population but the ACE-2 levels did not, which requires additional study for validation.

Signal-enhancer molecules encapsulated liposome as a valuable sensing and amplification platform combining the aptasensor for ultrasensitive ECL immunoassay

An innovatory ECL immunoassay strategy was proposed to detect the newly developing heart failure biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP). Firstly, this strategy used small molecules encapsulated liposome as immune label to construct a sandwich immune sensing platform for NT-proBNP. Then the ECL aptasensor was prepared to collect and detect the small molecules released from the liposome. Finally, based on the ECL signal changes caused by the small molecules, the ECL signal indirectly reflected the level of NT-proBNP antigen. In this experiment, the cocaine was chosen as the proper small molecule that can act as signal-enhancer to enhance the ECL of Ru(bpy) 3 2+. The cocaine-encapsulated liposomes were successfully characterized by TEM. The quantificational calculation proved the ∼5.3 × 10 3 cocaine molecules per liposome enough to perform the assignment of signal amplification. The cocaine-binding ECL aptasensor further promoted the work aimed at amplifying signal. The performance of NT-proBNP assay by the proposed strategy exhibited high sensitivity and high specificities with a linear relationship over 0.01–500 ng mL −1 range, and a detection limit down to 0.77 pg mL −1.

Effect of heart rate reduction by ivabradine on left ventricular remodeling in the echocardiographic substudy of BEAUTIFUL

Occlusive coronary artery disease (CAD) is associated with left ventricular (LV) remodeling, LV systolic dysfunction, and heart failure. The BEAUTIFUL Echo substudy aimed to evaluate the effects of heart rate reduction with ivabradine on LV size (primary end-point: change in LV end-systolic volume index [LVESVI]) and function and the cardiac biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP). The substudy was carried out in 86 centers participating in the BEAUTIFUL study. 2D echocardiography was performed at baseline, and after 3 and 12 months in patients with stable CAD and LV systolic dysfunction receiving ivabradine or placebo at the same time-points. All data were read and analyzed centrally. Of 525 patients completing the study, 426 had adequate echocardiographic readings (n = 220 ivabradine; n = 206 placebo). Treatment with ivabradine was associated with a decrease in the primary end-point LVESVI (change from baseline to last value, -1.48 ± 13.00 mL/m(2)) versus an increase with placebo (1.85 ± 10.54 mL/m(2)) (P=0.018). There was an increase in LV ejection fraction with ivabradine (2.00 ± 7.02%) versus no change with placebo (0.01 ± 6.20%) (P=0.009). Reduction in LVESVI was related to the degree of heart rate reduction with ivabradine. There were no differences in any other echocardiographic parameters or NT-proBNP. Change in LVESVI was related to the log change in NT-proBNP in the ivabradine group only (r = 0.18, P = 0.006). Our observations suggest that ivabradine may reverse detrimental LV remodeling in patients with CAD and LV systolic dysfunction.

Subclinical coronary artery disease in Asian rheumatoid arthritis patients who were in remission: a pilot study

Rheumatoid arthritis (RA) patients who have active disease with longer disease duration have been reported to have increased risk of cardiovascular events compared to the normal population. The primary aim of our study is to ascertain the prevalence of significant asymptomatic coronary artery disease (CAD) in Asian RA patients who are in remission using multi-detector computed tomography (MDCT). The secondary aims of our study are the usage of pulse wave velocity and the biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-senstivity C-reactive protein (hs-CRP) to detect subclinical atherosclerosis in RA patients. We performed a comparative cross-sectional study of 47 RA patients who were in remission with a control group of non-RA patients with a history of atypical chest pain in Sarawak General Hospital from November 2008 to February 2009. All patients underwent 64-slice MDCT, assessment of arterial stiffness using the SphygmoCor test and blood analysis for NT-proBNP and hsCRP. There were 94 patients in our study with a mean age of 50 +/- 8.8 years. The RA and control patients in each group were matched in terms of traditional CV risk factors. Our RA patients had a median disease duration of 3 years (IQR 5.5). MDCT showed evidence of CAD in nine (19.1%) RA patients and three (6.4%) control patients (P = 0.06). There was no significant association between pulse wave velocity (PWV) and presence of CAD in our RA group. There was no significant correlation between PWV with levels of proBNP or hsCRP in our RA patients. In our current pilot study with the limitation of small sample size, RA was not associated with an increased risk of CAD in our RA patients who were in remission. Larger studies of CAD in Asian RA patients are needed to confirm our current finding.

Addition of Inhaled Treprostinil to Oral Therapy for Pulmonary Arterial Hypertension: A Randomized Controlled Clinical Trial

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).

N-Terminal Pro-Brain Natriuretic Peptide as a Biomarker for Hypertensive Disorders of Pregnancy

We tested the hypothesis that the cardiac biomarker N-terminal pro-brain natriuretic peptide would be elevated in hypertensive disorders of pregnancy, with an increase in levels of this biomarker across increasing gradations of disease severity. We performed a case-controlled study of women admitted to labor and delivery at the Hospital of the University of Pennsylvania between 24 and 42 weeks of gestation. Cases had hypertension that developed after 20 weeks of gestation, and controls were normotensive women presenting for delivery. N-terminal pro-brain natriuretic peptide levels were compared between cases ( N = 83) and controls ( N = 290). Cases were subclassified into gestational hypertension ( N = 20) and mild ( N = 15) and severe preeclampsia ( N = 48), and N-terminal pro-brain natriuretic peptide levels were compared between these subgroups. N-terminal pro-brain natriuretic peptide levels were higher in cases than in controls (81 pg/mL versus 37 pg/mL, P < 0.001), with a graded increase in levels from gestational hypertension (64 pg/mL) to preeclampsia (89 pg/mL) to severe preeclampsia (157 pg/mL; P < 0.001). Each log increase in N-terminal pro-brain natriuretic peptide doubled the risk of preeclampsia (odds ratio = 2.10 P < 0.001). N-terminal pro-brain natriuretic peptide levels were increased in hypertensive disorders of pregnancy and discriminate between subcategories of disease.