scholarly journals Total NT-proBNP, a novel biomarker related to recurrent atrial fibrillation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lidia Staszewsky ◽  
Jennifer M. T. A. Meessen ◽  
Deborah Novelli ◽  
Ursula-Henrike Wienhues-Thelen ◽  
Marcello Disertori ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Regression Analysis ◽  
Growth Factor ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Binding Protein ◽  
Circulating Biomarkers ◽  
Total N ◽  
Fatty Acid Binding ◽  
Recurrent Atrial Fibrillation

Abstract Background Novel circulating biomarkers may help in understanding the underlying mechanisms of atrial fibrillation (AF), a challenge for AF management and prevention of cardiovascular (CV) events. Whether glycosylation affects the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in AF is still unknown. Objectives To test how deglycosylated total NT-proBNP, NT-proBNP and a panel of biomarkers are associated with: (1) recurrent AF, (2) first hospitalization for CV reasons. Methods A total of 382 patients of the GISSI-AF trial in sinus rhythm with a history of AF, echocardiographic variables, total NT-proBNP, NT-proBNP and nine additional biomarkers [Total N-terminal pro-B type natriuretic peptide (Total NT proBNP), N-terminal pro-B type natriuretic peptide (NTproBNP), Angiopoietin 2 (Ang2), Bone morphogenic protein-10 (BMP10), Dickkopf-related protein-3 (DKK3), Endothelial cell specific molecule-1 (ESM1), Fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor-15 (GDF15), Insulin-like growth factor-binding protein-7 (IGFBP7) and Myosin binding protein C3 (MYPBC3)]. were assayed at baseline, 6 and 12 months under blind conditions in a laboratory at Roche Diagnostics, Penzberg, Germany. The associations between circulating biomarkers and AF at the 6- and 12-month visits, and their predictive value, were assessed in multivariable models with logistic regression analysis and Cox proportional hazards regression analysis. Biomarkers associations were modelled for 1SD increase in their level. Results Over a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for CV reasons. Total NT-proBNP, NT-proBNP, Ang2 and BMP10 showed the strongest associations with ongoing AF. Natriuretic peptides also predicted recurrent AF (total NT-proBNP: HR:1.19[1.04–1.36], p = 0.026; NT-proBNP: HR:1.19[1.06–1.35], p = 0.016; Ang2: HR:1.07[0.95–1.20], p = 0.283; BMP10: HR:1.09[0.96–1.25], p = 0.249) and CV hospitalization (total NT-proBNP: HR:1.57[1.29–1.90], p < 0.001 1.63], p = 0.097). Conclusions The association of total NT-proBNP with the risk of AF first recurrence was similar to that of NT-proBNP, suggesting no influence of glycosylation. Analogous results were obtained for the risk of first hospitalization for CV reasons. Natriuretic peptides, Ang2 and BMP10 were associated with ongoing AF. Findings from the last two biomarkers point to a pathogenic role of cardiac extracellular matrix and cardiomyocyte growth in the myocardium of the right atrium and ventricle.

Heart-type fatty acid binding protein in elective cardioversion of atrial fibrillation

2011 ◽  
Vol 44 (12) ◽  
pp. 947-949 ◽  
Author(s):  
Eftihia Sbarouni ◽  
Panagiota Georgiadou ◽  
Antigoni Chaidaroglou ◽  
Dimitris Degiannis ◽  
Vassilis Voudris
Keyword(s):  
Atrial Fibrillation ◽  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

Prediction of atrial fibrillation by 12-lead electrocardiogram parameters in patients without structural heart disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Hirota ◽  
S Suzuki ◽  
T Arita ◽  
N Yagi ◽  
T Otsuka ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Regression Analysis ◽  
Heart Diseases ◽  
P Wave ◽  
Funding Source ◽  
Predictive Capability ◽  
Predicting Model ◽  
Total N ◽  
Cox Regression Analysis ◽  
Relative Contribution

Abstract Background Recently, the analysis of electrocardiogram (ECG) waveform by artificial intelligence has been reported to pick out those who have atrial fibrillation (AF) or have a high potential of developing AF, which, however, cannot explain the mechanisms or algorisms for the prediction from its nature. Purpose The purpose of this study is to conduct a comprehensive analysis to investigate the difference of weighting in predicting capability for AF among hundreds of automatically-measured ECG parameters using a single ECG at sinus rhythm. Methods and results Out of Shinken Database 2010–2017 (n=19170), 12825 patients were extracted, where those with ECG showing AF rhythm at the initial visit (including all persistent/permanent AF and a part of paroxysmal AF) and those with structural heart diseases were excluded. Out of 639 automatically-measured ECG parameters in MUSE data management system (GE Healthcare, USA), 438 were used. [Analysis 1] A predicting model for paroxysmal AF were determined by logistic regression analysis (Total, n=12825; paroxysmal AF, n=1138), showing a high predictive capability (AUC = 0.780, p&lt;0.001). In this model, the relative contribution of ECG parameters (by coefficient of determination) according to the time phase were P:72.4%, QRS:32.7%, and ST-T:13.7%, respectively (Figure A). [Analysis 2] Excluding AF at baseline, a predicting model for new-developed AF were determined by Cox regression analysis (Total, n=11687; new-developed AF, n=87), showing a high predictive capability (AUC = 0.887, p&lt;0.001). In this model, the relative contribution of parameters (by log likelihood) according to the time phase were P:40.8%, QRS:42.5%, and ST-T:24.9%, respectively (Figure B). Conclusions We determined ECG parameters that potentially contribute to picking up existing AF or predicting future development of AF, where the measurement of P wave strongly contributed in the former whereas all time phases were similarly important in the latter. Weighting of parameters to predict AF Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Self funding of the institute

Opportunistic screening for heart failure with natriuretic peptides in patients with atrial fibrillation: a meta-analysis of individual participant data of four screening studies

Heart ◽  
2018 ◽  
Vol 104 (15) ◽  
pp. 1236.1-1237 ◽  
Author(s):  
Sander van Doorn ◽  
Geert-Jan Geersing ◽  
Rogier F Kievit ◽  
Yvonne van Mourik ◽  
Loes C Bertens ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Meta Analysis ◽  
Diagnostic Value ◽  
Community Dwelling ◽  
Individual Participant Data ◽  
Cut Point ◽  
Individual Participant

ObjectiveHeart failure (HF) often coexists in atrial fibrillation (AF) but is frequently unrecognised due to overlapping symptomatology. Furthermore, AF can cause elevated natriuretic peptide levels, impairing its diagnostic value for HF detection. We aimed to assess the prevalence of previously unknown HF in community-dwelling patients with AF, and to determine the diagnostic value of the amino-terminal pro B-type natriuretic peptide (NTproBNP) for HF screening in patients with AF.MethodsIndividual participant data from four HF-screening studies in older community-dwelling persons were combined. Presence or absence of HF was in each study established by an expert panel following the criteria of the European Society of Cardiology. We performed a two-stage patient-level meta-analysis to calculate traditional diagnostic indices.ResultsOf the 1941 individuals included in the four studies, 196 (10.1%) had AF at baseline. HF was uncovered in 83 (43%) of these 196 patients with AF, versus 381 (19.7%) in those without AF at baseline. Median NTproBNP levels of patients with AF with and without HF were 744 pg/mL and 211 pg/mL, respectively. At the cut-point of 125 pg/mL, sensitivity was 93%, specificity 35%, and positive and negative predictive values 51% and 86%, respectively. Only 23% of all patients with AF had an NTproBNP level below the 125 pg/mL cut-point, with still a 13% prevalence of HF in this group.ConclusionsWith a prevalence of nearly 50%, unrecognised HF is common among community-dwelling patients with AF. Given the high prior change, natriuretic peptides are diagnostically not helpful, and straightforward echocardiography seems to be the preferred strategy for HF screening in patients with AF.

scholarly journals Evaluation of Total Adiponectin, Adipocyte Fatty Acid Binding Protein and Fibroblast Growth Factor 21 Levels in Individuals With Metabolic Syndrome

2014 ◽  
pp. 219-228 ◽  
Author(s):  
D. NOVOTNY ◽  
H. VAVERKOVA ◽  
D. KARASEK ◽  
J. LUKES ◽  
L. SLAVIK ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

Although many studies have investigated the relationships of several adipokines to metabolic syndrome (MetS), the interrelationships of adiponectin (ADP), adipocyte fatty acid binding protein (A-FABP) and fibroblast growth factor 21 (FGF 21) have not been described in detail. We examined 209 asymptomatic dyslipidemic patients divided into MetS+ (n=73) and MetS- (n=136) groups. The aim of study was to evaluate the relationships between observed adipokines, to compare the levels of total ADP, A-FABP and FGF 21 in individuals with and without MetS, and to elucidate the relationships of individual adipokines to lipid parameters, markers of insulin resistance and endothelial hemostatic markers in these groups. In MetS+ group, we found the independent positive association ADP with A-FABP (beta=0.4888, p=0.0382), A-FABP with FGF 21 (beta=0.3811, p=0.0002) and von Willebrand factor (beta=0.4502, p=0.0013), and FGF 21 with A-FABP (beta=0.4422, p=0.0002). Our study has confirmed the well-established risk profile of subjects with MetS, although clinically asymptomatic. MetS+ patients had also lower levels of ADP and higher levels of A-FABP and FGF 21. Our study evaluated the interrelationships of ADP, A-FABP and FGF 21 in asymptomatic dyslipidemic subjects with diagnosis of MetS. Especially strong association between A-FABP and FGF 21 needs to be clarified in further studies.

scholarly journals Clinical Significance of B-Type Natriuretic Peptide Levels at 3 Months after Atrial Fibrillation Ablation

Diseases ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 49
Author(s):  
Sen Matsumoto ◽  
Yasuharu Matsunaga-Lee ◽  
Masashi Ishimi ◽  
Mamoru Ohnishi ◽  
Nobutaka Masunaga ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Regression Analysis ◽  
Natriuretic Peptide ◽  
Roc Curve ◽  
Cox Regression ◽  
Significant Prognostic Factor ◽  
Cox Regression Analysis ◽  
Af Ablation ◽  
Increased Risk ◽  
The Impact

The role of B-type natriuretic peptide (BNP) levels as a predictor of arrhythmia recurrence (AR) after atrial fibrillation (AF) ablation remains unclear. In this study, we investigated the association of BNP levels before and 3 months after ablation with the risk of AR. A total of 234 patients undergoing their first session of AF ablation were included (68% male, mean age of 69 years). The cut-off value for discriminating AR was determined based on the maximum value of the area under the receiver operating characteristic (ROC) curve. The impact of BNP levels on AR was evaluated using Cox regression analysis. ROC curve analysis showed that the area under the curve for BNP at 3 months after the procedure was larger (0.714) compared to BNP levels before ablation (0.593). Elevated levels of BNP 3 months after the procedure (>40.5 pg/mL, n = 96) was associated with a higher risk of AR compared to those without elevated levels (34.4% vs. 10.9%, p < 0.01). Multivariate Cox regression analysis revealed that elevated BNP levels were associated with an increased risk of AR (hazard ratio 2.43; p = 0.014). Elevated BNP levels 3 months after AF ablation were a significant prognostic factor in AR, while baseline BNP levels were not.

scholarly journals Quantification of fibroblast growth factor 23 and N-terminal pro-B-type natriuretic peptide to identify patients with atrial fibrillation using a high-throughput platform: A validation study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (2) ◽  
pp. e1003405
Author(s):  
Winnie Chua ◽  
Jonathan P. Law ◽  
Victor R. Cardoso ◽  
Yanish Purmah ◽  
Georgiana Neculau ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Natriuretic Peptide ◽  
High Throughput ◽  
Fibroblast Growth Factor 23 ◽  
High Sensitivity ◽  
Fibroblast Growth ◽  
C Statistic

Background Large-scale screening for atrial fibrillation (AF) requires reliable methods to identify at-risk populations. Using an experimental semi-quantitative biomarker assay, B-type natriuretic peptide (BNP) and fibroblast growth factor 23 (FGF23) were recently identified as the most suitable biomarkers for detecting AF in combination with simple morphometric parameters (age, sex, and body mass index [BMI]). In this study, we validated the AF model using standardised, high-throughput, high-sensitivity biomarker assays. Methods and findings For this study, 1,625 consecutive patients with either (1) diagnosed AF or (2) sinus rhythm with CHA2DS2-VASc score of 2 or more were recruited from a large teaching hospital in Birmingham, West Midlands, UK, between September 2014 and February 2018. Seven-day ambulatory ECG monitoring excluded silent AF. Patients with tachyarrhythmias apart from AF and incomplete cases were excluded. AF was diagnosed according to current clinical guidelines and confirmed by ECG. We developed a high-throughput, high-sensitivity assay for FGF23, quantified plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and FGF23, and compared results to the previously used multibiomarker research assay. Data were fitted to the previously derived model, adjusting for differences in measurement platforms and known confounders (heart failure and chronic kidney disease). In 1,084 patients (46% with AF; median [Q1, Q3] age 70 [60, 78] years, median [Q1, Q3] BMI 28.8 [25.1, 32.8] kg/m2, 59% males), patients with AF had higher concentrations of NT-proBNP (median [Q1, Q3] per 100 pg/ml: with AF 12.00 [4.19, 30.15], without AF 4.25 [1.17, 15.70]; p < 0.001) and FGF23 (median [Q1, Q3] per 100 pg/ml: with AF 1.93 [1.30, 4.16], without AF 1.55 [1.04, 2.62]; p < 0.001). Univariate associations remained after adjusting for heart failure and estimated glomerular filtration rate, known confounders of NT-proBNP and FGF23. The fitted model yielded a C-statistic of 0.688 (95% CI 0.656, 0.719), almost identical to that of the derived model (C-statistic 0.691; 95% CI 0.638, 0.744). The key limitation is that this validation was performed in a cohort that is very similar demographically to the one used in model development, calling for further external validation. Conclusions Age, sex, and BMI combined with elevated NT-proBNP and elevated FGF23, quantified on a high-throughput platform, reliably identify patients with AF. Trial registration Registry IRAS ID 97753 Health Research Authority (HRA), United Kingdom

scholarly journals Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories

2016 ◽  
Vol 44 (8) ◽  
pp. 1072-1083 ◽  
Author(s):  
Kyuri Kim ◽  
Naseem Chini ◽  
David G. Fairchild ◽  
Steven K. Engle ◽  
William J. Reagan ◽  
...  
Keyword(s):  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Fatty Acid Binding Protein ◽  
Cardiac Toxicity ◽  
Myocardial Tissue ◽  
Fatty Acid Binding ◽  
Prognostic Accuracy ◽  
Toxicity Biomarkers ◽  
Myocardial Degeneration ◽  
Highly Correlated

There is a great need for improved diagnostic and prognostic accuracy of potential cardiac toxicity in drug development. This study reports the evaluation of several commercially available biomarker kits by 3 institutions (SRI, Eli Lilly, and Pfizer) for the discrimination between myocardial degeneration/necrosis and cardiac hypertrophy as well as the assessment of the interlaboratory and interplatform variation in results. Serum concentrations of natriuretic peptides (N-terminal pro-atrial natriuretic peptide [NT-proANP] and N-terminal pro-brain natriuretic peptide [NT-proBNP]), cardiac and skeletal troponins (cTnI, cTnT, and sTnI), myosin light chain 3 (Myl3), and fatty acid binding protein 3 (FABP3) were assessed in rats treated with minoxidil (MNX) and isoproterenol (ISO). MNX caused increased heart-to-body weight ratios and prominent elevations in NT-proANP and NT-proBNP concentrations detected at 24-hr postdose without elevation in troponins, Myl3, or FABP3 and with no abnormal histopathological findings. ISO caused ventricular leukocyte infiltration, myocyte fibrosis, and necrosis with increased concentrations of the natriuretic peptides, cardiac troponins, and Myl3. These results reinforce the advantages of a multimarker strategy in elucidating the underlying cause of cardiac insult and detecting myocardial tissue damage at 24-hr posttreatment. The interlaboratory and interplatform comparison analyses also showed that the data obtained from different laboratories and platforms are highly correlated and reproducible, making these biomarkers widely applicable in preclinical studies.

Natriuretic peptides inhibit rat astroglial proliferation: mediation by C receptor

1991 ◽  
Vol 261 (2) ◽  
pp. R453-R457 ◽  
Author(s):  
E. R. Levin ◽  
H. J. Frank
Keyword(s):  
Growth Factor ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Thymidine Incorporation ◽  
Primary Cultures ◽  
Physiological Role ◽  
Brain Cell ◽  
Bovine Brain ◽  
High Affinity ◽  
Capillary Endothelial Cells

The processing and secretion of atrial natriuretic peptide (ANP) from neurons and the expression of high-affinity receptors on astroglia from primary cultures of fetal rat diencephalon have recently been demonstrated. Thus natriuretic peptides may play a role in neuronal-glial signaling, but a physiological role has not been characterized. In these studies, we show that ANP and brain natriuretic peptide significantly (P less than 0.05) decrease the incorporation of [3H]thymidine into astroglia in the presence of fetal bovine serum and inhibit the proliferation of these cells in the presence or absence of serum. These effects were evident at concentrations of natriuretic peptides (10(-10) M) characteristic of the receptor Kd and were not seen in cultured bovine brain capillary endothelial cells, another brain cell expressing high-affinity receptors for the natriuretic peptides. The antiproliferative effects were potently produced by ANP-(4-23), a ring-deleted analogue of ANP-(1-28), which at the concentrations used in this study binds only to the C or low-molecular-weight natriuretic peptide receptor. Thymidine incorporation was not affected by adenosine 3',5'-cyclic monophosphate (cAMP), the inhibition of which has been proposed to mediate postbinding signaling of the C receptor. Epidermal growth factor (10(-9) M) produced an 87% increase in thymidine incorporation, which was not significantly inhibited by either form of ANP. Thus natriuretic peptides in the brain may serve as antigrowth factors for glia through binding to a receptor previously felt to function solely in peptide clearance. The inhibitory effects are not the result of inhibiting the proliferative effects of an endogenous growth factor and are cAMP independent.

scholarly journals Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort

EP Europace ◽  
2020 ◽  
Vol 22 (10) ◽  
pp. 1463-1469
Author(s):  
Bastiaan Geelhoed ◽  
Christin S Börschel ◽  
Teemu Niiranen ◽  
Tarja Palosaari ◽  
Aki S Havulinna ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Causal Relationship ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Mendelian Randomization ◽  
Causal Relation ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
Polygenic Risk

Abstract Aims Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and previous studies several single-nucleotide polymorphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. We investigated the causal relationship between natriuretic peptides and AF as well as HF using a Mendelian randomization approach. Methods and results N-terminal pro B-type natriuretic peptide (NT-proBNP) (N = 6669), B-type natriuretic peptide (BNP) (N = 6674), and mid-regional pro atrial natriuretic peptide (MR-proANP) (N = 6813) were measured in the FINRISK 1997 cohort. N = 30 common SNPs related to NT-proBNP, BNP, and MR-proANP were selected from studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF, separately. Polygenic risk scores (PRSs) based on multiple SNPs were used as genetic instrumental variable in Mendelian randomizations. Polygenic risk scores were significantly associated with the three natriuretic peptides. Polygenic risk scores were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation except for small causal betas is unlikely. Conclusion In our Mendelian randomization approach, we confirmed an association between common genetic variation at the NPPA-NPPB locus and natriuretic peptides. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF at the community-level was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms.

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