scholarly journals Dynamic risk stratification using serial measurements of plasma concentrations of natriuretic peptides in patients with heart failure

2018 ◽  
Vol 269 ◽  
pp. 196-200 ◽  
Author(s):  
J. Zhang ◽  
P. Pellicori ◽  
D. Pan ◽  
R. Dierckx ◽  
A.L. Clark ◽  
...  
Keyword(s):  
Heart Failure ◽  
Risk Stratification ◽  
Natriuretic Peptides ◽  
Plasma Concentrations ◽  
Dynamic Risk ◽  
Patients With Heart Failure ◽  
Serial Measurements

150 ProBNP glycosylation of threonine 71 is increased with obesity in patients with heart failure

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
L Lewis ◽  
S D Raudsepp ◽  
T G Yandle ◽  
C M Frampton ◽  
A M Richards ◽  
...  
Keyword(s):  
Heart Failure ◽  
Natriuretic Peptides ◽  
Diagnostic Performance ◽  
Plasma Concentrations ◽  
Amino Terminal ◽  
Patients With Heart Failure ◽  
National Heart Foundation ◽  
First Time ◽  
The Relationship ◽  
Heart Foundation

Abstract Funding Acknowledgements The National Heart Foundation of New Zealand Background Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Plasma levels of B-type natriuretic peptide (BNP) or its amino terminal congener (NT-proBNP) are used for HF diagnosis and risk stratification.  Circulating levels of both BNP and NT-proBNP are reduced by obesity and this phenomenon is one of the key weaknesses of the diagnostic performance of the natriuretic peptides in HF.  Formation of BNP from enzymatic cleavage of proBNP1-108 between residues 76 and 77 by corin and/or furin is influenced by the degree of proBNP glycosylation, therefore we investigated the relationship between proBNP glycosylation, plasma NT-proBNP and body mass index (BMI) in HF patients. Methods Three assays were developed to distinguish between total proBNP (glycosylated plus non-glycosylated proBNP), proBNP not glycosylated at threonine 71 (NG-T71) and proBNP not glycosylated in the central region (NG-C). Intra and inter-assay CVs were <15%, limits of detection were <2 pmol/L and samples diluted in parallel. Results Applying these assays and an NT-proBNP assay to plasma samples from 106 healthy volunteers and 238 patients with HF determined that concentrations (median(IQR)) of proBNP, NG-T71 and NT-proBNP were greater in HF patients compared to controls (24.9 (3.6-55), 9.4 (1.5-21) and 212 (104-409) pmol/L vs 3.0 (1.5-19), 3.0 (1.5-14.5) and 4.7 (2-8) pmol/L respectively, all p < 0.012).  NG-C was undetectable in most samples. ProBNP levels in HF patients with BMI above and below 30 kg/m2 were not different (21.9 (2.6-70) pmol/L and 25.7 (3.9-53) pmol/L respectively, p = 0.85), whereas HF patients with BMI > 30 had lower NT-proBNP and NG-T71 levels (121 (64-248) and 3 (1.5-16) pmol/L verse 271 (178-486) and 13.5 (1.5-24.2) pmol/L respectively, p < 0.003) and higher proBNP:NT-proBNP and proBNP:NG-T71 ratios  (p = 0.001 and p = 0.02 respectively) than those with BMI < 30. Discussion and Conclusion Using three new assays specific for different glycosylated forms of proBNP we have shown that the processing of proBNP is dysregulated in heart failure compared to controls due to increased glycosylation at threonine 71 of proBNP.  Obese patients with HF have even greater dysregulation, demonstrated by decreased concentrations of proBNP that is not glycosylated at T71 (NG-T71), and concomitant decreases in NT-proBNP.  Thus, we have shown for the first time that increased BMI is associated with increased proBNP glycosylation at T71 in patients with heart failure.  Glycosylation-induced impairment of proBNP processing explains, at least in part, the reduction in plasma concentrations of B-type cardiac natriuretic peptides observed in obesity. Using these assays to evaluate the proBNP profile of larger patient cohorts will further develop understanding of the relationships between BNP production, BMI and heart failure pathogenesis, which would be expected to lead to increased diagnostic performance.

scholarly journals ProBNP That Is Not Glycosylated at Threonine 71 Is Decreased with Obesity in Patients with Heart Failure

2019 ◽  
Vol 65 (9) ◽  
pp. 1115-1124 ◽  
Author(s):  
Lynley K Lewis ◽  
Sara D Raudsepp ◽  
Timothy C R Prickett ◽  
Timothy G Yandle ◽  
Robert N Doughty ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Mass Index ◽  
Risk Stratification ◽  
Central Region ◽  
Plasma Concentrations ◽  
Obese Patients ◽  
Plasma Samples ◽  
Amino Terminal ◽  
Patients With Heart Failure ◽  
The Relationship

Abstract BACKGROUND Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Plasma concentrations of B-type natriuretic peptide (BNP) or its amino terminal congener (NT-proBNP) are used for HF diagnosis and risk stratification. Because BNP concentrations are inexplicably lowered in obese patients, we investigated the relationship between proBNP glycosylation, plasma NT-proBNP, and body mass index (BMI) in HF patients. METHODS Three assays were developed to distinguish between total proBNP (glycosylated plus nonglycosylated proBNP), proBNP not glycosylated at threonine 71 (NG-T71), and proBNP not glycosylated in the central region (NG-C). Intraassay and interassay CVs were <15%; limits of detection were <21 ng/L; and samples diluted in parallel. RESULT Applying these assays and an NT-proBNP assay to plasma samples from 106 healthy volunteers and 238 HF patients determined that concentrations [median (interquartile range)] of proBNP, NG-T71, and NT-proBNP were greater in HF patients compared with controls [300 (44–664), 114 (18–254), and 179 (880–3459) ng/L vs 36 (18–229), 36 (18–175), and 40 (17–68) ng/L, respectively; all P < 0.012]. NG-C was undetectable in most samples. ProBNP concentrations in HF patients with BMI more or less than 30 kg/m2 were not different (P = 0.85), whereas HF patients with BMI >30 kg/m2 had lower NT-proBNP and NG-T71 concentrations (P < 0.003) and higher proBNP/NT-proBNP and proBNP/NG-T71 ratios (P = 0.001 and P = 0.02, respectively) than those with BMI <30 kg/m2. CONCLUSIONS Increased BMI is associated with decreased concentrations of proBNP not glycosylated at T71. Decreased proBNP substrate amenable to processing could partially explain the lower NT-proBNP and BNP concentrations observed in obese individuals, including those presenting with HF.

scholarly journals Heart Failure and Diabetes Mellitus: Biomarkers in Risk Stratification and Prognostication

2021 ◽  
Vol 11 (10) ◽  
pp. 4397
Author(s):  
Michael Lichtenauer ◽  
Peter Jirak ◽  
Vera Paar ◽  
Brigitte Sipos ◽  
Kristen Kopp ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Risk Stratification ◽  
Natriuretic Peptides ◽  
Predictive Ability ◽  
High Sensitivity ◽  
Routine Practice ◽  
Reduced Ejection Fraction ◽  
Novel Biomarkers

Heart failure (HF) and type 2 diabetes mellitus (T2DM) have a synergistic effect on cardiovascular (CV) morbidity and mortality in patients with established CV disease (CVD). The aim of this review is to summarize the knowledge regarding the discriminative abilities of conventional and novel biomarkers in T2DM patients with established HF or at higher risk of developing HF. While conventional biomarkers, such as natriuretic peptides and high-sensitivity troponins demonstrate high predictive ability in HF with reduced ejection fraction (HFrEF), this is not the case for HF with preserved ejection fraction (HFpEF). HFpEF is a heterogeneous disease with a high variability of CVD and conventional risk factors including T2DM, hypertension, renal disease, older age, and female sex; therefore, the extrapolation of predictive abilities of traditional biomarkers on this population is constrained. New biomarker-based approaches are disputed to be sufficient for improving risk stratification and the prediction of poor clinical outcomes in patients with HFpEF. Novel biomarkers of biomechanical stress, fibrosis, inflammation, oxidative stress, and collagen turn-over have shown potential benefits in determining prognosis in T2DM patients with HF regardless of natriuretic peptides, but their role in point-to-care and in routine practice requires elucidation in large clinical trials.

Management of Oral Anti-Coagulation in Patients with Heart Failure—Insights from the ThrombEVAL Study

2018 ◽  
Vol 118 (11) ◽  
pp. 1930-1939
Author(s):  
Sebastian Göbel ◽  
Jürgen Prochaska ◽  
Lisa Eggebrecht ◽  
Ronja Schmitz ◽  
Claus Jünger ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adverse Events ◽  
Vitamin K Antagonists ◽  
Plasma Concentrations ◽  
Regular Care ◽  
Increased Risk ◽  
Patients With Heart Failure ◽  
Specialized Care ◽  
The Impact

AbstractPatients with heart failure (HF) are frequently anti-coagulated with vitamin K-antagonists (VKAs). The use of long-acting VKA may be preferable for HF patients due to higher stability of plasma concentrations. However, evidence on phenprocoumon-based oral anti-coagulation (OAC) therapy in HF is scarce. The aim of this study was to assess the impact of the presence of HF on quality of phenprocoumon-based OAC and the subsequent clinical outcome. Quality of OAC therapy and the incidence of adverse events were analysed in a cohort of regular care (n = 2,011) from the multi-centre thrombEVAL study program (NCT01809015) stratified by the presence of HF. To assess the modifiability of outcome, results were compared with data from individuals receiving specialized care for anti-coagulation (n = 760). Overall, the sample comprised of 813 individuals with HF and 1,160 subjects without HF in the regular care cohort. Quality of OAC assessed by time in therapeutic range (TTR) was 66.1% (47.8%/82.8%) for patients with HF and 70.6% (52.1%/85.9%) for those without HF (p = 0.0046). Stratification for New York Heart Classification (NYHA)-class demonstrated a lower TTR with higher NYHA classes: TTRNYHA-I 69.6% (49.4%/85.6%), TTRNYHA-II 66.5% (50.1%/82.9%) and TTRNYHA-≥III 61.8% (43.1%/79.9%). This translated into a worse net clinical benefit outcome for HF (hazard ratio [HR] 1.63 [1.31/2.02]; p < 0.0001) and an increased risk of bleeding (HR 1.40 [1.04/1.89]; p = 0.028). Management in a specialized coagulation service resulted in an improvement of all, TTR (∆+12.5% points), anti-coagulation-specific and non-specific outcome of HF individuals. In conclusion, HF is an independent risk factor for low quality of OAC therapy translating into an increased risk for adverse events, which can be mitigated by specialized care.

Abstract 5920: Usefulness of Late Gadolinium Enhancement as Non-invasive Arrhythmic Risk Marker in Patients with Heart Failure and Systolic Dysfunction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Alfonso Valle ◽  
Mercedes Nadal ◽  
Jordi Estornell ◽  
Nieves Martinez ◽  
Miguel Corbi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Late Gadolinium Enhancement ◽  
Risk Stratification ◽  
Systolic Dysfunction ◽  
Total Mortality ◽  
Left Ventricular ◽  
Gadolinium Enhancement ◽  
Non Invasive ◽  
Patients With Heart Failure

The identification of prognostic markers in patients with heart failure of both ischemic and non ischemic etiology is an increasing need in the era of devices therapy. Risk stratification for sudden cardiac death (SCD) remains problematic with reliance on left ventricular function which predicts total mortality rather than arrhythmic events (AE). Recently cardiac magnetic resonance was employed to predict susceptibility for malignant arrhythmias. This study sought to determine the utility of late gadolinium enhancement (LGE) to predict AE. Three hundred consecutive patients with symptomatic heart failure and systolic dysfunction of both ischemic and non ischemic cause undergoing CMR, were classified into two groups attending to the presence (n 160) or absence of LGE (n 140), and were followed prospectively during 842 days. The primary endpoint was the combined of SCD or Ventricular tachycardia (VT). 23 patients had AE (8 SCD/15 VT) during the follow-up, 19 of them presenting LGE (83%). The presence of LGE was associated to a significantly higher AE rate (11.8.% vs 2.8% p< 0.001)(figure ). Compared to patients without LGE, midwall fibrosis and an ischemic pattern of LGE predicted AE. (3% vs 5% vs 14%, p= 0.001) LGE is a new non-invasive predictor of AE in patients with heart failure and systolic dysfunction. This suggest a potential role for risk stratification and better selection of patients who needs device therapy

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