Biomarkers in acutely decompensated heart failure with preserved or reduced ejection fraction
ABSTRACT Acute decompensated heart failure (ADHF) occurs with preserved (heart failure with preserved ejection fraction [HFpEF] ≥50%) or reduced (heart failure with reduced ejection fraction [HFrEF] <50%) ejection fraction. Natriuretic peptide (NP) levels are lower in HFpEF than HFrEF. We hypothesized that lower NP levels in HFpEF may be associated with other differences in biomarkers, specifically, renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress, and a biomarker that reflects collagen synthesis.
In this prespecified ancillary analysis of patients with ADHF enrolled in the Diuretic Optimization Strategies Evaluation study, clinical features and N-terminal pro-B-type NP, cystatin C, plasma renin activity, aldosterone, oxidative stress (uric acid), and procollagen type III N-terminal peptide were compared in HFpEF and HFrEF at enrollment and 60-day follow-up.
Compared with HFrEF (n = 219), HFpEF (n = 81) patients were older, heavier, more commonly female, less treated with RAAS antagonists, but with similar New York Heart Association class, jugular venous pressure, and edema severity. N-terminal pro-B-type NP was lower, and systolic blood pressure and cystatin C were higher in HFpEF. Despite higher systolic blood pressure and less RAAS antagonist use in HFpEF, plasma renin activity and aldosterone levels were similar in HFpEF and HFrEF as were uric acid and procollagen type III N-terminal peptide levels. Changes in biomarker levels from enrollment to 60 days were similar between HFrEF (n = 149) and HFpEF (n = 50).
Lower NP levels in decompensated HFpEF occur in association with similar ADHF severity, more impaired vascular and renal function but similar elevation of biomarkers that reflect RAAS activation, oxidative stress, and collagen synthesis as in HFrEF.
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ABSTRACT: Background: Heart failure (HF) is a growing public health problem. Patients often present to emergency department (ED) with acute onset dyspnea where a rapid triage is required to avoid misdiagnosis and to institute appropriate therapy. An objective risk-stratification in the ED is warranted to identify patients at high risk of adverse outcomes, so that more intensive therapy and vigilant follow-up after discharge are instituted. Methods and Results: Fifty two consecutive acute HF (AHF) patients in NYHA class III/IV were enrolled for the present study. N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hsTropT), high-sensitivity C-reactive protein (hsCRP) and Uric acid (UA) were evaluated at admission; a second sample for NT-proBNP and hsTropT was obtained 48h later. The end-point of the study, a composite of cardiovascular death, rehospitalisation for worsening HF symptoms and refractory HF was reached in 32.7% of patients during a median follow-up of 4.8mnth. Although, hsTropT (>0.014ng/ml), hsCRP (>0.5mg/dl) and UA (>5.6mg/dl for females and >7 mg/dl for males) were elevated in the vast majority of patients (92.3%, 75% and 63.5% respectively), baseline and changing patterns of NT-proBNP following treatment were the only predictors of adverse outcomes on follow-up. A significant correlation between hsTropT, hsCRP and UA was observed suggesting a link between inflammation, myocyte injury and oxidative stress in AHF. Conclusion: Baseline and changing patterns of NT-proBNP predicted adverse outcomes on follow-up suggesting that a strategy of serial measurement of NT-proBNP could prove invaluable in early risk stratification. Further research is needed to understand the link between inflammation, myocyte injury and oxidative stress in AHF which could provide potential therapeutic targets.Journal of Clinical and Diagnostic Research 09/2014; 8(9):MC01-MC06. DOI:10.7860/JCDR/2014/9289.4783 · 0.13 Impact Factor
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ABSTRACT: The paper is focused on the evaluation of the serum levels of matrix metalloproteinases (MMP -2, MMP -3, MMP - 9), tissue inhibitors (TIMP -1 and TIMP -2), natriuretic peptides, pusle wave velocity in patients (pts) with heart failure with preserved ejection fraction (HFpEF) in 12 month after ST elevation myocardial infarction (STEMI). The study included 55 pts. The serum levels of MMP -2, MMP -3, MMP - 9, the precursor of matrix metalloproteinase -1 (proMMP -1), TIMP -1 and TIMP -2, high-sensitivity C-reactive protein (hsCRP) were determined by ELISA. BNP in whole blood was determined on panels Triage BNP test. The most pts had class II NYHA (49%), as was often II class angina (53%). Increases in levels of BNP were dependent on class of NYHA. The stiffness of the great arteries was associated with increasing in BNP and NT-proBNP. There were no changes in levels of proMMP-1, MMP 3, MMP-2, MMP-9. But the serum levels of TIMP-1, hsCRP were increased in pts with HFpEF after STEMI. A positive relationship between hsCRP and TIMP-1 was obtained. Moreover, we found decreasing in levels of MMP-3 in pts with increased rigidity without the risk of cardiovascular events.Advanced Materials Research 01/2015; 1085:406-413. DOI:10.4028/www.scientific.net/AMR.1085.406
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ABSTRACT: Differentiation of heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction independent of echocardiography is challenging in the community. Diagnostic strategies based on monitoring circulating microRNA (miRNA) levels may prove to be of clinical value in the near future. The aim of this study was to identify a novel miRNA signature that could be a useful HF diagnostic tool and provide valuable clinical information on whether a patient has HFrEF or HFpEF. MiRNA biomarker discovery was carried out on three patient cohorts, no heart failure (no-HF), HFrEF, and HFpEF, using Taqman miRNA arrays. The top five miRNA candidates were selected based on differential expression in HFpEF and HFrEF (miR-30c, -146a, -221, -328, and -375), and their expression levels were also different between HF and no-HF. These selected miRNAs were further verified and validated in an independent cohort consisting of 225 patients. The discriminative value of BNP as a HF diagnostic could be improved by use in combination with any of the miRNA candidates alone or in a panel. Combinations of two or more miRNA candidates with BNP had the ability to improve significantly predictive models to distinguish HFpEF from HFrEF compared with using BNP alone (area under the receiver operating characteristic curve >0.82). This study has shown for the first time that various miRNA combinations are useful biomarkers for HF, and also in the differentiation of HFpEF from HFrEF. The utility of these biomarker combinations can be altered by inclusion of natriuretic peptide. MiRNA biomarkers may support diagnostic strategies in subpopulations of patients with HF. © 2015 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.European Journal of Heart Failure 03/2015; DOI:10.1002/ejhf.244 · 6.58 Impact Factor