Biomarkers In Heart Failure Patients Research Articles

Neopterin as a Potential Biomarker for the Early Diagnosis of Heart Failure: A Systematic Review and Meta-analysis.

Neopterin (NEO) is an inflammatory biomarker with proposed diagnostic value in cardiovascular diseases. Some correlations have been discovered between NEO levels and the incidence, severity, and adverse outcomes of heart failure (HF). However, there are discrepancies in the results reported in the literature. We conducted a systematic review and meta-analysis of studies comparing urinary and blood NEO concentrations between individuals with HF, cardiac insufficiency, or dilated cardiomyopathy (DCM) with control groups or those monitoring the role of NEO concentrations as a predictive marker of adverse outcomes in HF patients. A total of 24 studies that met the inclusion criteria were reviewed. The studies demonstrated the alteration of NEO in blood or urine samples in subjects with HF, cardiac insufficiency, or DCM compared with control groups. Also, reviewing the studies suggested a link between reduced ejection fraction, higher NYHA classes, and a higher risk of adverse cardiac outcomes with increased NEO levels. The meta-analysis of three studies revealed a significant increase in serum NEO levels in HF cases compared to that in healthy controls with an effect size of 3.72 (95 % CI 0.16 to 7.28; p = 0.04). Meta-analysis demonstrated a significant difference between serum NEO levels of HF cases and healthy subjects. This evidence implies the potential of serum NEO as a valuable diagnostic biomarker in HF patients. Also, the review of the studies revealed the prognostic potential of NEO. Further research is required to assess the usefulness of NEO as a diagnostic/prognostic biomarker for HF.

The prognostic impact of inflammation in patients with decompensated acute heart failure, as assessed using the pan-immune inflammation value (PIV)

There is increasing evidence that composite scores based on blood counts, which are reflectors of uncontrolled inflammation in the development and progression of heart failure, can be used as prognostic biomarkers in heart failure patients. The prognostic effects of pan-immune inflammation (PIV) as an independent predictor of in-hospital mortality in patients with acute heart failure (AHF) were evaluated based on this evidence. The data of 640 consecutive patients hospitalized for New York Heart Association (NYHA) class 2-3-4 AHF with reduced ejection fraction were analyzed and 565 patients were included after exclusion. The primary outcome was in hospital all-cause death. Secondary outcomes were defined as the following in-hospital events: Acute kidney injury (AKI), malignant arrhythmias, acute renal failure (ARF) and stroke. The PIV was computed using hemogram parameters such as lymphocytes, neutrophils, monocytes and platelets. Patients were categorized as low or high PIV group according to the median value, which was 382.8. A total of 81 (14.3%) in-hospital deaths, 31 (5.4%) AKI, 34 (6%) malignant arrhythmias, 60 (10.6%) ARF and 11 (2%) strokes were reported. Patients with high PIV had a higher in-hospital mortality rate than patients with low PIV (OR: 1.51, 95% CI, 1.26-1.80, p < 0.001). Incorporating PIV into the full model significantly improved model performance (odds ratio X2, p < 0.001) compared to the baseline model constructed with other inflammatory markers. PIV is a potent predictor of prognosis with better performance than other well-known inflammatory markers for patients with AHF.

PACAP-38 and PAC1 Receptor Alterations in Plasma and Cardiac Tissue Samples of Heart Failure Patients.

Pituitary adenylate cyclase activating polypeptide-38 (PACAP-38) is a multifunctional neuropeptide, which may play a role in cardioprotection. However, little is known about the presence of PACAP-38 in heart failure (HF) patients. The aim of our study was to measure the alterations of PACAP-38 like immunoreactivity (LI) in acute (n = 13) and chronic HF (n = 33) and to examine potential correlations between PACAP-38 and HF predictors (cytokines, NT-proBNP). Tissue PACAP-38 LI and PAC1 receptor levels were also investigated in heart tissue samples of patients with HF. Significantly higher plasma PACAP-38 LI was detected in patients with acute HF, while in chronic HF patients, a lower level of immunoreactivity was observed compared to healthy controls (n = 13). Strong negative correlation was identified between plasma PACAP-38 and NT-proBNP levels in chronic HF, as opposed to the positive connection seen in the acute HF group. Plasma IL-1 β, IL-2 and IL-4 levels were significantly lower in chronic HF, and IL-10 was significantly higher in patients with acute HF. PACAP-38 levels of myocardial tissues were lower in all end-stage HF patients and lower PAC1 receptor levels were detected in the primary dilated cardiomyopathy group compared to the controls. We conclude that PACAP-38 and PAC1 expression correlates with some biomarkers of acute and chronic HF; therefore, further studies are necessary to explore whether PACAP could be a suitable prognostic biomarker in HF patients.

Prognostic utility of soluble ST2 biomarker in heart failure patients with reduced ejection fraction

sST2 is a member of interleukin 1 receptor family biomarker and the concentration of its soluble isoform increases with cardiac stress leading to cardiac fibrosis. It has 2 isoforms the ligand forms sST2L and soluble form. In acute or chronic heart failure the soluble form is highly prognostic and predictive of mortality. It’s a prospective study of patients aged 45 to 90 with reduced ejection fraction and cardiomyopathy. Sample collected for day 1,5,30. There outcome assessed at day 30 and mortality on one year follow up. Total 79 patients studied, 57 LVF cases and 22 healthy controls. 50 males, 29 females, Cardiomyopathy 24 cases. Mean sST2 value 137.7829±89 (SD). At 30 days outcome and one year mortality with significant P value 0.000. As the age increases sST2 levels rises. For cardiomyopathy patients sST2 (141±78). At day 5 and 30 patients improved with decrease in levels where worsened patients had persistent high values. Those patient with more than 250 or implausible values had worse outcome or expired. Most important those responded to appropriate treatment values significantly improved. For cardiomyopathy patients values remained high persistently and ultimately required cardiac transplant or definitive line of treatment. sST2 is diagnostic and prognostic marker in patients with HFrEF presenting as acute or chronic heart failure. Significant p values for 30 days outcome and mortality. In cardiomyopathy patients with persistent high levels were bad prognostic indicator and suggests consideration of definitive line of treatment.

Identification of CALU and PALLD as Potential Biomarkers Associated With Immune Infiltration in Heart Failure.

Background: Inflammatory activation and immune infiltration play important roles in the pathologic process of heart failure (HF). The current study is designed to investigate the immune infiltration and identify related biomarkers in heart failure patients due to ischemic cardiomyopathy.Methods: Expression data of HF due to ischemic cardiomyopathy (CM) samples and non-heart failure (NF) samples were downloaded from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between CM and NF samples were identified. Single sample gene set enrichment analysis (ssGSEA) was performed to explore the landscape of immune infiltration. Weighted gene co-expression network analysis (WGCNA) was applied to screen the most relevant module associated with immune infiltration. The diagnostic values of candidate genes were evaluated by receiver operating curves (ROC) curves. The mRNA levels of potential biomarkers in the peripheral blood mononuclear cells (PBMCs) isolated from 10 CM patients and 10 NF patients were analyzed to further assess their diagnostic values.Results: A total of 224 DEGs were identified between CM and NF samples in GSE5406, which are mainly enriched in the protein processing and extracellular matrix related biological processes and pathways. The result of ssGSEA showed that the abundance of dendritic cells (DC), mast cells, natural killer (NK) CD56dim cells, T cells, T follicular helper cells (Tfh), gammadelta T cells (Tgd) and T helper 2 (Th2) cells were significantly higher, while the infiltration of eosinophils and central memory T cells (Tcm) were lower in CM samples compared to NF ones. Correlation analysis revealed that Calumenin (CALU) and palladin (PALLD) were negatively correlated with the abundance of DC, NK CD56dim cells, T cells, Tfh, Tgd and Th2 cells, but positively correlated with the level of Tcm. More importantly, CALU and PALLD were significantly lower in PBMCs from CM patients compared to NF ones.Conclusion: Our study revealed that CALU and PALLD are potential biomarkers associated with immune infiltration in heart failure due to ischemic cardiomyopathy.

Breath acetone concentration: too heterogeneous to constitute a diagnosis or prognosis biomarker in heart failure? A systematic review and meta-analysis

Introduction. Exhaled breath acetone (ExA) has been investigated as a biomarker for heart failure (HF). Yet, barriers to its use in the clinical field have not been identified. The aim of this systematic review and meta-analysis was to assess the ExA heterogeneity and factors of variability in healthy controls (HC), to identify its relations with HF diagnosis and prognostic factors and to assess its diagnosis and prognosis accuracy in HF patients. Methods. A systematic search was conducted in PUBMED and Web of Science database. All studies with HC and HF patients with a measured ExA were included and studies providing ExA’s diagnosis and prognosis accuracy were identified. Results. Out of 971 identified studies, 18 studies involving 833 HC and 1009 HF patients were included in the meta-analysis. In HC, ExA showed an important heterogeneity (I 2 = 99%). Variability factors were fasting state, sampling type and analytical method. The mean ExA was 1.89 times higher in HF patients vs. HC (782 [531–1032] vs. 413 [347–478] ppbv; p < 0.001). One study showed excellent diagnosis accuracy, and one showed a good prognosis value. ExA correlated with New York Heart Association (NYHA) dyspnea (p < 0.001) and plasma brain natriuretic peptide (p < 0.001). Studies showed a poor definition and reporting of included subjects. Discussion. Despite the between-study heterogeneity in HC, the evidence of an excellent diagnosis and prognosis value of ExA in HF from single studies can be extended to clinical populations worldwide. Factors of variability (ExA procedure and breath sampling) could further improve the diagnosis and prognosis values of this biomarker in HF patients.

Prognostic value of soluble ST2 biomarker in heart failure patients with obstructive sleep apnea syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Objective. To analyze the relationships between soluble ST2 (sST2) levels, apnea/hypopnea index (AHI) and echocardiographic parameters in heart failure patients with preserved ejection fraction (HFpEF) and to evaluate prognostic values of sST2 in the development of adverse cardiac events (ASE) during the 12-month follow-up period. Methods. A total of 86 men, median age of 62.0 (41.0; 78.0) years with obstructive sleep apnea syndrome (OSAS) and HF of NYHA class I-III with baseline LVEF of 60% [52; 65]% were enrolled in the study. The severity of obstructive breathing disorders during sleep was assessed by AHI. Serum levels of NT-proBNP and sST2 were measured using ELISA at baseline. Two-dimensional transthoracic echocardiography with assessment of right ventricular (RV) function and 6-minute walk test (6MWT) were performed at baseline. Results. The values of AHI significantly correlated with body mass index (r = 0.362), left atrial volume (r = 0.570), fractional change in the area of the RV (r=-0.527), RV myocardial function index (r=-0.377), NT-proBNP (r = 0.611), 6MWT (r=-0.511), RV anterior wall thickness (r = 0,472), while the levels of sST2 significantly correlated with LV remodeling parameters: LVEF (r =-0.301), end-systolic volume (r =0.453), end-diastolic volume (r =0.396), end-systolic dimension (r = 0.373), end-diastolic dimension (r =0.288). Based on ROC-analysis, sST2 ≥29.67 ng/mL (sensitivity 63.6%, specificity 73.6%, AUC = 0.645; p &amp;lt; 0.0001) were identified as a cut-off values predicting the development of ACE. At 12 months of follow-up period all patients were divided into 2 groups according to cut-off values of sST2: group 1 (n = 29) comprised patients with sST2 ≥29.67 ng/mL, group 2 (n = 42) comprised patients with sST2 &amp;lt;29.67 ng/mL. The median baseline values of sST2 were 41.39 [33.31; 50.99] ng/mL in group 1, and 22.18 [20.64; 25.5] ng/mL in group 2. The concentrations of NT-proBNP did not differ between the groups. During the 12-month follow-up period in group 1 the rate of ACE was 29.7% cases, and 5.2% in group 2, respectively. According to Kaplan-Meier analysis, a higher sST2 levels was associated with a higher frequency of ACE during 12 months of follow-up (р&amp;lt;0.0001). Univariable and multivariable Cox regression analyses showed sST2 concentrations were significantly associated with ACE (odds ratio 2.25, 95%CI: 2.06 to 3.29, p &amp;lt; 0.001), when adding AHI and LV myocardial mass index improved reclassification of risk stratification (odds ratio 3,28, 95%CI: 3,09 to 4,49, p &amp;lt; 0.001, AUC of 0.945, percent of cases correctly classified of 90.14 %). However, NT-proBNP addition had a limited effect on risk stratification. Conclusion. Our data suggest that sST2 may be used as a diagnostic biomarker for prediction of ACE in patients with HFpEF and OSAS during the 12-month follow-up period. The combined evaluation of sST2, AHI and LV myocardial mass index values demonstrated higher diagnostic sensitivity and specificity for prediction of ACE.

Heart failure patients with implantable cardioverter-defibrillator: molecular predictors for risk assessment of adverse events

Abstract Funding Acknowledgements Type of funding sources: None. Objective. The objectives of the study were to evaluate a multimarker strategy including galectin-3, soluble ST2 (sST2) and NT-proBNP for risk stratification of adverse cardiovascular events (ACE) and death in heart failure (HF) patients with implantable cardioverter-defibrillator (ICD) during the 12-month follow-up period. Methods. A total of 57 patients (41 men, median age of 65 [59; 68] years) of New York Heart Association (NYHA) class II-IV and baseline LVEF of 34% [26; 44]% were enrolled in the study. 71% of patients had prior myocardial infarction and 86% received prior myocardial revascularization (coronary artery bypass graft/stent). Serum levels of sST2, NT-proBNP and galectin-3 were measured using an enzyme immunoassay at baseline. All patients received implantation of cardioverter-defibrillator. Results. After the 12-month follow-up period, all patients were divided into 2 groups: group A (n = 17) comprised patients with ASE, group B (n = 40) comprised those without it. During 12-month follow-up period 15.8% of patients (n = 9) died. The median values of sST2 in group A were higher (p = 0.001) by 51% than in group B (24.42 [22.46; 31.4] and 49.94 [37.4; 58.54] ng/mL, respectively). The median values of galectin-3 in group A (p = 0.002) were 14.7 [9.95; 24.3] ng/L and 9.2 [7.2; 14.7] ng/L in group B. The median values of NT-proBNP were also higher (p = 0.021) by 22% in patients with ASE. Odds ratio for hyperexpression of sST2 was 3.06 (95% CI 2.89-3.17; p &amp;lt;0.0001), 3.79 for galectin-3 (95% CI 2.67-4.11; p &amp;lt; 0.001), and 1.27 for NT-proBNP (95% CI 0.89-2.21; p = 0.036). Reclassification did not significantly benefit after NT-proBNP addition into the full model; some indices even worsened with all 3 biomarkers. Based on ROC-analysis, baseline sST2 concentration of 34.43 ng/mL (sensitivity of 86.7%, specificity of 71.9%, and AUC of 0.78; p &amp;lt; 0.0001) and baseline galectin-3 concentration of 11.6 ng/L (sensitivity of 67.5%, specificity of 70.6%, and AUC of 0.72; p = 0.0014) were identified as a cut-off values predicting adverse cardiac events. The combined evaluation of both biomarkers increased the predictive value of the analysis (sensitivity of 90.1%, specificity of 79.1%, and AUС of 0.84; p &amp;lt; 0.0001). Conclusion. Our data suggest that ST2 and galectin-3 may be used as diagnostic biomarkers in HF patients with ICD. The combined use of sST2 and galectin-3 demonstrated higher diagnostic sensitivity and specificity for prediction of adverse outcomes. However, NT-proBNP in addition to ST2 and galectin-3 biomarkers had a limited effect on risk stratification.

Reappraisal of Inflammatory Biomarkers in Heart Failure.

Inflammation has been shown to be an important factor in the development and progression of heart failure (HF), regardless of the etiology. There have been many studies that demonstrated roles of inflammatory biomarkers in diagnosis, prognosis of chronic and acute HF patients, and also markers of cardiotoxicity from chemotherapy. These cytokines are high-sensitivity C-reactive protein (hsCRP), myeloperoxidase (MPO), soluble growth stimulation expressed gene 2 (sST2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), growth differentiation factor-15 (GDF-15), endothelin-1 (ET-1), and galectin-3. In this review, we discuss the past and present insights of those inflammatory biomarkers in order to gain more understanding in pathogenesis of HF, risk stratification of HF patients, and early detection of cardiotoxicity from cancer therapy. Many inflammatory cytokines have been shown to be associated with mortality of both chronic and acute HF patients, and some of them are able to track treatment responses, especially sST2 and galectin-3, which are the only two inflammatory biomarkers recommended to use in clinical setting by the recent standard HF guidelines, while some studies described ET-1 and MPO as potential predictors of cardiotoxicity from cancer drugs. The prognostic implications of inflammatory biomarkers in HF patients have been demonstrated more consistently in chronic than acute HF, with some suggestions of ET-1 and MPO in patients receiving chemotherapy. However, further studies are necessary for the use of inflammatory biomarkers in routine clinical practice.

ENERGY LOSS BY VECTOR FLOW MAPPING IS ASSOCIATED WITH SYMPTOM SEVERITY AND SERUM BIOMARKERS IN HEART FAILURE PATIENTS WITH REDUCED EJECTION FRACTION

Vector flow mapping (VFM) can quantify left ventricular (LV) flow mechanics noninvasively. VFM can measure LV energy loss and pump efficiency. However, the association of LV energy loss to symptom severity and serum biomarkers in heart failure patients with reduced ejection fraction (HFrEF) is

Non-natriuretic peptide biomarkers in heart failure with preserved and reduced ejection fraction.

Heart failure (HF) with reduced and preserved ejection fraction constitutes two entities with distinct pathogenetic backgrounds sharing common features. Beyond natriuretic peptides, several novel biomarkers have been proven useful in the diagnosis, prognosis and treatment of HF. Biomarkers of myocardial fibrosis have a low diagnostic yield in subjects with acute HF but may add prognostic information, especially in patients with HF and preserved ejection fraction. Biomarkers of renal impairment identify subjects with worse prognosis independently of left ventricle ejection fraction while inflammatory markers have not been proven useful in patients with systolic or diastolic impairment. In this review article, we summarize the main differences and application of non-natriuretic peptide biomarkers in HF patients with preserved and reduced ejection fraction.

Examination of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) as a Potential Biomarker in Heart Failure Patients.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic and multifunctional neuropeptide having neurotrophic, neuroprotective, and general cytoprotective actions in a variety of tissues based on its anti-apoptotic, anti-inflammatory, and antioxidant effects. Several studies have demonstrated its cardioprotective effects in vitro and in various animal models. However, few data are available on the presence of PACAP in human cardiac tissues and its role in the pathomechanism and progression of different cardiac disorders, particularly heart failure. Earlier, our research group has shown PAC1 receptor immunoreactivity in human heart tissue samples and we have found significantly elevated PACAP27- and PACAP38-like immunoreactivity in ischemic cardiac samples compared to valvular abnormalities with radioimmunoassay. In the last few years, numerous studies examined the presence and the changes of PACAP levels in different human tissue samples and biological fluids to show alterations in different physiological and pathological conditions. Therefore, the aim of the present study was to measure the alterations of blood PACAP levels in chronic heart failure caused by primary dilated cardiomyopathy or ischemic cardiomyopathy and to examine the possible relationship between serum levels of PACAP, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and systolic left ventricular function, the most reliable biomarkers of heart failure. In the group of mild heart failure patients, a significant strong negative correlation was detected. Furthermore, in moderate heart failure, we found a significant moderate negative correlation between PACAP and NT-proBNP levels only in ischemic subgroup. Positive correlation was found between serum PACAP level and ejection fraction only in patients with heart failure due to ischemic cardiomyopathy but not in patients with primary dilated cardiomyopathy. In summary, remarkable differences were observed between the ischemic and non-ischemic heart failure suggesting that PACAP might play an important role in the pathomechanism and progression of ischemic heart failure and it might be a potential biomarker of cardiac diseases in the future.

Elevated exhaled acetone concentration in stage C heart failure patients with diabetes mellitus

BackgroundBreath acetone is a noninvasive biomarker of heart failure; however, its significance in heart failure patients with diabetes mellitus has yet to be clarified. The objective of this study is to investigate whether exhaled acetone concentration is a noninvasive biomarker in heart failure patients with diabetes mellitus.MethodsThis study prospectively included 35 diabetic patients with stage C heart failure and 20 diabetic patients with or at risk of heart failure (stage A or B). Exhaled breath was collected after an overnight fast.ResultsThe stage C group had significantly higher brain natriuretic peptide levels, larger left ventricular diameter, lower left ventricular ejection fraction, and more frequent use of β-blocker, compared with the stage A or B group. The stage C group had higher exhaled acetone concentrations than the stage A or B group (p = 0.013). Exhaled acetone concentration was correlated with total ketone bodies (r = 0.588, p < 0.001) and brain natriuretic peptide (r = 0.415, p = 0.002).ConclusionStage C heart failure patients with diabetes mellitus have elevated exhaled acetone concentrations. Exhaled acetone concentration could be a noninvasive biomarker in heart failure patients with diabetes mellitus.

Regulation of circulating chromogranin B levels in heart failure

Background: Chromogranin B (CGB) regulates B-type natriuretic peptide (BNP) production. Circulating CGB levels are elevated in heart failure (HF) animal models and HF patients, but also increase in healthy individuals in response to physical activity. Therefore, CGB seems to integrate information from myocardial stress and systemic neuro-endocrine activation. Substantial gaps remain in our understanding of CGB regulation in HF.Methods and results: We conducted a retrospective registry study including 372 patients. CGB and N-terminal pro-BNP (NT-proBNP) plasma levels were assessed in acute HF and chronic valvular HF patients and controls. CGB levels were significantly increased in acute HF and chronic valvular HF, but significantly higher in the latter. Patients in chronic valvular HF with severe mitral regurgitation (cHF-MR) showed significantly higher CGB levels than patients in chronic valvular HF with severe aortic stenosis. CGB levels progressively increased with worsening NYHA functional status and were moderately correlated to NT-proBNP, but independent of left ventricular (LV) ejection fraction (LVEF), LV mass, age and body weight. Finally, cHF-MR patients showed significant reductions of CGB levels after interventional mitral valve repair.Conclusion: CGB is a promising emerging biomarker in HF patients with unique potential to integrate information from myocardial stress and neuro-endocrine activation.

Prognostic value of soluble ST2 biomarker in heart failure patients with reduced ejection fraction – A multicenter study

ObjectiveTo study the prognostic value of soluble Suppression of Tumorigenicity-2 (sST2) in heart failure patients with reduced ejection fraction (HFrEF). MethodsIn this prospective, observational, multicenter study, patients with heart failure (HF) and left ventricular ejection fraction (LVEF) <50% were included. Clinical evaluation and serum levels of sST2 were estimated at five time points during follow up. Study endpoint was the relationship of baseline and serial sST2 concentration in the blood to the composite endpoints of cardiac death and re-hospitalization for worsening of HF during one year follow up period. ResultsA total of 141 patients were enrolled. The mean age was 60±10.4years. At baseline evaluation, 49.6% patients were in New York Heart Association (NYHA) class III and 36.2% in class IV. Adverse events were observed in 57 patients (40.4%); 25 (17.7%) were re-hospitalized due to worsening of HF and 32 (22.7%) died due to cardiac causes. The median value of baseline sST2 was 46.36ng/ml (IQR 31.30–78.38). sST2 concentration at baseline was significantly higher among patients with adverse events in comparison to patients without adverse events (p=<0.001). Receiver operating characteristic curve (ROC) for baseline sST2 concentration identified 49ng/ml as optimal cut-off value to predict cardiac death and re-hospitalization, with a sensitivity and specificity of 72% and 75%, respectively. ConclusionIn patients with HFrEF, sST2 concentration at baseline as well as on serial testing was significantly correlated with cardiac death and re-hospitalization for worsening of HF.

Renin-Angiotensin-Aldosterone System Parameters as Biomarker in Heart Failure Patients With Preserved Ejection Fraction: Focus on Angiotensinogen.

Renin-Angiotensin-Aldosterone System Parameters as Biomarker in Heart Failure Patients With Preserved Ejection Fraction: Focus on Angiotensinogen.

Short- and Long-term Biologic Variability of Galectin-3 and Other Cardiac Biomarkers in Patients with Stable Heart Failure and Healthy Adults.

Galectin-3 (Gal-3) has been suggested as a prognostic biomarker in heart failure (HF) patients that may better reflect disease progression than traditional markers, including B-type natriuretic peptide (BNP) and cardiac troponins. To fully establish the utility of any biomarker in HF, its biologic variability must be characterized. To assess biologic variability, 59 patients were prospectively recruited, including 23 male and 16 female patients with stable HF and 10 male and 10 female healthy individuals. Gal-3, BNP, and high-sensitivity cardiac troponin I (hs-cTnI) were assayed at 5 time points within a 3-week period to assess short-term biologic variability. Long-term (3-month) biologic variability was assessed with samples collected at enrollment and after 4, 8, and 12 weeks. Among healthy individuals, mean short-term biologic variability, expressed as intraindividual CV (CVI), was 4.5% for Gal-3, 29.0% for BNP, and 14.5% for hs-cTnI; long-term biologic variability was 5.5% for Gal-3, 34.7% for BNP, and 14.7% for hs-cTnI. In stable HF patients, mean short-term biologic variability was 7.1% for Gal-3, 22.5% for BNP, and 8.5% for hs-cTnI, and mean long-term biologic variability was 7.7% for Gal-3, 27.6% for BNP, and 9.6% for hs-cTnI. The finding that Gal-3 has minimal intraindividual biological variability adds to its potential as a useful biomarker in HF patients.

Predictive Value of Biomarkers in Patients with Heart Failure

Heart failure (HF) is a complex syndrome with high morbidity and mortality while, myocardial injury, hemodynamic overload, genetic, neurohormonal, inflammatory and biochemical factors are implicated in the development and progression of the disease. Interestingly, despite the development of several diagnostic tests, HF diagnosis remains clinical, based on symptoms and signs, while there is a poor relationship between symptoms and the prognosis of HF. Several biomarkers have recently been examined for their efficacy to predict outcome and assess prognosis of HF patients. The best studied for its prognostic ability sub-group of biomarkers is the neurohormones including the natriuretic peptides, the components of the renin-angiotensin-aldosterone system and the catecholamines. Others sub-groups of biomarkers include inflammatory and oxidative stress markers, extracellular matrix remodeling markers and myocardial injury markers (such as troponins I and T). Nevertheless, it is difficult to access a single biomarker fulfilling our need to evaluate prognosis and guiding treatment in acute or chronic HF patients, thus the predictive ability of combined biomarkers is recently under research. Therefore, further studies are needed to elucidate the clinical significance of these biomarkers. In the present review, we will discuss the usefulness and significance of potentials or established biomarkers in HF patients focusing on their ability to predict adverse events, morbidity and mortality.