Heart failure remains a leading cause of premature death in patients with established cardiovascular (CV) disease [1]. Prevalence of HF has been exhibiting a strong tendency to growth worldwide. Although there are several clinical guidelines regarding diagnosis, prevention and treatment of HF, prediction of HF development in various patient populations is still under scientific discussion. Biological markers have become a powerful tool for stratification ofHF patients at risk and biomarker-guided therapy [2].Updated clinical recommendations have been reported that the natriuretic peptides, galectin-3,high-sensitivity troponin and soluble ST2 protein are commonly used biomarkers, which remain a central part of routine clinical practice to stratify patients at risk of HF development, arisk of primary admission / readmission to the hospital, and CV death. Confusingly, the role of biomarkers in modification of treatment care considerably relates to aging, CV disease and metabolic co-morbidities, kidney clearance, and higher individual biological variability of biomarkers, which negatively effects on interpretation of circulating biomarkers’ level[3].In this context, novel biomarkers are required to assist in the titration of medical therapy and improve prediction of widely used scores [4].

Procalcitonin, copeptin, heart-type fatty acid-binding protein (hFABP) and growth differentiation factor 15 (GDF-15) has been suggested to be novel biomarkers in HF.

Procalcitoninis known a precursor of the calcitonin, which is produced and actively secreted by the parafollicular C cells of the thyroid gland and involved in regulation of calcium homeostasis [5]. Recent clinical studies have shown that procalcitonin as an inflammatory biomarker had a pretty accurate diagnostic ability to sepsis, shock, bacterial complications of some diseases [6-8]. Additionally, this biomarker may help to manage the patients with HF when antibiotic use is needed or the critical state has been verified [4]. However, there is not strong evidence regarding procalcitotin use in biomarker-guided therapy to adjust dosage of drugs for HF individuals.

Copeptin is C-terminal peptide derived from the precursor molecule of arginine vasopressin, which plays a pivotal role in fluid retention and electrolyte homeostasis [9]. In the general population elevated level of copeptin strongly associated with increased CV mortality [10]. Additionally, based on results of serial measurements of copeptin level it has been suggested that the increased copept in concentration or trend to elevation of one area independent risk factor for long-term HF-related clinical outcomes and sudden death in patients with established CV disease [11-13].Being able to better predict all-cause mortality rate and HF-related risks including death and admission to the hospital copeptin might be considered as much more accurate biomarker than natriuretic peptides for optimize medical care in HF patients [14, 15]. Unfortunately, there are large body of evidence regarding that the level of copeptin might relate closely to some metabolic abnormalities including hyperglycemia that sufficiently limits the predictive power of the biomarker in serial measurements especially in patients with diabetes and obesity [14, 16]. However, the improvement of diagnostic reliability of copeptin may achieve by means use of combined biomarker strategy, in particular it might be based on copeptin and natriuretic peptides (N-terminal pro-brain natriuretic peptide, mid-regional pro-atrial natriuretic peptide) [17, 18]. Finally, circulating level of copeptinare now recognized a promising biomarker with better discriminative value for both all-cause mortality and HF-related outcomes general population and individuals with established CV disease.

The main biological role of heart type of FABP (hFABP) is to facilitate the long-chain fatty acids re-uptake, attenuate calcium transport in cardiomyocytes and regulate inflammatory response in reply to some lipid signals [19]. hFABP is predominantly expressed in cardiomyocytes and is powerful biomarker of myocardial injury. Recent studies have shown that the hFABP has better predicted CV outcomes to other biomarkers of cardiac damage, i.e. myoglobin and high-sensitive troponins [3, 14, 20], whereas elevated intestinal FABP would identify patients with advanced HF who had severe fluid retention and intestinal congestion [21]. Overall, the H-FABP may better provide prognostic information on survival and more precise reflecta risk of major CV events during hospitalization period and short-time after discharge than natriuretic peptides, cardiac troponins and galectin-3. However, the role of several types of FABP in HF is not fully clear. Large clinical studies are required to more accurately explain the predictive value of these biomarkers.

Growth differentiation factor (GDF)-15 belongs to the super family of transforming growth factor-β [22]. GDF-15 is widely expressed on the surfaces of various cells. In HF GDF-15 is secreted by injured cardiomyocytesin response to ischemia, reperfusion, inflammatory cytokine stimulation and exposure to biomechanical stress [14]. Elevated level of circulating GDF-15 was found in HF individuals irrespectively etiology of cardiac dysfunction [23]. There is strong evidence regarding being tight interrelationship between circulating level of GDF-15 and HF signs and symptoms, reduced left ventricular ejection fraction [24]. Although serial biomarker evaluation has not showed superiority of incremental predictive ability in GDF-15 versus natriuretic peptides in acute HF [25], in chronic HF multiple marker strategy based on GDF-15, galectin-3 and natriuretic peptides might exhibit several advantages before conventional approach in ability to predict all-cause mortality, CV mortality and HF-related outcomes in outpatients with HF [26, 27]. Finally, there are several controversies regarding importance of predictive value for survival and incremental prognostication in diagnosis of HF. There is need in larger clinical studies with higher statistical power and head-to-head comparison of biomarkers to clear their role in diagnosis and guided therapy of HF.

Conclusions: Although recent clinical trials have been exhibited much more information regarding biomarker use in prognostication of HF, there is considerable limitation in head-to-head comparison of several biomarkers and biomarker-based strategy to treat of HF. All these are a cause of some speculations around advantages and shortcomings of biomarker-based management of HF including new biological indicators, such as procalcitonin, copeptin, hFABP and GDF-15. Novel biomarkers are needed to be investigated in details, while there is suggestion that multiple biomarker models would be better in prediction HF evolution and outcomes than even single brand new biomarker.