Prognostication of Heart Failure Evolution: From Circulating Biomarkers to Genetic Risk Predictive Score

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Background

During the last decade, circulating biomarkers were determined as useful and promising tool for heart failure diagnosis, heart failure risk stratification, and prognosis for clinical outcomes directly and indirectly related to heart failure advance. Although numerous circulating biomarkers have been identified and investigated in heart failure patients, their implementation in routine clinical practice has so far remained largely unsuccessful. Current clinical guidelines for heart failure reported by the European Society of Cardiology (ESC) and American Heart Association (AHA) have yielded different recommendations regarding cardiac-specific biomarkers predominantly. For instance, the ESC recommended natriuretic peptides for heart failure, but did not recommended high sensitivity troponins, galectin-3, soluble suppressor of tumorigenicity receptor-2.

These are several concerns whether these biomarkers distinguished from natriuretic peptides could have additional diagnostic value, such as the possibility to use in repeated measurements, and available at a reasonable cost. These uncertainties force exploration and investigation into a wide range of other biomarkers (inflammatory cytokines, copeptine, procalcitonine, adrenomedullin, irisin, human epididymis protein 4, insulin-like growth factor-binding protein, miRNAs). These markers may have the potential to predict cardiac and vascular remodeling as well as mortality among patients with different phenotypes of HF. Understanding the innate molecular mechanisms that are pathogenetically associated with cardiac remodeling and progression of HF may open up new predictive and therapeutic possibilities for HF. This can include biomarker-guided therapy and serial measures of biomarker levels for personified risk stratification.

This Special Issue will discuss the biology of these biomarkers and provide clear explanations in detail whether most of these biomarkers are promising cardiac biological markers or if they reflect typical pathological processes, such as biomechanical stress, fibrosis, cell death, and inflammation. Comparison of diagnostic and clinical effectiveness, clinical and predictive utility, and cost-effectiveness of a wide range of old and brand new biomarkers for monitoring of HF evolution and guided-therapy of HF will also be considered. Moreover, it will report clinical evidence regarding the predictive add-on values of multiple biomarkers’ models in HF and discuss the advantages and disadvantages of these approaches for personalizing monitoring and therapy of HF. Additionally, recent advances and remaining uncertainties regarding the use of the most relevant cardiovascular biomarkers will be disputed and reported in detail. The practical considerations concerning the clinical use of the diagnostic and prognostic biomarkers and potential therapeutic targets in HF will be elucidated here.

Potential topics include but are not limited to the following:
• molecular mechanisms in heart failure development and advances
• inflammation and fibrosis in heart failure
• immunological mechanisms in heart failure development
• cardiac transcriptional remodeling and hypertrophy
• epigenetics and co-morbidities in different etiological subtypes of heart failure
• conception and clinical implementation of biomarker-based risk assessment in heart failure
• DNA methylation and histone modification in heart failure and hypertrophy
• noncoding RNAs in cardiac pathophysiology
• microRNAs signature in cardiac remodeling and heart failure
• endogenous cardiac regeneration via gene expression manipulation
• genetic biomarkers in heart failure
• single nucleotide polymorphism of genes in adverse cardiac remodeling
• pharmacological inhibition of transcriptional machinery
• regenerative strategies in prevention of heart failure
• differences between the ESC and AHA guidelines regarding the currently used and possible future markers
• emerging role of natriuretic peptides in heart failure diagnose and stratification
• inflammatory biomarkers in risk stratification among heart failure patients
• biomarkers with therapeutic potencies
• progenitor cells as a novel biomarker for risk stratification in heart failure
• micro vesicles in heart failure: diagnostic and predictive value
• novel biomarkers for heart failure risk stratification
• biomarker-guided therapy for heart failure
• biomarkers and surrogate endpoints in randomized clinical trials
• promising biomarker-based predictive models in heart failure
• comparison of old (growth differentiation factor-15, vascular endothelial growth factor, factor growth of fibroblast-21, copeptine, procalcitonine, adrenomedullin, oxidative stress biomarkers) and new biomarkers (macrophage inhibitory cytokine-1, irisin, human epididymis protein 4, insulin-like growth factor-binding protein, extracellular vesicles, progenitor cells, stem cells’ secretom, genetic / epigenetic biomarkers including non-steroidal anti-inflammatory drug-activated gene and signature of non-coding RNAs)

Keywords: heart failure, prognostication, circulating biomarkers, genetic biomarkers, guided therapy

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