Novel heart failure biomarkers: why do we fail to exploit their potential?

Figures & data

Figure 1. Novel heart failure biomarkers are not cardiac specific. A schematic depiction of the contribution of the heart and other organs and tissues to circulating plasma levels of several protein/peptide heart failure (HF) biomarkers. Only a selection of biomarkers is cardiac specific and many (novel) HF biomarkers are also produced in other organs and tissues. Within the boxes, the names of the biomarkers and associated processes are shown. Abbreviations are explained in the text.

Table 1. Overview of selected (novel) heart failure biomarkers and associated conditions besides heart failure.

Heart failure biomarker group	Biomarkers	Biomarker level also associated with:	References
Biochemical strain	Natriuretic peptides (i.e. BNP, NT-proBNP)	Fluid overload Obesity (lowering of levels) Kidney dysfunction	[18,22–24,26,31,32,192]
Cardiomyocyte injury	hsTn	Myocardial infarction	[37–39]
	H-FABP	Myocardial infarction	[99–103,105,106]
Extracellular matrix turnover and remodeling	Gal-3	Kidney fibrosis Kidney dysfunction COPD Breast cancer Gastric cancer Obesity	[7,43–58]
	sST2	Breast cancer Gastric cancer Diabetic nephropathy Liver failure	[41,42,62–66,68–71]
	HE4	Ovarian cancer Kidney fibrosis Kidney dysfunction Colorectal cancer	[72–82]
Inflammation	IL-6	Infection Post-surgery Stroke	[110,111,115–119,121]
	GDF-15	Pulmonary embolism Pulmonary arterial hypertension Pneumonia Renal disease Sepsis	[126–132]
	PCT	Bacterial infection Pneumonia Systemic inflammation Sepsis Kidney dysfunction Venous congestion	[134,135,137,138]
	ADM	Sepsis Diabetic retinopathy Pneumonia COPD	[139,141–143,193–195]
Metabolism	IGFBP-7	Hepatocellular carcinoma Insulin resistance Metabolic syndrome Kidney injury Endometriosis Diabetic hemodialysis Soft tissue sarcoma COPD	[87,91–98]
Endothelial dysfunction	CD146	Pulmonary edema Peripheral venous congestion Liver cirrhosis Kidney dysfunction Atherosclerosis COPD	[146,148–159]

ADM: adrenomedullin; BNP: brain natriuretic peptide; CD146: cluster of differentiation 146; COPD: chronic obstructive pulmonary disease; Gal-3: galectin-3; GDF-15: growth differentiation factor 15; HE4: human epididymis protein 4; H-FABP: heart fatty acid-binding protein; hsTn: high sensitivity cardiac troponin; IGFBP-7: insulin-like growth factor-binding protein 7; IL-6: interleukin 6; NT-proBNP: N-terminal prohormone of brain natriuretic peptide; PCT: procalcitonin; sST2: soluble suppression of tumorigenicity 2.

Figure 2. Two pillars of HF biomarker research. HF plasma biomarkers are currently predominantly investigated in clinical cohorts. Despite these investigations, progression in the clinical use of HF biomarkers is limited. Systematic improvements in clinical HF biomarker research have therefore been included to generate the required information [186,187]. We now propose an additional pillar of HF biomarker research, namely, the preclinical pillar, to provide additional information from studies in animals that should enhance our understanding, and together should pave the way to finally exploit these novel biomarkers. As in clinical studies, this will require systematic approaches and reports as indicated.

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