The role of serial cardiac biomarkers in prognostication and risk prediction of chronic heart failure: additional scientific insights with hemodynamic feedback

Figures & data

Figure 1. Main pathological pathways involved in heart failure and a selection of associated biomarkers. NT-proBNP, N-terminal pro hormone BNP. BNP, Brain natriuretic peptide. MR-proANP, Mid-regional pro atrial natriuretic peptide. MR-proADM, Mid-regional proadrenomedullin. (hs)-TnT/TnI, (high sensitivity) – troponin T/I. MPO, myeloperoxidase. sST2, soluble suppression of tumorigenesis 2. GDF-15, Growth-differentiation factor 15. MMP, Matrix metalloproteinase. (hs)CRP, (high sensitivity) C-reactive protein. CA-125, Cancer antigen 125. NGAL, Neutrophil gelatinase-associated lipocalin. Parts of the figure were drawn by using pictures from Servier Medical Art licensed under a Creative Commons Attribution 3.0 unported license.

Table 1. Neurohormonal activity pathway.

	Circulating biomarkers in the neurohormonal activity pathway	Mechanism of action	Potential value in HF disease
3.1.1 Natriuretic peptides	NT-proBNP	Natriuresis, vasodilation, diuresis and inhibition of sympathetic nervous system including RAAS.	Elevated levels of NT-proBNP predict worse outcomes in CHF patients [22–26].
	BNP		BNP acts as a predictor of HF related events (e.g. mortality & hospitalization) [25,32,33].
	MR-proANP		Elevated levels of MR-proANP are associated with poor survival in CHF patients [34–36].
3.1.2 Adrenomedullin	MR-proADM	Natriuresis, vasodilatory and hypotensive effects on the systemic and pulmonary circulation.	MR-proADM demonstrated a significant positive predictive value for HF prognostication [37–39].

Table 2. Myocardial necrosis and remodeling pathways.

	Circulating biomarkers in the Myocardial necrosis pathway	Mechanism of action	Potential value in HF disease
3.2.1 high-sensitivity cardiac troponins	hs-cTnT	Myocardial contractile function	hs-cTnT and hs-cTnI have a cardio-specific diagnostic and prognostic utility in CHF [9,43–47].
	hs-cTnI
	Circulating biomarkers in the Myocardial remodeling pathway
3.3.1	sST2	Myocardial fibrosis, cardio myocyte hypertrophy and apoptosis	Elevated levels of sST2 are associated with increased risk of all-cause mortality and HF-hospitalization [10,51,52].
3.3.2	GDF-15	Regulates cardiac function and body growth	GDF-15 elevated levels are linked to HF mortality and hospitalization [11,55,56].
3.3.3	Galectin-3	Signaling pathways, cell growth and differentiation, cell-cell and cell-ECM adhesion, apoptosis and angiogenesis	Potential biomarker in the prognostication of HF [12,58–61].

Table 3. Renal dysfunction pathway.

	Circulating biomarkers in the renal dysfunction pathway	Mechanism of action	Potential value in HF disease
3.4.1	CysC	Inhibition of cysteine proteases	CysC is an independent predictor of adverse outcomes in CHF [66,67].
3.4.2	NEP	Degradation of natriuretic peptides	Potential prognostic, predictive value [69,70].
3.4.3	NGAL	Bacteriostatic properties, cell survival, inflammation and matrix degradation.	Reliable predictive predictor of prognosis in CHF patients [71–73].

Table 4. Inflammation, oxidative stress, and ECM pathways.

	Circulating biomarkers in the inflammation pathway	Mechanism of action	Potential value in HF disease
3.5.1	CA-125	Inflammatory and congestion marker in HF	Potential as a marker for congestion, prognosis and risk stratification of HF disease [77–79].
3.5.2	(hs)CRP	Inflammatory marker	Elevated (hs)CRP levels are associated with mortality and morbidity in HF [80,81].
3.5.3	IL-6		Elevated levels of expression rises as CHF severity increases [85,87–89].
	Circulating biomarkers in the oxidative stress and ECM pathway
3.6.1	MPO	Innate immune response, endothelial dysfunction	Potential in risk-stratification of CHF patient [97–99,101].
3.6.2	MMPs	Mediation of ECM remodeling and tissue remodeling in inflammation and injury	Predictive strength in clinical outcome predication in HF patients [104,105,109]

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