Table 1.

Predictive value of “classic” biomarkers in heart failure.

Heart Failure	Biomarker	Underlying Condition	Pacemaker/ICD	Arrhythmias	Outcome	Number of Patients	Study Design	FU-Duration	Specific Endpoint	Effect on SCD
Biasucci et al., 2006 [27]	CRP	ICM	ICD	VT/VF	CRP is associated with VT/VF	65	Prospective, single center	-	Appropriate ICD shocks for sVT/VF	SCD not directly investigated
Theuns et al., 2012 [33]	hsCRP, BNP	CHF	ICD	VA	Independently associated with ICD appropriate therapy	100	Prospective, single center	24 months	Appropriate ICD therapy, VA	Independent predictor of SCD *
Blangy et al., 2007 [34]	hsCRP, BNP	ICM	ICD	VT	hsCRP and BNP associated with VTs	121	Prospective, single center	1 year	VTs	SCD not directly investigated
Streitner et al., 2009 [35]	hsCRP, IL-6, NT-proBNP	DCM, CAD	ICD	VT/VF	Correlation with occurrence of electrical storm	86	Prospective, single center	9 months	VT/VF or electrical storm	SCD not directly investigated
Biasucci et al., 2012 [36]	hsCRP	ICM	ICD/CRT-D	VT/VF	Not associated with SCD or VT/VF	268	Prospective, multicenter (CAMI-GUIDE study)	2 years	VT/VF or SCD	No effect
Kontantino et al., 2007 [37]	IL-6, TNFα, hsCRP, BNP	CHF	ICD	VT/VF	No correlation with VT/VF	50	Prospective, single center	152±44 days	VT/VF	SCD not directly investigated
Streitner et al., 2007 [41]	IL-6	ICM	ICD	VT/VF	Associated with VT/VF	47	Prospective, single center	9 months	VT/VF	SCD not directly investigated
Cheng et al., 2014 [42]	IL-6, CRP, TNFα-receptor II, pro-BNP	CHF	ICD	VA	IL-6 predictive for appropriate ICD shocks	1189	Prospective, multicenter (PROSe-ICD study)	4 years	Appropriate ICD shock	IL-6 independent predictor of SCD *
Berger et al., 2002 [51]	BNP	CHF	None	SCD	Independent predictor of SCD	452	Prospective, single center	3 years	SCD	Independent predictor of SCD
Watanabe et al., 2006 [52]	BNP	CHF	None	SCD	Associated with SCD when combined with echo parameters, nsVTs and diabetes	680	Prospective, multicenter (CHART study)	-	SCD	Factor associated with SCD
Medina et al., 2016 [53]	BNP	CHF	ICD/CRT-D	VT/VF	Independent predictor of VT/VF	1197	Sub-study, prospective, multicenter (MADIT-CRT study)	1 year	VT/VF	SCD not directly investigated
Christ et al., 2007 [54]	BNP	CHF	ICD	VT/VF	Predictive of VT/VF	123	Prospective, single center	25 months	VT/VF	SCD not directly investigated
Verma et al., 2006 [56]	BNP, CRP	CHF	ICD	Appropriate ICD therapy	BNP predictive of appropriate ICD shocks	345	Prospective cohort single center	13 months	Appropriate ICD shocks	Independent predictor of SCD *
Vrotovec et al., 2013 [57]	BNP	CHF	None	SCD	Not predictive of SCD	512	Prospective single center	1 year	SCD	No effect
Bayes-Genis et al., 2007 [60]	NT-proBNP	CHF	None	SCD	Predictive of SCD	494	Prospective, multicenter (MUSIC study)	36 months	SCD	Independent predictor of SCD
Simon et al., 2008 [62]	NT-proBNP	DCM	None	nsVTs	Correlation with occurrence of nsVTs	30	Prospective, single center	21.6 ± 1.2 months	nsVTs	SCD not directly investigated
Scott et al., 2011 [63]	NT-proBNP, sST2, CRP, IL-6	CHF	ICD	Appropriate ICD therapy	NT-proBNP predictive of appropriate ICD therapy	156	Prospective, single center	15 ± 3 months	Appropriate ICD therapy	Factor associated with SCD *
Klingenberg et al., 2006 [64]	NT-proBNP	ICM	ICD	VA	Independent predictor of ICD therapy	50	Prospective, single center	1 year	Appropriate ICD therapy	Independent predictor for SCD *
Manios et al., 2005 [65]	NT-proBNP	ICM	ICD	VA	Predictive of VA	35	Prospective, single center	1 year	VA	SCD not directly investigated
Yu et al., 2007 [66]	NT-proBNP	ICM	ICD	VT/VF	Predictive of VT/VF	99	Prospective, single center	18 months	VT/VF	SCD not directly investigated
Levine et al., 2014 [67]	NT-proBNP, BNP	CHF	ICD	VA	Independently predictive of appropriate ICD therapy	695	Retrospective, multicenter	-	Appropriate ICD therapy	Independent predictor of SCD *

BNP, B-type natriuretic peptide; CAD, coronary artery disease; CHF, chronic heart failure; CMP, cardiomyopathy; CRP, C-reactive protein; CRT-D, cardiac resynchronization therapy – defibrillator; DCM, dilated cardiomyopathy; hsCRP, high sensitive C-reactive protein; ICD, implantable cardiac defibrillator; ICM, ischemic heart disease; IL-6, interleukin 6; nsVT, non sustained ventricular tachycardia; NT-proBNP, N-terminal pro-B-type natriuretic peptide; SCD, sudden cardiac death; sST2, soluble tool-like receptor-2; sVT, sustained ventricular tachycardia; TNFα, tumor necrosis factor alpha; VA, ventricular arrhythmias; VF, ventricular fibrillation; VT, ventricular tachycardia; sVT, sustained ventricular tachycardia; *If patient had ICD, appropriate therapy was defined as sudden cardiac death.