Table 3.

Advantages and disadvantages of plausible biomarkers without proven value in current HF management

Biomarker	Correspondence to basic pathophysiological mechanism/triggers	Advantages	Disadvantages
Pro- or telopeptides of collagen type-I	ECM remodeling	Independent predictor of high risk of HF, HF outcomes, and death. Additive prognostic value when compared with the concentrations of NT-proBNP. Available for a multi-marker approach for risk stratification.	Unavailable for serial measures. Low diagnostic value
Bone-related proteins	ECM remodeling	Independent of NPs’ predictive value for CV mortality, HF hospitalization, and arrhythmia. Available for a multi-marker approach for risk stratification.	Unavailable for serial measures. Low diagnostic value
GDF15	Inflammation	Predicts ischemia-induced HF and AF. Available for a multi-marker approach for risk stratification. Available for biomarker-guided therapy	Not available for prediction of newly diagnosed HF and non-ischemic cardiomyopathy.
Renal dysfunction biomarkers	Renal injury	Available for serial monitoring. Association of HF-related outcomes	No relation to change of HF management.
Biomarkers of neurohumoral activation	Neurohumoral activation	Available for mortality prediction regardless of HF phenotypes.	Strict similarity in predictive abilities with those of NPs. Available for acute HF rather than chronic HF.
Oxidative stress biomarkers	Mitochondrial injury	Relatively low-cost measures.	Low accuracy, predictive ability, reproducibility, and reliability.
Skeletal muscles dysfunction biomarkers	Muscles injury	Available for mortality prediction regardless of HF phenotypes. Association of HF-related outcomes. Available for biomarker-guided therapy.	No validated scores to use.

Abbreviations: AF, atrial fibrillation; ECM, extracellular matrix; CV, cardiovascular; HF, heart failure; GDF-15, growth differentiation factor-15; NPs, natriuretic peptides.