© 2016 Background/objectives To evaluate whether biomarkers reflecting pathophysiological pathways and selected single nucleotide polymorphisms differ between patients (pts) with heart failure (HF). Methods 110 pts with were involved, including HF pts with preserved ejection fraction (HFpEF, n = 51) with hypertensive origin, HF pts with reduced ejection fraction (HFrEF) with ischemic aetiology (ICM) (n = 32) and HFrEF with dilated cardiomyopathy (DCM) (n = 27). We assessed selected HF biomarkers, echocardiographic examinations and functional polymorphisms selected from six candidate genes: CYP27B1, NOS3, IL-6, TGF beta, TNF alpha, and PPAR gamma. Results Higher concentrations of TNF alpha were observed in pts with hypertensive HFpEF compared to pts with DCM (p = 0.008). Pts with HFpEF had higher concentrations of TGF beta 1 compared to DCM and ICM (p = 0.0001 and p = 0.0003, respectively). For the NOS3 − 786 C/T rs2070744 polymorphism in DCM there were significantly more CT heterozygotes than in ICM and HFpEF. In multivariate analysis TGF beta 1 (p = 0.001) and syndecan 4 (p = 0.001) were the only factors distinguishing HFrEF pts with DCM vs HFpEF and also TGF beta 1 (p = 0.001) and syndecan 4 (p = 0.023) were the only factors distinguishing HFrEF pts with ICM vs HFpEF pts. Conclusions Inflammation mediated through TNF alpha and TGF beta 1 may represent an important component of an inflammatory response that partially drives the pathophysiology of HFpEF. NOS3 − 786 C/T rs2070744 polymorphism in DCM may serve as a marker for more rapid progression of heart failure. The only biomarkers independently distinguishing HFpEF and HFrEF are syndecan 4 and TGF beta 1.