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With more than 25 million people affected, heart failure (HF) is a global threat. As energy
production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic
changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and
mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular
heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients
with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified
several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM
(p = 1.7 × 10−6
). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting
enzymes of these pathways could also be found and validated in our second stage of metabolite
assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a
new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades
that potentially represent suitable intervention targets.