Epigenetic drugs: a new frontier in the treatment of heart failure

Uncovering the secrets of genome flexibility not only contributed to the development of research in this area, but also served as an impetus for the development of new treatments for human diseases. A better understanding of the biology of chromatin (DNA/histone complexes) and non-coding RNAs (ncRNAs) has enabled the development of epigenetic (epi) preparations capable of modulating transcriptional programs associated with cardiovascular disease. This is especially true in heart failure, where epigenetic mechanisms have been shown to underlie the development of several pathological processes such as left ventricular hypertrophy, fibrosis, cardiomyocyte apoptosis, and microvascular dysfunction. Targeting epigenetic signals may represent a promising approach, especially in patients with heart failure with preserved ejection fraction (HFpEF), where the prognosis remains poor and effective treatments are not yet available. Under these conditions, epigenetics can be used to develop individualized therapeutic approaches, paving the way for personalized medicine. Although the beneficial effects of epi-drugs are gaining more attention, the number of epigenetic compounds used in clinical practice remains low, suggesting the need to develop more selective epi-drugs. In this review, we present a list of new promising epi-drugs for the treatment of cardiovascular diseases, with a focus mainly on HFpEF. The therapeutic effect of these drugs is due to the impact on at least one of the three main epigenetic mechanisms: DNA methylation, histone modification, and non-coding RNA.