Leveraging clinical epigenetics in heart failure with preserved ejection fraction: A call for individualized therapies

Nazha Hamdani, Sarah Costantino, Andreas Mügge, Djamel Lebeche, Carsten Tschöpe, Thomas Thum, Francesco Paneni

Research output: Contribution to journalReview articlepeer-review

31 Scopus citations

Abstract

Described as the 'single largest unmet need in cardiovascular medicine', heart failure with preserved ejection fraction (HFpEF) remains an untreatable disease currently representing 65% of new heart failure diagnoses. HFpEF is more frequent among women and associates with a poor prognosis and unsustainable healthcare costs. Moreover, the variability in HFpEF phenotypes amplifies complexity and difficulties in the approach. In this perspective, unveiling novel molecular targets is imperative. Epigenetic modifications - defined as changes of DNA, histones, and non-coding RNAs (ncRNAs) - represent a molecular framework through which the environment modulates gene expression. Epigenetic signals acquired over the lifetime lead to chromatin remodelling and affect transcriptional programmes underlying oxidative stress, inflammation, dysmetabolism, and maladaptive left ventricular remodelling, all conditions predisposing to HFpEF. The strong involvement of epigenetic signalling in this setting makes the epigenetic information relevant for diagnostic and therapeutic purposes in patients with HFpEF. The recent advances in high-throughput sequencing, computational epigenetics, and machine learning have enabled the identification of reliable epigenetic biomarkers in cardiovascular patients. Contrary to genetic tools, epigenetic biomarkers mirror the contribution of environmental cues and lifestyle changes and their reversible nature offers a promising opportunity to monitor disease states. The growing understanding of chromatin and ncRNAs biology has led to the development of several Food and Drug Administration approved 'epidrugs' (chromatin modifiers, mimics, anti-miRs) able to prevent transcriptional alterations underpinning left ventricular remodelling and HFpEF. In the present review, we discuss the importance of clinical epigenetics as a new tool to be employed for a personalized management of HFpEF.

Original languageEnglish
Pages (from-to)1940-1958
Number of pages19
JournalEuropean Heart Journal
Volume42
Issue number20
DOIs
StatePublished - 21 May 2021

Keywords

  • Chromatin changes
  • Epigenetics
  • Heart failure
  • Non-coding RNAs
  • Precision medicine

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