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

Nazha Hamdani1,2,3,4, Sarah Costantino5, Andreas Mügge2,3

  • 1Institute of Physiology, Ruhr University, Bochum, Germany.

European Heart Journal
|May 5, 2021
PubMed

Insights

Heart failure with preserved ejection fraction (HFpEF) is a major unmet need. Epigenetic modifications offer novel, reversible biomarkers and therapeutic targets for personalized HFpEF management.

Area of Science:

  • Cardiovascular Medicine
  • Molecular Biology
  • Genetics

Background:

  • Heart failure with preserved ejection fraction (HFpEF) is a prevalent, untreatable cardiovascular disease, disproportionately affecting women and incurring high healthcare costs.
  • The diverse phenotypes of HFpEF complicate diagnosis and treatment, highlighting the urgent need for novel therapeutic strategies.
  • Epigenetic modifications, influenced by environmental factors, play a crucial role in the molecular pathways leading to HFpEF, including oxidative stress, inflammation, and cardiac remodeling.

Purpose of the Study:

  • To explore the significance of clinical epigenetics in addressing the unmet need in heart failure with preserved ejection fraction (HFpEF).
  • To highlight epigenetic modifications as potential diagnostic biomarkers and therapeutic targets for personalized HFpEF management.
  • To review the role of epigenetics in environmental modulation of gene expression relevant to HFpEF pathogenesis.

Main Methods:

  • Review of current literature on epigenetic mechanisms in HFpEF.
  • Analysis of advances in high-throughput sequencing, computational epigenetics, and machine learning for biomarker discovery.
  • Examination of existing and emerging epigenetic drugs ('epidrugs') targeting chromatin and non-coding RNAs.

Main Results:

  • Epigenetic biomarkers reflect environmental and lifestyle influences and are reversible, offering dynamic monitoring capabilities.
  • Epigenetic modifications are implicated in key pathological processes of HFpEF, such as left ventricular remodeling.
  • Several FDA-approved 'epidrugs' demonstrate potential in preventing transcriptional alterations associated with HFpEF.

Conclusions:

  • Clinical epigenetics presents a promising frontier for the personalized management of HFpEF.
  • Epigenetic information holds significant potential for both diagnostic and therapeutic applications in HFpEF patients.
  • The reversible nature of epigenetic changes offers a unique opportunity for monitoring disease progression and treatment response in HFpEF.

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

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