Researchers identify potential drug targets for future heart failure therapeutics microbiologystudy

Heart failure remains a substantial burden for patients due to its high prevalence and limited therapeutic options. Heart failure is classified into two major clinical subtypes—heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF).

While there have been significant therapeutic advances in HFrEF, the rate of complications and death from HFrEF remains high. Additionally, most drugs that have shown benefits for patients with HFrEF have not demonstrated a comparable benefit in patients with HFpEF, highlighting a critical need for the development of targeted therapies for both subtypes.

In a study appearing in Nature Cardiovascular Research , researchers analyzed a large genetic dataset and used multi-omics to identify 58 novel drug targets for both HFpEF and HFrEF. The findings have the potential to guide the development of effective drugs for patients with different types of heart failure, say the researchers.

The team used a large-scale multi-omics approach to analyze genetic data from 55,378 patients with HFpEF and HFrEF from the Veterans Affairs (VA) Million Veteran Program (MVP). They leveraged transcriptomics and proteomic data to analyze over 15,000 genes to identify targets with causal relevance to both HFpEF and HFrEF.

For each gene identified as a potential therapeutic target through analyses, the researchers further explored additional biological evidence to strengthen the causal link between protein and heart failure subtype. They then validated the findings in a multi-ancestry genetics dataset of 175,000 individuals of African American, Hispanic and European descent and replicated the results using an alternative proteomics platform.

The team identified 70 genes associated with HFrEF and 10 genes associated with HFpEF. Notably, the drug targets for HFpEF and HFrEF did not overlap, highlighting the importance of developing subtype-specific therapeutic strategies.

Among the genes identified, they found several with strong potential for novel drug discovery. Additionally, the team identified several genes that, when targeted, may be suitable for drug repurposing for both subtypes of heart failure.

The team believes that the findings reveal promising opportunities for both drug development and drug repurposing. They anticipate that the identification of several genes as putative therapeutic targets for HFpEF and HFrEF will be of value in the development of novel therapeutic strategies for these conditions.

Next, the researchers will need to conduct experimental studies using new datasets to further explore the biological mechanisms underlying these targets, particularly those with limited prior biological evidence. These types of studies will be critical to validate the therapeutic potential of the identified targets and advance them toward clinical application.