Health
New research identifies potential drug targets for heart failure
How would you summarize your research for a lay audience?
Heart failure remains a major burden for patients due to its high prevalence and limited treatment options. Heart failure is classified as two major clinical subtypes with conserved elimination rates – heart failure and heart failure with reduced elimination rates (HFREF). Although there have been significant therapeutic advances in HFREF, complications and mortality from HFREF remain high. Furthermore, most drugs that have shown benefits for HFREF patients do not show comparable benefits for HFPEF patients. It highlights the important need for the development of targeted therapies for both subtypes.
Our new study analyzed a large genetic dataset and used multiomics to identify 58 novel drug targets, both HFPEF and HFREF. Our findings may lead to the development of effective drugs in patients with different types of heart failure.
What methods and approach did you use?
Using a large-scale multiomics approach, genetic data from 55,378 patients in the Veterans' Program (MVP) of Veterans' Issues (VA) were analyzed. Using transcriptomic and proteomic data, we analyzed over 15,000 genes to identify causal targets for both HFPEF and HFREF.
Additional biological evidence was further explored to enhance the causal relationship between proteins and heart failure subtypes for each gene identified as a potential therapeutic target through analysis. We then validated our findings on a multi-ancestry genetics dataset of 175,000 people from African American, Hispanic and European incent, and replicated the results using an alternative proteomics platform.
What did you find?
From the assessment, we identified 70 genes associated with HFREF and 10 genes associated with HFPEF. In particular, the drug targets of HFPEF and HFREF do not overlap, highlighting the importance of developing subtype-specific therapeutic strategies.
Among the identified genes, we discovered several that have strong potential for new drug discovery. Furthermore, we identified several genes that may be suitable for drug reuse for both subtypes of heart failure when targeted.
What makes sense?
Our findings reveal promising opportunities for both drug development and drug reuse. We expect the identification of several genes as putative therapeutic targets for HFPEF and HFREF to be valuable in the development of new therapeutic strategies for these conditions.
What is the next step?
Experimental studies should be conducted using new datasets to further explore the biological mechanisms underlying these targets, particularly those with limited prior biological evidence. . These types of studies are important to validate the therapeutic potential of identified targets and to advance them towards clinical applications.
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Journal Reference:
Rasooly, D. , et al. (2025). Large multiomics identify drug targets for heart failure with reduced ejection fraction. Natural Cardiovascular Research. doi.org/10.1038/S44161-025-00609-1.
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