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Identifying Pathophysiological Mechanisms in Heart Failure With Reduced Versus Preserved Ejection Fraction
Jasper Tromp1, B Daan Westenbrink2, Wouter Ouwerkerk3
1Department of Cardiology, University of Groningen, Groningen, the Netherlands; National Heart Centre Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore.
Journal of the American College of Cardiology
|September 1, 2018
Summary
This study reveals distinct biological pathways for heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). HFrEF pathways involve cellular metabolism, while HFpEF pathways relate to inflammation and extracellular matrix changes.
Area of Science:
- Cardiology
- Biomarker Discovery
- Systems Biology
Background:
- Understanding pathophysiological differences between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) is crucial.
- Existing knowledge lacks specific biological pathway distinctions for HFrEF and HFpEF.
Purpose of the Study:
- To identify and establish unique biological pathways associated with HFrEF and HFpEF.
- To differentiate the molecular underpinnings of various heart failure types.
Main Methods:
- Network analysis of 92 biomarkers in 1,544 heart failure (HF) patients.
- Independent validation in a separate cohort of 804 HF patients.
- Enrichment of protein-protein interaction networks to define biological pathways.
Main Results:
- Identified 8 unique correlations for HFrEF and 6 for HFpEF.
- HFrEF central proteins include NT-proBNP, GDF-15; HFpEF central proteins include integrin beta-2, beta-catenin.
- HFrEF pathways linked to DNA binding and protein metabolism; HFpEF pathways linked to cytokine response and inflammation.
Conclusions:
- Biomarker profiles in HFrEF are associated with cellular proliferation and metabolism.
- Biomarker profiles in HFpEF are associated with inflammation and extracellular matrix reorganization.
- Distinct biological pathways underscore the heterogeneity of heart failure phenotypes.
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