Single-cell transcriptomic profiling reveals cell type heterogeneity between HFpEF and HFrEF.

Heart failure with preserved ejection fraction (HFpEF) as a high heterogeneity clinical syndrome, is commonly associated with diastolic dysfunction, and has no effective therapy, which is obviously distinct from Heart failure with reduced ejection fraction (HFrEF). Currently the differences of cell type heterogeneity between HFpEF and HFrEF remain largely unknown. Here we illustrate an atlas consisting of 21,747 cardiac cells, including both HFpEF and HFrEF. Cell-cell communication analysis reveals cardiomyocytes rather than endothelium or fibroblasts were dominant communication "hub" in HFpEF. The subtypes of cardiomyocytes are highly heterogeneous between HFpEF and HFrEF. Notably, a specific subtype of cardiomyocytes shows significant gene expression associated with the metabolism of fatty acids. Additionally, regulon analysis reveals that Ppargc1a, Atf6, E2f6, and Mitf exhibited specific elevated regulation in the subtype of cardiomyocytes of HFpEF. Furthermore, we have identified 210 HF susceptibility genes from HF-associated GWAS data. After integrating scRNA-seq, GWAS, and eQTL data, the genetic susceptibility underlying HFpEF and HFrEF were discussed. In conclusion, this study not only comprehensively characterizes the differences of cardiomyocytes changes but also provides insights into potential targets for cell type- and subtype-specific molecules between HFpEF and HFrEF.