Comparing de novo heart failure and acute decompensated heart failure using a proteomic approach

Abstract Background Acute heart failure (HF) is defined as new or worsening symptoms of HF and stands as the most common cause of unscheduled hospital admission in patients above the age of 65. Acute HF can be classified into de novo HF (DNHF), defined as no previous history of HF, and acutely decompensated HF (ADHF), defined as worsening symptoms of HF in individuals with a prior diagnosis of HF. Clinically, it is relevant to distinguish ADHF from DNHF as they differ regarding aetiology, comorbidities, mortality, and morbidity. The aim of this study was to compare DNHF and ADHF using a proteomic approach. Method Using a proximity extension assay in a Swedish HF cohort, a total of 324 individuals hospitalized for acute HF underwent proteomic analysis of 92 proteins. The population was categorized into DNHF and ADHF, subsequently comparing normally distributed proteins using an independent samples t-test. Non-normally distributed proteins were compared using the Mann-Whitey U-test. To adjust for multiple testing, Benjamini Hochberg method was applied with a false discovery rate of 5%. Fold change was calculated by subtracting the mean or median protein concentration in ADHF from DNHF. As protein concentrations are expressed on a log2-scale, the difference between the groups equals the fold change. Proteins were considered differentially expressed at a fold change threshold of 1.15. The proteins that met a cut-off, were thereafter analysed with a pathway enrichment analysis using Reactome (only a corrected p-value ≤0.05 was considered significant). Results Complete data was available for n=317 (30.3% women; mean age 74.6) individuals (Table 1). After FDR adjustment, differential protein expression analysis yielded 56 differentially expressed proteins. After applying the fold change threshold, 51 proteins were significantly up regulated in ADHF compared to DNHF and one (Paraoxonase 3) was significantly downregulated. The most prominently up-regulated protein was fatty acid binding protein-4 (FABP4) (fold change 1.68, p <0.001). The largest number of proteins were related to neutrophil degranulation (Figure 1). Conclusion In patients hospitalized for acute HF, we identified several common pathways of the proteins differentially expressed in DNHF compared with ADHF. Neutrophil degranulation was related to the largest number of proteins. The most prominently up regulated protein was FABP4. These findings may inspire future investigation into the different underlying molecular mechanisms in ADHF and DNHF and reveal potentially different targets of treatment between the two conditions.Figure 1.Pathway enrichment analysis