Key result
Post-acute HF recovery alters circulating proteins at 6 months, led by ~39% lower NT-proBNP.
Why the study?
Most proteomic studies in heart failure are cross-sectional and do not capture temporal changes, leaving longitudinal changes in the circulating proteome from the acute phase of heart failure to recovery poorly defined.
Cohort (n=136)
Recovery from acute heart failure hospitalization over 6 months is characterized by selective rather than global remodeling of the circulating proteome, with notable shifts in NT-proBNP and EpCAM while 83 of 92 measured proteins remained stable.
Answers are grounded in this paper and cite their sources.
Selective proteome remodeling after acute HF hospitalization supports targeted biomarker panels; leaves open predictive value and clinical adoption.
Background Acute heart failure (HF) triggers biological disturbances, reflected in circulating protein levels. While proteomic studies have improved understanding of HF pathophysiology, most are cross-sectional and do not capture temporal changes. How the circulating proteome changes from acute phase to recovery remains poorly defined. We aimed to characterize longitudinal proteomic changes between hospitalization for acute HF and 6-month follow-up. Methods Using a proximity extension assay in a Swedish HF cohort, a total of 136 individuals underwent proteomic analysis of 92 proteins at baseline (hospitalized for acute HF) and 6 months later. Differential protein expression between follow-up and baseline was assessed using the Linear Models for Microarray Data analysis (Limma). Multiple testing was addressed using the Benjamini-Hochberg false discovery rate (FDR). Proteins were considered significantly changed at FDR <0.05, with an additional effect size threshold of |log2FC| ≥0.2 (~15% change) to highlight biologically meaningful changes. Results One-hundred-thirty-six individuals (29 % women; mean age 74.2 ±10.9) had complete baseline and follow-up data. After FDR adjustment, the differential protein expression in follow-up phase vs acute phase yielded 20 proteins. After applying the |log2FC| ≥0.2 threshold 4 proteins were upregulated (higher in the follow-up phase) while 5 proteins were downregulated (lower in the follow-up phase) (figure 1). The most upregulated protein was Epithelial Cell Adhesion Molecule (EpCAM) (log2FC 0.38, ~30% higher, FDR <0.001) while NT-proBNP (log2FC –0.48, ~ 39% lower, FDR 0.003) showed the greatest decrease 6 months later. Most proteins (83/92) remained unchanged (FDR≥0.05 and |log2FC| <0.2) over 6 months (figure 2). Conclusion In this longitudinal proteomic study of patients hospitalized for acute HF, only a small subset of circulating proteins changed meaningfully between the acute phase and 6-month follow-up, while most proteins remained stable. These findings suggest that recovery from acute HF is characterized by selective, rather than global, remodelling of the circulating proteome. Proteins with the largest temporal shifts—most notably NT-proBNP and EpCAM—may reflect biological processes linked to acute decompensation and recovery and warrant further mechanistic and prognostic investigation.BarplotVolcanoplot
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Dieden et al. (2026) conducted a cohort in Acute heart failure (n=136). 6-month recovery phase post-hospitalization for acute heart failure vs. Baseline acute heart failure hospitalization phase was evaluated on Differential expression of 92 circulating proteins (FDR <0.05 and |log2FC| ≥0.2). Recovery at 6 months post-acute HF hospitalization altered 9 of 92 proteins (|log2FC| ≥0.2, FDR <0.05), led by EpCAM (+30%, FDR <0.001) and NT-proBNP (-39%, FDR=0.003).
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