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July 26, 2026BMC MedicineOpen Access

Plasma AHNAK discriminates AF in HF patients with ~0.90 AUC, while deficiency promotes atrial fibrosis.

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Population

59 age- and sex-matched patients hospitalized with acute decompensated HF; primary mouse atrial fibroblasts…

Design

Case-control

Key result

Plasma AHNAK levels strongly discriminated atrial fibrillation in patients with heart failure (AUC = 0.897; 95% CI 0.82-0.97), and AHNAK deficiency promoted atrial fibrotic remodeling.

Authors

WZWengen ZhuZGZhenbang GuYHYuwen Huang

Discussion

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Overview

AHNAK may aid AF discrimination in HF if validated; leaves open clinical adoption pending larger prospective cohorts.

Key Points

  • This research aims to identify molecular determinants that discriminate atrial fibrillation in heart failure patients using integrated proteomics and machine learning.
  • Analyzed samples from 59 patients with acute decompensated heart failure using label-free quantitative plasma proteomics.
  • Performed functional and pathway enrichment analyses on differentially expressed proteins and prioritized biomarkers with machine learning.
  • Conducted in vitro and in vivo experiments to examine the role of AHNAK using TGF-β1-stimulated fibroblasts and a pressure overload model in mice.
  • Identified 126 dysregulated proteins in heart failure patients with atrial fibrillation, with AHNAK being the most upregulated.
  • Machine learning ranked AHNAK as the most discriminative protein for AF discrimination in HF patients (AUC = 0.897, 95% CI: 0.82–0.97).
  • Mendelian randomization analysis indicated a significant protective effect of higher AHNAK expression against atrial fibrillation.

Study Design

Type

Cross-Sectional (n=59)

Structured PICO

P
Population
59 age- and sex-matched patients hospitalized with acute decompensated heart failure, comparing those with atrial fibrillation to those in sinus rhythm.
C
Comparator
HF patients in sinus rhythm (for the human cohort)
O
Outcome
Discriminative plasma biomarkers for atrial fibrillation in heart failure patientssurrogate

Main Result

Effect estimate: AUC 0.897 (95% CI 0.82-0.97)

AHNAK is a promising plasma biomarker for identifying atrial fibrillation in heart failure patients, and its deficiency may mechanistically contribute to atrial fibrotic remodeling.

Limitations

  • Requires external validation in larger and prospective HF cohorts to confirm clinical utility
  • External validation in larger and prospective HF cohorts is required to confirm clinical utility

Cite This Study

Zhu et al. (2026) conducted a cross-sectional in Acute decompensated heart failure with atrial fibrillation (n=59). Plasma AHNAK levels vs. Patients in sinus rhythm was evaluated on Atrial fibrillation discrimination (AUC 0.897, 95% CI 0.82-0.97). Plasma AHNAK levels strongly discriminated atrial fibrillation in patients with heart failure (AUC = 0.897; 95% CI 0.82-0.97), and AHNAK deficiency promoted atrial fibrotic remodeling.

synapsesocial.com/papers/6a65a825d3aea3239cd7895ahttps://doi.org/10.1186/s12916-026-05079-1
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