# Proteomic biomarkers and biological pathways associated with atrial fibrillation in heart failure patients with reduced ejection fraction

## TL;DR

This study identifies proteomic differences in heart failure patients with and without atrial fibrillation, revealing potential biological pathways involved.

## Contribution

The study discovers 71 proteins and multiple biological pathways uniquely associated with atrial fibrillation in heart failure patients.

## Key findings

- 71 proteins were significantly associated with atrial fibrillation in heart failure patients.
- Pathways related to nervous system development and elastic fiber assembly were identified.
- Findings confirm and expand on known AF-related proteins and suggest new therapeutic targets.

## Abstract

Atrial fibrillation (AF) and heart failure (HF) are intertwined conditions with high mortality and impact on quality of life. The biological mechanisms at play in patients with HF with vs without AF may differ.

This study aimed to describe differences in circulating proteins with putative pathophysiological effects between HF with reduced ejection fraction (HFrEF) patients with and without AF.

We examined 377 patients with ambulant HFrEF and measured 4210 circulating proteins in baseline blood samples using an aptamer-based multiplex proteomic approach. Associations between AF (AF history or on baseline electrocardiogram) and the proteins were assessed using regression models adjusted for age, sex, kidney function, and duration of HF at baseline. Associations of AF-related proteins with biological processes were evaluated using enrichment analyses.

The median age [25th–75th percentile] was 64 years [55–72], 73% [274 of 377] were male, 28% [104 of 375] had New York Heart Association class III/IV, and 37% [139 of 377] had AF (either AF history [36%, 137 of 377] or AF on baseline electrocardiogram [8%, 30 of 374]). We found 71 proteins significantly associated with AF (false discovery rate < .05), including well-studied (eg, troponin T, insulin-like growth factor-binding protein 7, microfibril-associated glycoprotein 4, bone morphogenetic protein 10, angiopoietin 2) and lesser-studied proteins (eg, olfactomedin−like protein 3, keratocan, basigin) in the AF domain. Our pathway analysis revealed modules of proteins related to various underlying mechanisms, such as nervous system development, elastic fiber assembly, protein glycosylation, and ether lipid metabolism.

Patients with HFrEF with AF have distinct circulating proteomic profiles, and these differences are related to various biological mechanisms. This study provides an overview of the systemic biological pathways associated with AF in patients with HFrEF, confirms (pre-)clinical findings regarding AF-related proteins, and could inform future research in novel treatment targets and HFrEF-AF management after careful validation.