Cardiovascular

Association between human leukocyte antigen-DQ2/DQ8 positivity and incident atrial fibrillation in patients with heart failure with reduced ejection fraction.

Küçük U & Akşit E • Revista da Associacao Medica Brasileira (1992) • 2026

PubMed 42690360 DOI 10.1590/1806-9282.20260404

TL;DR

HLA-DQ2/DQ8 positivity is significantly associated with incident atrial fibrillation in heart failure with reduced ejection fraction patients, suggesting HLA-related immune-genetic susceptibility contributes to atrial electrical vulnerability.

Key Findings

Results

Incident atrial fibrillation occurred significantly more often in HFrEF patients than in controls over 24 months of follow-up.

Incident AF occurred in 16% (n=8) of the HFrEF group and 2% (n=1) of the control group
The study enrolled 50 HFrEF patients (LVEF <40%) and 50 age- and sex-matched controls
All subjects were in sinus rhythm at baseline
Follow-up duration was 24 months with incident AF as the primary endpoint

Results

All incident atrial fibrillation cases in the HFrEF group occurred exclusively within the HLA-positive subgroup.

20 of 50 HFrEF patients were HLA-positive (positive for DQ2 and/or DQ8)
AF incidence was 40% in HLA-positive HFrEF patients versus 0% in HLA-negative HFrEF patients (p=0.031)
All eight incident AF cases in the HFrEF group occurred within the HLA-positive subgroup
No incident AF cases occurred among HLA-negative HFrEF patients

Results

HLA-positive HFrEF patients exhibited a significantly higher atrial fibrillation risk compared to HLA-positive controls.

The difference in AF incidence between HLA-positive HFrEF patients and HLA-positive controls was statistically significant (p=0.0069)
This finding suggests that structural heart disease and genetic predisposition synergistically increase arrhythmic risk
The comparison specifically isolated the effect of HFrEF as a modifying factor within HLA-positive individuals

Conclusions

HLA-DQ2/DQ8 positivity is proposed as a potential novel biomarker for arrhythmic risk stratification in heart failure.

HLA-DQ2 and HLA-DQ8 alleles are described as 'established markers of immune-genetic dysregulation and chronic inflammation'
The authors propose that HLA-related immune-genetic susceptibility contributes to 'atrial electrical vulnerability'
The study positions HLA typing as a potential tool for identifying HFrEF patients at elevated risk for incident AF
The study design was a retrospective analysis based on a prospectively followed cohort

What This Means

This research suggests that certain immune-related genes, specifically the HLA-DQ2 and HLA-DQ8 variants already known to be associated with conditions like celiac disease, may also influence the risk of developing an irregular heart rhythm called atrial fibrillation (AF) in people who already have weakened heart muscle (heart failure with reduced ejection fraction, or HFrEF). In this study, 100 participants—50 with HFrEF and 50 healthy matched controls—were followed for two years to see who developed AF. Strikingly, all eight new AF cases among the HFrEF patients occurred only in those who carried the HLA-DQ2 or DQ8 gene variants, while none of the HLA-negative HFrEF patients developed AF during follow-up. The findings suggest that having both a structurally weakened heart and these particular immune-genetic markers may create a compounded vulnerability to developing abnormal heart rhythms. HLA-positive HFrEF patients were significantly more likely to develop AF than HLA-positive individuals without heart failure, pointing to a possible interaction between genetic immune factors and heart disease in driving arrhythmia risk. This research suggests that genetic testing for HLA-DQ2/DQ8 could one day help doctors identify which heart failure patients are at greatest risk for atrial fibrillation, potentially allowing for closer monitoring or earlier preventive interventions. However, the study was small (50 patients per group) and retrospective in nature, so larger prospective studies would be needed to confirm these findings before any clinical application could be considered.

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Citation

K&#xfc;&#xe7;&#xfc;k U, Ak&#x15f;it E. (2026). Association between human leukocyte antigen-DQ2/DQ8 positivity and incident atrial fibrillation in patients with heart failure with reduced ejection fraction.. Revista da Associacao Medica Brasileira (1992). https://doi.org/10.1590/1806-9282.20260404

Key Findings

What This Means

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