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

OBJECTIVE: Genetic susceptibility is increasingly recognized in cardiac arrhythmias. human leukocyte antigen-DQ2 and human leukocyte antigen-DQ8 alleles are established markers of immune-genetic dysregulation and chronic inflammation. This study investigated the association between human leukocyte antigen-DQ2/DQ8 positivity and incident atrial fibrillation in patients with heart failure with reduced ejection fraction. METHODS: This study was based on a prospectively followed cohort; the present retrospective analysis evaluated 50 heart failure with reduced ejection fraction patients (left ventricular ejection fraction <40%) and 50 age- and sex-matched controls. Participants were screened for human leukocyte antigen-DQ2/DQ8 alleles. All subjects were in sinus rhythm at baseline and followed for 24 months for the primary endpoint of incident atrial fibrillation. RESULTS: Incident atrial fibrillation occurred in 16% (n=8) of the heart failure with reduced ejection fraction group and 2% (n=1) of the control group. Among heart failure with reduced ejection fraction patients, human leukocyte antigen-positive status (positivity for DQ2 and/or DQ8) was found in 20 patients. Interestingly, all eight incident atrial fibrillation cases in the heart failure with reduced ejection fraction group occurred within the human leukocyte antigen-positive subgroup (40 vs. 0% in human leukocyte antigen-negative heart failure with reduced ejection fraction, p=0.031). human leukocyte antigen-positive heart failure with reduced ejection fraction patients exhibited a significantly higher atrial fibrillation risk compared to human leukocyte antigen-positive controls (p=0.0069), suggesting that structural heart disease and genetic predisposition synergistically increase arrhythmic risk. CONCLUSION: Human leukocyte antigen-DQ2/DQ8 positivity is significantly associated with incident atrial fibrillation in heart failure with reduced ejection fraction patients. These findings suggest human leukocyte antigen-related immune-genetic susceptibility contributes to atrial electrical vulnerability, positioning human leukocyte antigen typing as a potential novel biomarker for arrhythmic risk stratification in heart failure.