Associations between biomarkers and P-wave indices in relation to atrial fibrillation development in heart failure patients.

BACKGROUND

The predictive value of atrial conduction abnormalities, reflected by P-wave indices (PWIs), and their association with biomarkers signaling fibrosis for the development of atrial fibrillation (AF) in patients with heart failure (HF) remains underexplored.

OBJECTIVE

We aimed to investigate the associations among PWIs, fibrosis biomarkers, and the risk of incident AF in patients with HF.

METHODS

A total of 476 patients (mean age 74.6 years; 68% male) with new-onset or worsening HF were followed for 5 years. Fibrosis-associated biomarkers (tissue inhibitor of metalloproteinase 4, matrix metalloproteinase 2 [MMP-2], matrix metalloproteinase 3, matrix metalloproteinase 9, suppression of tumorigenicity 2, growth/differentiation factor 15 [GDF-15], galectin-3) were analyzed using the proximity extension assay. PWIs, including P-wave duration, P-wave amplitude in lead I, P-wave terminal force in lead V1, axis, and morphology, were derived from electrocardiograms processed with the Glasgow algorithm. Cox regression assessed associations among the biomarkers, PWIs, and incident AF.

RESULTS

During follow-up, 41 developed AF over 5 years. Low P-wave amplitude correlated negatively with GDF-15 (P < .001) and MMP-2 (P = .037) in leads I and II. 6 biomarkers were significantly associated with incident AF in adjusted analysis: tissue inhibitor of metalloproteinase 4 (P = .007), MMP-2 (P = .046), matrix metalloproteinase 3 (P = .007), suppression of tumorigenicity 2 (P = .003), GDF-15 (P = .001), and galectin-3 (P = .048). Among PWIs, P-wave axis of <0° (P = .021) and low P-wave amplitude in lead I (P = .036) were significantly associated with incident AF.

CONCLUSION

In patients with advanced HF, fibrotic biomarkers were associated with incident AF. Low P-wave amplitude and abnormal P-wave axis (<0°) were associated with incident AF. This may reflect an abnormal LA-conduction pathway and a displaced intra-atrial conduction pattern in advanced HF.