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Associations between biomarkers and P-wave indices in relation to atrial fibrillation development in heart failure
Zainu Nezami1, Amra Jujic2, Marcus Ohlsson3
1Department of Cardiology, Lund University, Malmö, Sweden; Department of Clinical Sciences, Lund University, Malmö, Sweden.
Insights
In heart failure patients, specific P-wave abnormalities and fibrosis biomarkers predict atrial fibrillation risk. Low P-wave amplitude and abnormal P-wave axis are linked to increased AF incidence.
Area of Science:
- Cardiology
- Electrophysiology
- Biomarker Research
Background:
- Atrial fibrillation (AF) risk in heart failure (HF) patients is significant.
- P-wave indices (PWIs) reflect atrial conduction but their link to fibrosis biomarkers and AF development in HF is unclear.
Purpose of the Study:
- To investigate associations between PWIs, fibrosis biomarkers, and incident AF in HF patients.
- To determine if PWIs and biomarkers can predict AF development in this population.
Main Methods:
- 476 patients with new-onset or worsening HF were followed for 5 years.
- Fibrosis biomarkers (e.g., MMP-2, GDF-15) and PWIs (e.g., P-wave amplitude, axis) were analyzed.
- Cox regression models assessed the relationship between biomarkers, PWIs, and incident AF.
Main Results:
- 41 patients developed AF over 5 years.
- Six fibrosis biomarkers (TIMP-4, MMP-2, MMP-3, ST2, GDF-15, Galectin-3) were significantly associated with incident AF.
- Low P-wave amplitude and an abnormal P-wave axis (<0°) were independently associated with increased AF risk.
Conclusions:
- Fibrotic biomarkers and specific P-wave abnormalities are associated with incident AF in advanced HF.
- Low P-wave amplitude and abnormal P-wave axis may indicate altered atrial conduction pathways.
- These findings highlight potential targets for AF risk stratification in HF 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.
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