TY - JOUR
T1 - Associations between biomarkers and p-wave indices in relation to atrial fibrillation development in heart failure patients
AU - Nezami, Zainu
AU - Jujic, Amra
AU - Ohlsson, Marcus
AU - Magnusson, Martin H.
AU - Holm Isholth, Hannes
AU - Platonov, Pyotr
PY - 2025/11/13
Y1 - 2025/11/13
N2 - BACKGROUND: The predictive value of atrial conduction abnormalities, reflected by P-wave indices (PWI), and their association with biomarkers signaling fibrosis for the development of atrial fibrillation (AF) in patients with heart failure (HF) remains underexplored.OBJECTIVE: We aim to investigate the associations between PWI, 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 (TIMP-4, MMP-2, MMP-3, MMP-9, ST-2, GDF-15, Gal-3) were analyzed using proximity extension assay. PWI, including P-wave duration, P-wave amplitude in lead I, P-wave terminal force in V1, axis and morphology were derived from ECGs processed with the Glasgow algorithm. Cox regression assessed associations between the biomarkers, PWI, and incident AF.RESULTS: During follow up, 41 developed AF over 5 years. Low P-wave amplitude correlated negatively with GDF-15 (p < 0.001) and MMP-2 (p = 0.037) in lead I and II. Six biomarkers were significantly associated with incident AF in adjusted analysis: TIMP-4 (p=0.007), MMP-2 (p=0.046), MMP-3 (p=0.007), ST-2 (p=0.003), GDF-15 (p=0.001), and Gal-3 (p=0.048). Among PWI, P-wave axis <0° (p = 0.021) and low P-wave amplitude in lead I (p=0.036) were significantly associated with incident AF.CONCLUSIONS: In advanced HF patients, fibrotic biomarkers were associated with incident AF. Low P-wave and abnormal P-wave axis (<0 degree) were associated with incident AF. This may reflect abnormal LA-conduction pathway and displaced intra-atrial conduction pattern in advanced HF.
AB - BACKGROUND: The predictive value of atrial conduction abnormalities, reflected by P-wave indices (PWI), and their association with biomarkers signaling fibrosis for the development of atrial fibrillation (AF) in patients with heart failure (HF) remains underexplored.OBJECTIVE: We aim to investigate the associations between PWI, 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 (TIMP-4, MMP-2, MMP-3, MMP-9, ST-2, GDF-15, Gal-3) were analyzed using proximity extension assay. PWI, including P-wave duration, P-wave amplitude in lead I, P-wave terminal force in V1, axis and morphology were derived from ECGs processed with the Glasgow algorithm. Cox regression assessed associations between the biomarkers, PWI, and incident AF.RESULTS: During follow up, 41 developed AF over 5 years. Low P-wave amplitude correlated negatively with GDF-15 (p < 0.001) and MMP-2 (p = 0.037) in lead I and II. Six biomarkers were significantly associated with incident AF in adjusted analysis: TIMP-4 (p=0.007), MMP-2 (p=0.046), MMP-3 (p=0.007), ST-2 (p=0.003), GDF-15 (p=0.001), and Gal-3 (p=0.048). Among PWI, P-wave axis <0° (p = 0.021) and low P-wave amplitude in lead I (p=0.036) were significantly associated with incident AF.CONCLUSIONS: In advanced HF patients, fibrotic biomarkers were associated with incident AF. Low P-wave and abnormal P-wave axis (<0 degree) were associated with incident AF. This may reflect abnormal LA-conduction pathway and displaced intra-atrial conduction pattern in advanced HF.
U2 - 10.1016/j.hrthm.2025.11.015
DO - 10.1016/j.hrthm.2025.11.015
M3 - Article
C2 - 41241107
SN - 1556-3871
JO - Heart Rhythm
JF - Heart Rhythm
ER -
