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

Nezami, Zainu LU ; Jujic, Amra LU orcid ; Ohlsson, Marcus LU orcid ; Magnusson, Martin H. LU orcid ; Holm Isholth, Hannes LU and Platonov, Pyotr LU (2025) In Heart Rhythm
Abstract

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... (More)

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.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Heart Rhythm
publisher
Elsevier
external identifiers
  • pmid:41241107
ISSN
1556-3871
DOI
10.1016/j.hrthm.2025.11.015
language
English
LU publication?
yes
id
918c8d55-da8f-4121-89e4-03c48523c057
date added to LUP
2025-11-16 11:05:23
date last changed
2025-11-17 13:29:49
@article{918c8d55-da8f-4121-89e4-03c48523c057,
  abstract     = {{<p>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.</p><p>OBJECTIVE: We aim to investigate the associations between PWI, fibrosis biomarkers, and the risk of incident AF in patients with HF.</p><p>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.</p><p>RESULTS: During follow up, 41 developed AF over 5 years. Low P-wave amplitude correlated negatively with GDF-15 (p &lt; 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 &lt;0° (p = 0.021) and low P-wave amplitude in lead I (p=0.036) were significantly associated with incident AF.</p><p>CONCLUSIONS: In advanced HF patients, fibrotic biomarkers were associated with incident AF. Low P-wave and abnormal P-wave axis (&lt;0 degree) were associated with incident AF. This may reflect abnormal LA-conduction pathway and displaced intra-atrial conduction pattern in advanced HF.</p>}},
  author       = {{Nezami, Zainu and Jujic, Amra and Ohlsson, Marcus and Magnusson, Martin H. and Holm Isholth, Hannes and Platonov, Pyotr}},
  issn         = {{1556-3871}},
  language     = {{eng}},
  month        = {{11}},
  publisher    = {{Elsevier}},
  series       = {{Heart Rhythm}},
  title        = {{Associations between biomarkers and p-wave indices in relation to atrial fibrillation development in heart failure patients}},
  url          = {{http://dx.doi.org/10.1016/j.hrthm.2025.11.015}},
  doi          = {{10.1016/j.hrthm.2025.11.015}},
  year         = {{2025}},
}