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Multicenter Study
. 2025 Sep 17;26(1):272.
doi: 10.1186/s12931-025-03342-2.

ECG-based identification of COPD patients at risk for atrial fibrillation and its impact on adverse clinical outcomes-a subgroup analysis of the prospective multicenter COSYCONET cohort

Martin Eichenlaub  1   2 , Björn Christian Frye  3 , Heiko Lehrmann  4 , Frank Biertz  5 , Amir Sherwan Jadidi  4   6 , Klaus Kaier  7 , Thomas Melzer  8 , Peter Alter  9 , Henrik Watz  10 , Benjamin Waschki  10   11 , Barbara Christine Weckler  12 , Franziska Christina Trudzinski  13 , Julia Dorothea Michels-Zetsche  13 , Frederik Trinkmann  13 , Felix Josef-Friedrich Herth  13 , Hans-Ulrich Kauczor  14 , Kathrin Kahnert  8 , Rudolf Jörres  15 , Robert Bals  16   17 , Dirk Westermann  4 , Thomas Arentz  4 , Claus Franz Vogelmeier  9 , Daiana Stolz  3 , Sebastian Fähndrich  18 ; German COSYCONET cohort
Collaborators, Affiliations
Multicenter Study

ECG-based identification of COPD patients at risk for atrial fibrillation and its impact on adverse clinical outcomes-a subgroup analysis of the prospective multicenter COSYCONET cohort

Martin Eichenlaub et al. Respir Res. .

Abstract

Background: Atrial fibrillation (AF) frequently occurs in patients with chronic obstructive pulmonary disease (COPD) and is associated with adverse clinical outcomes. We aimed to identify patients at risk for AF using amplified p-wave duration (APWD) analysis on electrocardiogram (ECG) as non-invasive tool to diagnose an atrial cardiomyopathy (AtCM) which is an established risk factor for AF.

Methods: This subgroup analysis of the prospective COSYCONET cohort included 2,385 COPD patients from 31 study centers with baseline sinus rhythm ECG and at least one follow-up examination. Of these, 73 patients showed AF during follow-up and were propensity-score matched to controls. APWD was measured at baseline and future major adverse cardiac and cerebrovascular events (MACCE) and health related outcome were assessed.

Results: 219 COPD patients (70 [64-74] years, 79.5% male) were analyzed during a follow-up of 586 (210-1137) days. APWD was significantly longer in patients with AF occurrence compared to controls (132 [125-141] ms vs. 124 [117-133] ms, p < 0.001) and remained significant in multivariate regression analysis (OR: 1.05 [1.01-1.09], p = 0.03). An APWD ≥ 131 ms was identified as best cut-off for AF prediction (62% sensitivity, 70% specificity, OR: 3.91 [2.58 to 5.95], p < 0.001). Patients with AF had a significantly higher MACCE rate (24.7% versus 8.2%, p = 0.001) and a significantly lower physical activity score (1,074 [264-4,776] vs. 2,706 [975-7,339], p = 0.008).

Conclusions: This study demonstrates that ECG-based AtCM diagnosis identifies COPD patients at risk for AF, which was associated with a substantially elevated MACCE rate and a significantly reduced physical activity. This easy, cost-effective and widely available digital biomarker might enable early therapy initiation and prevention of adverse clinical outcomes.

Trial registration: NCT01245933 on Clinical-Trials.gov (Registration date: 22.11.2010).

Keywords: Atrial fibrillation; Biomarker; COPD; Electrocardiography; MACCE; Screening.

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Conflict of interest statement

Declarations. Ethics approval statement and consent to participate: The study protocol was approved by the central ethical committee in Marburg (Ethikkommission FB Medizin Marburg, approval number 200/09) and the respective local ethical committees: Bad Reichenhall (Ethikkommission Bayerische Landesärztekammer); Berlin (Ethikkommission Ärztekammer Berlin); Bochum (Ethikkommission Medizinische Fakultät der RUB); Borstel (Ethikkommission Universität Lübeck); Coswig (Ethikkommission TU Dresden); Donaustauf (Ethikkommission Universitätsklinikum Regensburg); Essen (Ethikkommission Medizinische Fakultät Duisburg-Essen); Gießen (Ethikkommission Fachbereich Medizin); Greifswald (Ethikkommission Universitätsmedizin Greifswald); Großhansdorf (Ethikkommission Ärztekammer Schleswig–Holstein); Hamburg (Ethikkommission Ärztekammer Hamburg); MHH Hannover/Coppenbrügge (MHH Ethikkommission); Heidelberg Thorax/Uniklinik (Ethikkommission Universität Heidelberg); Homburg (Ethikkommission Saarbrücken); Immenhausen (Ethikkommission Landesärztekammer Hessen); Kiel (Ethikkommission Christian-Albrechts-Universität zu Kiel); Leipzig (Ethikkommission Universität Leipzig); Löwenstein (Ethikkommission Landesärztekammer Baden-Württemberg); Mainz (Ethikkommission Landesärztekammer Rheinland-Pfalz); München LMU/Gauting (Ethikkommission Klinikum Universität München); Nürnberg (Ethikkommission Friedrich-Alexander-Universität Erlangen Nürnberg); Rostock (Ethikkommission Universität Rostock); Berchtesgadener Land (Ethikkommission Land Salzburg); Schmallenberg (Ethikkommission Ärztekammer Westfalen-Lippe); Solingen (Ethikkommission Universität Witten-Herdecke); Ulm (Ethikkommission Universität Ulm); Würzburg (Ethikkommission Universität Würzburg). The study was performed in accordance with the declaration of Helsinki, and all patients provided written informed consent prior to study inclusion. Consent for publication: Not applicable. Competing interests: Martin Eichenlaub, Heiko Lehrmann, Frank Biertz, Amir S. Jadidi, Klaus Kaier, Henrik Watz, Benjamin Waschki and Thomas Arentz have no competing interests. Björn C. Frye received lecture and advisory fees from Advita Lifescience GmbH, Astra Zeneca, Boehringer Ingelheim and Vifor outside the submitted work. Björn C. Frye received research grants from Advita Lifescience GmbH and BMS outside the submitted work. Björn C. Frye is supported by the Berta-Ottenstein-Program for Advanced Clinician Scientists from the Faculty of Medicine, University of Freiburg. Thomas Melzer is co-founder and scientific consultant of the deep tech startup AICU GmbH, Heilbronn. The present results are not related to the company's activities. He continued to receive travel allowances and speaking fees from AstraZeneca outside the submitted work. He is currently a Fellow of the Collège des Ingénieurs, Munich. Peter Alter received unrestricted grants from GSK, Chiesi, AstraZeneca and Sanofi, consulting fees (advisory board) from Sanofi, honoraria for presentation from StreamedUp GmbH and travel support from Sanofi and Boehringer Ingelheim outside the submitted work. Barbara Christine Weckler performed unpaid contract work for AstraZeneca outside the submitted work. She is Chair of the Scientific Advisory Board of the German Lung Foundation and her research is supported by the German Federal Ministry of Education and Research (BMBF). Franziska C. Trudzinski received an innovation fund (funding code: 01NVF19023) of the Federal Joint Committee (G-BA) according to §92(1) Social Code Book V and personal fees from Boehringer Ingelheim, Chiesi, GSK, Grifols, Novartis, CSL Behring, Streamed up, RG Gesellschaft für Information und Organisation mbH, Knorr Stiftung, AstraZeneca and Apontis Pharma outside the submitted work. Advisory board: CSL Behring, GSK outside the submitted work. Julia D. Michels-Zetsche reports a relationship with the Federal Joint Committee of Doctors Hospitals and Health Insurers that includes: funding grants for the PRiVENT project as well as payment or honoraria for lectures from AstraZeneca and reimbursement of travel expenses from CSL Behring outside the submitted work. Frederik Trinkmann reports grants from AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, Novartis, Roche, BMBF, DZL, Markedsmodningsfonden and E + H Knorr Stiftung, as well as consulting fees and honoraria from AstraZeneca, Berlin Chemie, Boehringer Ingelheim, BMS, Chiesi, Fisher & Paykel, GSK, Janssen-Cilag, Merck Healthcare, Novartis, Omron, OM-Pharma, Roche, Sanofi, Aventis and Thorasys, and travel support from AstraZeneca, Actelion, Bayer, Berlin Chemie, Boehringer Ingelheim, Chiesi, Mundipharma, Novartis, Pfizer and TEVA outside the submitted work. Felix J. F. Herth received fees for lectures from CSL Behring, Grifols, AstraZeneca, BerlinChemie, GSK and Chiesi outside the submitted work. Felix J. F. Herth´s research is supported by the German Federal Ministry of Education and Research (BMBF). Hans-Ulrich Kauczor received fees for lectures and grant support to the institution from Siemens, Philips, and Boehringer Ingelheim outside the submitted work. Hans-Ulrich Kauczor serves on advisory boards of Median and Contextflow outside the submitted work. His research is supported by German Federal Ministry of Education and Research (BMBF) and by the European Commission (EU4Health). Kathrin Kahnert reports personal fees from Astra Zeneca, Berlin Chemie, Insmed, Chiesi, Santis, Boehringer Ingelheim outside the submitted work. Rudolf A. Jörres received fees for lectures from Chiesi, AstraZeneca and GSK outside the submitted work. Robert Bals received grants from Sander Stiftung, Schwiete Stiftung, DFG, BMBF, Krebshilfe, State of Saarland outside the submitted work. Advisory board, consulting fees and travel support: AstraZeneca, CSL, Novartis, Regeneron, Grifols outside the submitted work. He is one of the Editors in Chief of Respiratory Research. Dirk Westermann received honorary from Abiomed, AstraZeneca, Edwards, Meril, Novartis outside the submitted work. Claus F. Vogelmeier gave presentations at symposia and/or served on scientific advisory boards sponsored by Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GSK, Grifols, Insmed, Menarini, Novartis, Nuvaira, Roche, and Sanofi outside the submitted work. Daiana Stolz received payments or honoraria for lectures, presentations, advisory boards, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Berlin-Chemie/Menarini, Boehringer Ingelheim, Chiesi, CSL Behring, Curetis, GSK, Merck, MSD, Novartis, Roche, Sanofi and Vifor outside the submitted work. Sebastian Fähndrich received fees for lectures and travel support from CSL Behring, Grifols, AstraZeneca, BerlinChemie. Sebastian Fähndrich’s research is supported by the German Federal Ministry of Education and Research (BMBF) and by the European Union (ISIDORe).

Figures

Fig. 1
Fig. 1
Overview of the overall cohort and the study population. AF, atrial fibrillation; ECG, electrocardiogram; SR, sinus rhythm; FU, follow-up * Individuals aged ≥ 40 years with stable COPD, excluding patients with a lung tumor, a moderate or severe exacerbation within the last four weeks prior to inclusion, or a history of major lung surgery
Fig. 2
Fig. 2
Amplified p-wave duration (APWD) measurement (only the limb leads are illustrated) between earliest onset and latest end of the p-wave in any of the ECG leads in two example patients with an APWD of 104 ms (Panel A) and an APWD of 181 ms (Panel B), respectively
Fig. 3
Fig. 3
Differentiation between patients with and without atrial fibrillation (AF) during follow-up using ECG-based atrial cardiomyopathy diagnosis. Panel A Amplified p-wave duration (APWD) between patients with (study group) and without (control group) AF. Whiskers depict median with 25% and 75% interquartile range. Panel B Definition of an APWD cut-off of ≥131 ms as the best predictor for AF occurrence with an area under the curve (AUC) of 0.680. Panel C Accurate differentiation between patients with (sensitivity of 62%) and without (specificity of 70%) AF risk using APWD cut-off of ≥131 ms
See this image and copyright information in PMC

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