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Randomized Controlled Trial
. 2025 Jun;10(2):495-501.
doi: 10.1177/23969873241276358. Epub 2024 Aug 30.

Atrial cardiopathy biomarkers and atrial fibrillation in the ARCADIA trial

Hooman Kamel  1 , Mitchell Sv Elkind  2   3 , Richard A Kronmal  4 , W T Longstreth Jr  5   6   7 , Pamela Plummer  8 , Rebeca Aragon Garcia  2 , Joseph P Broderick  8 , Qi Pauls  9 , Jordan J Elm  9 , Fadi Nahab  10 , L Scott Janis  11 , Marco R Di Tullio  12 , Elsayed Z Soliman  13 , Jeff S Healey  14 , David L Tirschwell  5
Affiliations
Randomized Controlled Trial

Atrial cardiopathy biomarkers and atrial fibrillation in the ARCADIA trial

Hooman Kamel et al. Eur Stroke J. 2025 Jun.

Abstract

Background: ARCADIA compared apixaban to aspirin for secondary stroke prevention in patients with cryptogenic stroke and atrial cardiopathy. One possible explanation for the neutral result is that biomarkers used did not optimally identify atrial cardiopathy. We examined the relationship between biomarker levels and subsequent detection of AF, the hallmark of atrial cardiopathy.

Methods: Patients were randomized if they met criteria for atrial cardiopathy, defined as P-wave terminal force >5000 μV*ms in ECG lead V1 (PTFV1), NT-proBNP >250 pg/mL, or left atrial diameter index (LADI) ⩾3 cm/m2. For this analysis, the outcome was AF detected per routine care.

Results: Of 3745 patients who consented to screening for atrial cardiopathy, 254 were subsequently diagnosed with AF; 96 before they could be randomized and 158 after randomization. In unadjusted analyses, ln(NT-proBNP) (RR per SD, 1.99; 95% CI, 1.85-2.13), PTFV1 (RR per SD, 1.15; 95% CI, 1.03-1.28) and LADI (RR per SD, 1.34; 95% CI, 1.20-1.50) were associated with AF. In a model containing all 3 biomarkers, demographics, and AF risk factors, age (RR per 10 years, 1.24; 95% CI, 1.09-1.41), ln(NT-proBNP) (RR per SD, 1.88; 95% CI, 1.67-2.11) and LADI (RR per SD, 1.25; 95% CI, 1.14-1.37) were associated with AF. These three variables together had a c-statistic of 0.82 (95% CI, 0.79-0.85) but only modest calibration. Discrimination was attenuated in sensitivity analyses of patients eligible for randomization who may have been more closely followed for AF.

Conclusions: Biomarkers used to identify atrial cardiopathy in ARCADIA were moderately predictive of subsequent AF.

Keywords: Atrial fibrillation; atrial cardiomyopathy; atrial cardiopathy; atrial myopathy; stroke.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Kamel reports serving as Deputy Editor for JAMA Neurology; serving on clinical trial steering/executive committees for the STROKE-AF (Medtronic), LIBREXIA-AF (Janssen), and LAAOS-4 (Boston Scientific) trials; serving as a consultant or endpoint adjudication committee member for AbbVie, AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and household ownership interests in TETMedical, Spectrum Plastics Group, and Ascential Technologies. Dr. Healey reports research grants and speaking fees from BMS/Pfizer, Servier, Boston Scientific, and Medtronic. Dr. Kasner reports grant funding from Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Genentech, Medtronic, and Diamedica, consulting fees from AstraZeneca, Abbie, and Novo Nordisk, and royalties from UpToDate. Dr. Elkind reports employment by the American Heart Association, royalties from UpToDate for chapters on stroke, and honoraria for lectures from the Atria Academy for Science and Medicine. The other authors report no conflicts of interest.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Calibration of atrial cardiopathy biomarkers for predicting AF in ARCADIA. Each open circle represents 1 of 20 groups of ARCADIA trial participants. Patients were grouped by their predicted probability of atrial fibrillation (AF) based on a relative risk regression model comprised of NT-proBNP, left atrial dimension index, and P-wave terminal force in ECG lead V1. The circle’s position on the x-axis represents the group’s predicted probability of atrial fibrillation. The circle’s position on the y-axis represents the actual proportion of patients in the group who developed atrial fibrillation. The dashed blue line represents perfect calibration
See this image and copyright information in PMC

Comment in

References

    1. Goette A, Kalman JM, Aguinaga L, et al. EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication. Heart Rhythm 2017; 14: e3–e40. - PMC - PubMed
    1. Hirsh BJ, Copeland-Halperin RS, Halperin JL. Fibrotic atrial cardiomyopathy, atrial fibrillation, and thromboembolism: mechanistic links and clinical inferences. J Am Coll Cardiol 2015; 65: 2239–2251. - PubMed
    1. Kamel H, Okin PM, Elkind MS, et al. Atrial fibrillation and mechanisms of stroke: time for a new model. Stroke 2016; 47: 895–900. - PMC - PubMed
    1. Kamel H, Longstreth Wt, Jr, Tirschwell DL, et al. The AtRial cardiopathy and antithrombotic drugs in prevention after cryptogenic stroke randomized trial: Rationale and methods. Int J Stroke 2019; 14: 207–214. - PMC - PubMed
    1. Kamel H, Longstreth WT, Jr, Tirschwell DL, et al. Apixaban to prevent recurrence after cryptogenic stroke in patients with atrial cardiopathy: the ARCADIA randomized clinical trial. JAMA 2024; 331(7): 573–581. - PMC - PubMed

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