Atrial cardiopathy biomarkers and atrial fibrillation in the ARCADIA trial

Hooman Kamel; Mitchell Sv Elkind; Richard A Kronmal; W T Longstreth Jr; Pamela Plummer; Rebeca Aragon Garcia; Joseph P Broderick; Qi Pauls; Jordan J Elm; Fadi Nahab; L Scott Janis; Marco R Di Tullio; Elsayed Z Soliman; Jeff S Healey; David L Tirschwell

doi:10.1177/23969873241276358

Atrial cardiopathy biomarkers and atrial fibrillation in the ARCADIA trial

Eur Stroke J. 2024 Aug 30:23969873241276358. doi: 10.1177/23969873241276358. Online ahead of print.

Authors

Hooman Kamel¹, Mitchell Sv Elkind^{2

3}, Richard A Kronmal⁴, W T Longstreth Jr^{5

6

7}, Pamela Plummer⁸, Rebeca Aragon Garcia², Joseph P Broderick⁸, Qi Pauls⁹, Jordan J Elm⁹, Fadi Nahab¹⁰, L Scott Janis¹¹, Marco R Di Tullio¹², Elsayed Z Soliman¹³, Jeff S Healey¹⁴, David L Tirschwell⁵

Affiliations

¹ Clinical and Translational Neuroscience Unit, Department of Neurology and Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
² Department of Neurology, Columbia University, New York, NY, USA.
³ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
⁴ Departments of Biostatistics, University of Washington, Seattle, WA, USA.
⁵ Neurology, University of Washington, Seattle, WA, USA.
⁶ Medicine, University of Washington, Seattle, WA, USA.
⁷ Epidemiology, University of Washington, Seattle, WA, USA.
⁸ Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
⁹ Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA.
¹⁰ Departments of Neurology and Pediatrics, Emory University, Atlanta, GA, USA.
¹¹ National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
¹² Division of Cardiology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
¹³ Epidemiological Cardiology Research Center, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
¹⁴ Population Health Research Institute, McMaster University, Hamilton, ON, Canada.

PMID: 39212178
DOI: 10.1177/23969873241276358

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.