Predictors of Atrial Fibrillation in Patients With Stroke Attributed to Large- or Small-Vessel Disease: A Prespecified Secondary Analysis of the STROKE AF Randomized Clinical Trial

Abstract

Importance: The Stroke of Known Cause and Underlying Atrial Fibrillation (STROKE AF) trial found that approximately 1 in 8 patients with recent ischemic stroke attributed to large- or small-vessel disease had poststroke atrial fibrillation (AF) detected by an insertable cardiac monitor (ICM) at 12 months. Identifying predictors of AF could be useful when considering an ICM in routine poststroke clinical care.

Objective: To determine the association between commonly assessed risk factors and poststroke detection of new AF in the STROKE AF cohort monitored by ICM.

Design, setting, and participants: This was a prespecified analysis of a randomized (1:1) clinical trial that enrolled patients between April 1, 2016, and July 12, 2019, with primary follow-up through 2020 and mean (SD) duration of 11.0 (3.0) months. Eligible patients were selected from 33 clinical research sites in the US. Patients had an index stroke attributed to large- or small-vessel disease and were 60 years or older or aged 50 to 59 years with at least 1 additional stroke risk factor. A total of 496 patients were enrolled, and 492 were randomly assigned to study groups (3 did not meet inclusion criteria, and 1 withdrew consent). Patients in the ICM group had the index stroke within 10 days before insertion. Data were analyzed from October 8, 2021, to January 28, 2022.

Interventions: ICM monitoring vs site-specific usual care (short-duration external cardiac monitoring).

Main outcomes and measures: The ICM device automatically detects AF episodes 2 or more minutes in length; episodes were adjudicated by an expert committee. Cox regression multivariable modeling included all parameters identified in the univariate analysis having P values <.10. AF detection rates were calculated using Kaplan-Meier survival estimates.

Results: The analysis included the 242 participants randomly assigned to the ICM group in the STROKE AF study. Among 242 patients monitored with ICM, 27 developed AF (mean [SD] age, 66.6 [9.3] years; 144 men [60.0%]; 96 [40.0%] women). Two patients had missing baseline data and exited the study early. Univariate predictors of AF detection included age (per 1-year increments: hazard ratio [HR], 1.05; 95% CI, 1.01-1.09; P = .02), CHA2DS2-VASc score (per point: HR, 1.54; 95% CI, 1.15-2.06; P = .004), chronic obstructive pulmonary disease (HR, 2.49; 95% CI, 0.86-7.20; P = .09), congestive heart failure (CHF; with preserved or reduced ejection fraction: HR, 6.64; 95% CI, 2.29-19.24; P < .001), left atrial enlargement (LAE; HR, 3.63; 95% CI, 1.55-8.47; P = .003), QRS duration (HR, 1.02; 95% CI, 1.00-1.04; P = .04), and kidney dysfunction (HR, 3.58; 95% CI, 1.35-9.46; P = .01). In multivariable modeling (n = 197), only CHF (HR, 5.06; 95% CI, 1.45-17.64; P = .05) and LAE (HR, 3.32; 1.34-8.19; P = .009) remained significant predictors of AF. At 12 months, patients with CHF and/or LAE (40 of 142 patients) had an AF detection rate of 23.4% vs 5.0% for patients with neither (HR, 5.1; 95% CI, 2.0-12.8; P < .001).

Conclusions and relevance: Among patients with ischemic stroke attributed to large- or small-vessel disease, CHF and LAE were associated with a significantly increased risk of poststroke AF detection. These patients may benefit most from the use of ICMs as part of a secondary stroke prevention strategy. However, the study was not powered for clinical predictors of AF, and therefore, other clinical characteristics may not have reached statistical significance.

Trial registration: ClinicalTrials.gov Identifier: NCT02700945.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Schwamm reported receiving consultant fees from Genentech, Life Image, Massachusetts Department of Public Health Stroke Systems of Care; data safety board member fees from Penumbra and Diffusion Pharma; and grants from Medtronic, National Institute of Neurological Disorders and Stroke (NINDS), Massachusetts General Hospital, Genentech, and NINDS StrokeNet outside the submitted work. Dr Kamel reported receiving funding as principal investigator for the National Institutes of Health–funded ARCADIA trial; as Deputy Editor for JAMA Neurology; as a clinical trial steering/executive committee member for Medtronic, Janssen, and Javelin Medical; and as an end point adjudication committee member for AstraZeneca, Novo Nordisk, and Boehringer Ingelheim; he also reported ownership interest in TETMedical Inc. Dr Granger reported receiving personal fees and grants from Boehringer Ingelheim, Bristol Myers Squibb, Pfizer, Janssen, Bayer, and Anthos and consulting/research funding from Medtronic, Daiichi Sankyo, and Boston Scientific. Dr Piccini reported receiving grants from the National Heart, Lung and Blood Institute, the American Heart Association, the Association for the Advancement of Medical Instrumentation, Bayer, Boston Scientific, Abbott, iRhythm, and Philips and personal/consultant fees from AbbVie, Allergan, Abbott, ARCA Biopharma, Biotronik, LivaNova, Bristol Myers Squibb, Element Science, Boston Scientific, Medtronic, Myokardia, Nocturnal Product Development, UpToDate, ElectroPhysiology Frontiers, Record, Itamar, Sanofi, Philips, and Milestone outside the submitted work. Dr Katz reported receiving grants from Siemens Healthineers and the National Institutes of Health and research funding from Medtronic. Dr Sethi reports receiving consulting, promotional speaking, and research funding from Medtronic. Dr Sidorov reported receiving grants from Medtronic during the conduct of the study. Dr Kasner reported receiving grants from Medtronic, AbbVie, AstraZeneca, J&J, Diamedica, Bristol Myers Squibb, Genentech, WL Gore, and Bayer; personal fees from Medtronic and AstraZeneca; and royalties from UpToDate and Elsevier outside the submitted work. Dr Franco reported being an employee of and a shareholder in Medtronic outside the submitted work. Dr Ziegler reported receiving fees as an employee and shareholder from Medtronic during the conduct of the study. Dr Bernstein reported receiving grants and personal fees from Medtronic during the conduct of the study; serving as co–principal investigator for Medtronic; and receiving consulting fees, paid steering committee membership fees, promotional speaking fees, and research funding from Medtronic, Boehringer Ingelheim, Pfizer, Bristol Myers Squibb, Abbott, Amag Pharma, AbbVie, and Astra Zeneca. No other disclosures were reported.

Figures

Figure.. Rate of Atrial Fibrillation (AF) Detection at 12 Months Among Patients With Congestive Heart Failure (CHF) or Left Atrial Enlargement (LAE)

Increased AF detection in patients with CHF and/or LAE in participants randomized to insertable cardiac monitor (ICM) in the Stroke of Known Cause and Underlying Atrial Fibrillation (STROKE AF) trial through 12 months compared with participants without either condition (23.4% vs 5%; P < .001).