Arrhythmias and sudden death Original research Heart: first published as 10.1136/heartjnl-2020-316904 on 3 July 2020. Downloaded from Continuous electrocardiography for detecting atrial fibrillation beyond 1 year after stroke in primary care Louise Feldborg Lyckhage ,1 Morten Lock Hansen,2,3 Jens Christian Toft,4 Susanne Lis Larsen,5 Bente Brendorp,6 Ari Mohammad Ali,1 Troels Wienecke1,7 ► Additional material is ABSTRACT The long- term efforts to prevent recurrent stroke published online only. To view Background and purpose The diagnostic benefit are typically handled at patients’ general practice please visit the journal online (http:// dx. doi. org/ 10. 1136/ of using continuous ECG (cECG) for poststroke atrial (GP) clinic. Guidelines for the elderly population heartjnl- 2020- 316904). fibrillation (AF) screening in a primary care setting is include opportunistic pulse palpation followed by unclear. We aimed to assess the diagnostic yield from 12- lead ECG in case of irregular pulse.8 Never- 1 Department of Neurology, screening patients who previously had a stroke with a theless, there are currently no guidelines specific Zealand University Hospital, 7-day Holter monitor. to primary care poststroke AF screening. Brach- Roskilde, Denmark 6 2Department of Cardiology, Methods Patients older than 49 years, naive to AF, mann et al showed that monitoring patients with Copenhagen University Hospital with an ischaemic stroke over 1 year before enrolment cryptogenic stroke with implantable loop recorder Herlev and Gentofte, Hellerup, were included. In a primary care setting, all patients detected AF in 30% after 3 years compared with Denmark 3 were screened for AF using pulse palpation, 12-lead ECG The Cardiovascular Research 12.4% after 1 year. Thus, AF could be markedly Centre, Copenhagen University and 7-day Holter monitoring. Further, NT-proBNP was underdiagnosed even years after stroke without the Hospital, Gentofte, Denmark determined at baseline. use of effective systematic screening methods. Using 4 Department of Cardiology Results 7- day Holter monitoring uncovered AF in 17 implantable loop recorders in all patients who had a and Endocrinology, Slagelse of 366 patients (4.6% (95% CI 2.7 to 7.3)). The number Hospital, Slagelse, Denmark stroke does, however, seem unrealistic. 5Borup and Viby General needed to screen was 22 patients (14–37). 12-lead This is the first study to investigate the role of Practice, General practice ECG uncovered AF in 3 patients (0.82% (95% CI 0.17 external cECG as an AF screening tool in a primary in Region Zealand, Borup, to 2.4)), and 122 patients had irregular pulse during care setting beyond the first year after ischaemic Denmark 6 pulse palpation (33.5% (95% CI 28.7 to 38.2)). When stroke. In collaboration with GP clinics, our primary Department of Cardiology, North Zealand Hospital, using 7-day Holter monitoring as reference standard, the aim was to determine the proportion of newly diag- Hilleroed, Denmark sensitivity of pulse palpation and 12-lead ECG was 47% nosed AF by use of 7- day Holter monitoring. The 7 Department of Clinical (95% CI 23% to 72%) and 18% (95% CI 4% to 43%). secondary aims included assessment of the sensi- Medicine, University of http://heart.bmj.com/ High levels (≥400 pg/mL) of NT- proBNP versus low tivity of pulse palpation and 12- lead ECG, using Copenhagen, Copenhagen, Denmark levels (≤200 pg/mL) were not associated with AF in the 7- day Holter monitoring as a reference standard, univariate analysis nor when adjusted for age (OR 2.4 and assessment of the association of high versus low Correspondence to (95% CI 0.5 to 8.4) and 1.6 (95% CI 0.3 to 6.0)). levels of N- terminal Pro- Brain Natriuretic Peptide Dr Louise Feldborg Lyckhage Conclusions A relevant proportion of patients with (NT- proBNP) with the risk of AF. and Dr Louise Feldborg stroke more than 1 year before inclusion were diagnosed Lyckhage, Neurology, Zealand with AF through 7-day Holter monitoring. Given the University Hospital Roskilde, 4000 Roskilde, Denmark; low sensitivities of pulse palpation and 12-lead ECG, METHODS on September 28, 2021 by guest. Protected copyright. llyckhage@ hotmail.com, additional cECG may be considered during poststroke Design, setting and data collection llyckhage@ hotmail.com primary care follow- up. This prospective cohort study was a collabora- tion between the Neurovascular Center, Zealand Received 15 March 2020 Revised 16 May 2020 University Hospital (NVC) and two GP clinics Accepted 22 May 2020 in the Region of Zealand, Denmark (Borup and Published Online First INTRODUCTION Havdrup). Patient recruitment began in November 3 July 2020 Ischaemic stroke is a prevalent and potentially 2016 at Borup GP clinic and in November 2017 at debilitating condition, where identification and Havdrup GP clinic. We initially aimed to conduct treatment of potential risk factors of recurrent all recruitment and data collection via the primary stroke are crucial.1 Atrial fibrillation (AF) is one of sector. Through a protocol amendment in March the most important risk factors 'and is associated 2018, we improved recruitment rate by expanding with a five- fold increased risk of ischemic stroke.2 the source population to all participants previously This risk is reducible by converting therapy from admitted to the NVC and set up facilities for data antiplatelet to oral anticoagulant treatment (OAC).3 collection at the latter. Due to changes in the hospital © Author(s) (or their Effective AF detection after stroke is challenging patient record systems, data were not available for employer(s)) 2021. Re- use 4 permitted under CC BY- NC. No since AF is often paroxysmal and asymptomatic. participants with stroke beyond 10 years. Conse- commercial re- use. See rights Randomised clinical trials and meta- analyses have quently, we restricted time since last stroke to 1–10 and permissions. Published shown that increasing the time of ECG monitoring years prior to inclusion for all participants, meaning by BMJ. in the early phase after ischaemic stroke uncovers some of the participants recruited via the GP clinic 5–7 To cite: Lyckhage LF, progressively more AF. Consequently, current in Borup were excluded from analysis. Enrolment Hansen ML, Toft JC, et al. recommendations include use of continuous ECG was completed in April 2019. Trained GP nurses Heart 2021;107:635–641. (cECG) early after ischaemic stroke.8 conducted data collection in the primary sector and Lyckhage LF, et al. Heart 2021;107:635–641. doi:10.1136/heartjnl-2020-316904 635 Arrhythmias and sudden death research assistants or the primary investigator conducted data collection at the NVC. Heart: first published as 10.1136/heartjnl-2020-316904 on 3 July 2020. Downloaded from Study participants Participants included were AF- naive, had ischaemic stroke over 1 year before enrolment and were older than 49 at stroke onset. Participants with a systemic infection or taking antiarrhythmic drugs (class I and III, digoxin, flecainide, and non-dihydropyridine calcium-channel blockers), who had cECG within 1 year before inclusion, and who had an implanted loop recorder, cardioverter defibrillator or pacemaker were not eligible. Participants with an acute infection or surgery were included at least 1 month after remission. Participants taking OAC for other indications than AF were included. The ischaemic stroke diagnosis, established through review of patient records, was defined as evidence of previous focal central nervous system (CNS) infarction documented by clinical Figure 1 Flow chart of patient selection and distribution between findings and/or acute or chronic infarction, or a relevant perfu- study locations. *Class I and III, digoxin, flecainide, and non- sion defect on CT or MRI.9 Only imaging related to the last dihydropyridine calcium- channel blockers. GP clinic, general practice stroke diagnosis was evaluated. Where imaging lacked evidence clinic; ICD, implantable cardioverter defibrillator; TIA, transient ischaemic of infarction, we required neurological findings consistent with attack. upper motor neuron lesions, such as pathological reflexes, upper extremity pronation, central facial palsy or central ophthalmo- Baseline statistics of categorical variables were expressed as plegia, and no probable differential diagnosis. We also included counts and percentages. Normally and non- normally distributed participants with silent CNS infarction, detected during evalu- continuous variables were expressed as a median with limits of ation without certain stroke symptoms. Silent CNS infarctions IQR (Q1–Q3) and as mean and SD. The Clopper-P earson interval 10 are associated with increased risk of stroke. The subtype clas- method was used to determine percentages of AF (including sification of stroke was done in accordance with the Trial of Org 95% CI) as diagnosed by 12- lead ECG, 7-day Holter monitoring 11 10 172 in Acute Stroke Treatment. and for participants with irregular pulse determined during pulse palpation. Sensitivity, specificity, and positive and negative Cardiac rhythm evaluation predictive values including exact binomial confidence intervals Study evaluation for AF or atrial flutter included pulse palpa- were calculated by the epi. test function in the epiR package tion for irregular pulse, 12- lead ECG and 7-day cECG moni- in RStudio. Further, the OR of AF in high versus low levels of toring. All three evaluations were performed on all participants NT- proBNP was assessed by univariable logistic regression anal- http://heart.bmj.com/ and 12- lead ECG was performed minutes before or after appli- ysis and adjusted for age. Exploratory univariable analysis for cation of Holter equipment. Radial artery pulse palpation for AF risk by each covariable was conducted (online supplementary pulse irregularity was done for a minimum of 20 s or as long appendix methods and table S2). RStudio V.1.1.453 was used for as needed.12 The sensitivity and specificity of pulse palpation statistical analyses. were 0.92% and 0.82% in previous studies.13 A two- channel All participants gave an informed written consent.