Temporal Association Between Episodes of Atrial Fibrillation and Risk of Ischemic Stroke

Abstract

IMPORTANCEUnderstanding the temporal association between atrial fibrillation (AF) and ischemic stroke informs our understanding of the AF-stroke mechanism and treatment of paroxysmal AF.OBJECTIVE To define the temporal association between episodes of AF and stroke in patients with cardiac implantable electronic devices (CIEDs). DESIGN, SETTING, AND PARTICIPANTSIn this case-crossover study, data from a large national electronic health record database were linked with a single-vendor database of heart rhythm records of patients with CIEDs capable of continuous heart rhythm monitoring. Patients with CIEDs who sustained an ischemic stroke who also had 120 days of continuous remote rhythm monitoring prestroke were included. Data were collected from January 2007 to March 2017, and data were analyzed from November 2019 to June 2020.EXPOSURE AF for 5.5 hours or more on any given day during days 1 to 30 vs days 91 to 120 prestroke. MAIN OUTCOMES AND MEASURESOdds ratio for stroke comparing AF during days 1 to 30 vs 91 to 120 prestroke. This analysis was planned prior to the study. RESULTSFrom 466 635 patients included in both the Optum electronic health record and CareLink databases, 891 patients with CIEDs and ischemic stroke with continuous monitoring in the 120 days prestroke were identified. Of 891 included patients, 575 (64.5%) were male, and the median (interquartile range) age was 76 (67-82) years. The vast majority of patients with stroke had either no AF meeting the threshold duration of 5.5 hours or more in both the case and control periods (682 of 891 [76.5%]) or AF of 5.5 hours or more in both periods (143 of 891 [16.0%]). For those not meeting the 5.5-hour AF threshold in either period, there was no or very little AF throughout the 120 days prestroke. A total of 66 patients had informative, discordant arrhythmic states, with 52 having AF of 5.5 hours or more in the case period vs 14 in the control period (odds ratio [OR], 3.71; 95% CI, 2.06-6.70). Stroke risk was increased most in days 1 to 5 following an AF episode (OR, 5.00; 95% CI, 2.62-9.55). AF greater than 23 hours on a given day was associated with the clearest increase in stroke risk (OR, 5.00; 95% CI, 2.08-12.01). CONCLUSIONS AND RELEVANCEIn this large cohort of patients with CIEDs and continuous rhythm monitoring prior to ischemic stroke, excess stroke risk above baseline was highest within 5 days of an episode of AF of 5.5 hours or more in duration and diminished rapidly thereafter. Our findings are consistent with the traditional view that AF is directly and transiently associated with ischemic stroke. These results provide support for trials of time-delimited anticoagulation for patients with infrequent multihour episodes of AF and rigorous, continuous rhythm monitoring.

Stroke and Thromboembolism in Patients with Heart Failure and Sinus Rhythm: A Matter of Risk Stratification?

“…A recent case-crossover study of 891 patients with ischemic stroke and intracardiac devices explored the temporal association between incidence of AF and risk of ischemic stroke. Heart rhythm 30 days pre-stroke (cases) were compared to those 91-120 days pre-stroke (controls) (31); 52 patients experienced AF episodes of 5.5 hours or more in the case period of 30 days in comparison to 14 patients in the control period -reflecting a 3.71-fold increased risk of stroke in weeks following multi-hour AF episodes (31) The risk of stroke was the highest within the first five days after an AF episode. (31).…”

“…31 The risk of stroke was highest within the first 5 days after an AF episode. 31 While this cohort was not specific to patients with HF and most patients did not meet the threshold of AF burden, these results suggest that remote monitoring for these variables could assist in risk stratification of patients ( Fig. 4 ).…”

The Potential and Limitations of Mobile Health and Insertable Cardiac Monitors in the Detection of Atrial Fibrillation in Cryptogenic Stroke Patients: Preliminary Results From the REMOTE Trial

“…On the other hand, there is no consensus on the threshold of AF episode durations that are clinically relevant, especially in stroke patients ( 30 ). However, a study performed by Singer et al confirmed the direct and transient association between AF and stroke while using an AF duration threshold of 5.5 h. Furthermore, they found that AF episodes with a duration of more than 23 h were associated with the most significant increased stroke risk ( 31 ). Therefore, two discrete mHealth spot-check recordings per day using a smartphone or smartwatch should be sufficient to detect clinically relevant AF episodes.…”

Association between implantable loop recorder use and secondary stroke prevention: a meta-analysis

“…Third, device-detected AF burden is associated with an increased risk of ischaemic stroke in patients with cardiac implanted electronic devices 15. A recent study suggested that excess stroke risk above baseline was highest within 5 days of an episode of AF of 5.5 hours or more in duration and diminished rapidly thereafter 16. It is possible that a substantial portion of ILR-detected AF may be a lower burden, shorter duration and carrying a relatively lower risk of stroke 14…”