Is Atrial Fibrillation Associated with Silent Cerebral Emboli?
Abstract & Commentary
By Edward P. Gerstenfeld, MD
Professor of Medicine, Chief, Cardiac Electrophysiology, University of California, San Francisco
Dr. Gerstenfeld does research for Biosense Webster, Medtronic, and Rhythmia Medical. This article originally appeared in the January 2014 issue of Clinical Cardiology Alert.
Synopsis: In this study comparing the prevalence of silent cerebral ischemia (SCI) and cognitive performance in patients with paroxysmal and persistent atrial fibrillation (AF) and controls in sinus rhythm, the authors concluded that patients with AF had more SCI and worse cognitive function than matched controls in sinus rhythm.
Source: Gaita F, et al. Prevalence of silent cerebral ischemia in paroxysmal and persistent atrial fibrillation and correlation with cognitive function. J Am Coll Cardiol 2013;62:1990-1997.
It is well known that patients with paroxysmal or persistent atrial fibrillation (AF) and appropriate risk factors are at increased risk of embolic stroke. However, the question of whether patients with AF on anticoagulant therapy are at higher risk of asymptomatic thomboemboli and cognitive dysfunction is unknown. In this study, patients with paroxysmal and persistent atrial fibrillation were recruited, along with matched control patients in sinus rhythm, from a cardiology clinic. All patients underwent diffusion weighted magnetic resonance imaging (MRI) of the brain, which is the best method for detecting asymptomatic or silent cerebral ischemia (SCI). The presence and number of SCIs were compared among patients with paroxysmal AF, persistent AF, and control. There were 90 patients with paroxysmal AF, 90 with persistent AF, and 90 control patients recruited. The baseline characteristics showed that 70% of paroxysmal AF patients and 73% of persistent AF patients had a CHA2DS2-VASc score ≥ 1. In addition, 43% of paroxysmal AF patients and 88% of persistent AF patients were taking oral anticoagulants. On MRI, at least one region of SCI on MRI was found in 80 (89%) patients with paroxysmal AF, 88 (98%) with persistent AF, and 41 (46%) controls. MRI lesions were bilateral in 90% of patients, suggesting an embolic etiology. The number of areas of SCI per patient was significantly higher in persistent than in paroxysmal AF, and both were greater than controls (persistent = 41.1 ± 28.0; paroxysmal = 33.2 ± 22.8; control = 12.0 ± 26.7; P < 0.01). On multivariate analysis, including use of oral anticoagulants and the CHA2DS2-VASc score, the presence of AF was independently associated with SCI (odds ratio, 7.2; 95% confidence interval, 2.3-22.3; P -0.001). The authors concluded that patients with AF had more SCI and worse cognitive function than matched controls in sinus rhythm.
AF remains the most common supraventricular arrhythmia, responsible for more hospitalizations and outpatient visits than any other arrhythmia. Several large randomized studies, including AFFIRM,1 have not demonstrated any mortality benefit to maintenance of sinus rhythm. The incidence of asymptomatic thromboemboli has come to attention after several studies found asymptomatic thromboemboli after catheter ablation of AF, and in one study, this was associated with cognitive decline.2 However, another large, retrospective study found that patients who underwent catheter ablation and remained in sinus rhythm had a lower incidence of dementia than those remaining in AF.3 The current study raises further suspicion that AF may lead to silent embolic events in many patients, and that these events may lead to subtle cognitive decline. This study also finds that embolic rates are higher for persistent compared to paroxysmal AF patients, a finding that makes sense, but has not been shown in prior studies. Of course there are no prospective data to suggest that maintenance of sinus rhythm, through pharmacologic or interventional means, will reduce that risk. However, the implications are provocative.
There are several limitations to this study, including the relatively small sample size and retrospective nature of the study. The high incidence of asymptomatic embolic events in the control population (46%) is difficult to explain, and may suggest that the MRI is a bit too sensitive. However, the authors convincingly argue that the pattern seen on the majority of MRIs is highly suggestive of chronic thromboembolic disease. Finally, during the study period, most patients were anticoagulated with warfarin, where time in therapeutic range (TTR) is often only ~50% and lower TTR has been associated with dementia.4 Whether the results would be similar with patients on newer oral anticoagulants is unknown. Will there be a prospective study of the effect of rate vs rhythm control on asymptomatic thomboemboli? The ongoing CABANA study,5 which randomizes patients to catheter ablation vs medical therapy, will examine this in a substudy. However, we are currently limited by the absence of an effective means to maintain sinus rhythm 100% of the time in AF patients, particularly those with persistent AF. So stay tuned — the relationship of asymptomatic cerebral emboli and dementia may reopen the issue of whether maintenance of sinus rhythm should be the goal in patients with AF.
- Wyse DG, et al. N Engl J Med 2002;347:1825-1833.
- Medi C, et al. J Am Coll Cardiol 2013;62:531-539.
- Bunch TJ, et al. Heart Rhythm 2010;7:433-437.
- Flaker GC, et al. Circ Cardiovasc Qual Outcomes 2010; 3:277-283.
- https://www.cabanatrial.org. Accessed December 17, 2013.