Atrial fibrillation (AF) is the most commonly treated tachyarrhythmia worldwide. AF raises the risk of stroke 3-to 5-fold {1}. Chronic anticoagulation although burdensome is effective at reducing the risk of stroke. The stroke risk conferred by paroxysmal AF (PAF) has not been well characterized but has been arguably said to be the same as chronic AF {2}. In about 25% of patients who have ischemic strokes, no etiologic factor is identified {3}. Subclinical atrial fibrillation is often suspected to be the cause of stroke in these patients {4}. However, the prevalence and prognostic value of subclinical atrial fibrillation has been difficult to assess. Identification of short episodes such subclinical AF, therefore may be important to permit early intervention. A comprehensive detection of PAF is facilitated by modern day pacemakers, implantable cardioverter-defibrillators (ICDs), and other implantable monitors. The incidental finding of AF events recorded by dual-chamber pacemakers and ICDs is extremely common and poses a clinical challenge because the relationship between device-detected atrial tachyarrhythmias and stroke is not understood. The thromboembolic event risk attributable to these device-detected episodes of PAF remains unknown. In particular, it is not known whether there is a critical value of daily AF burden that has prognostic significance.

Recently, Healey et al reported the results of a prospective, industry funded, study involving patients in whom a pacemaker or defibrillator had recently been implanted (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial [ASSERT]; ClinicalTrials.gov number, NCT00256152). {5}

Study Questions

This study had two purposes: to determine whether asymptomatic episodes of atrial fibrillation were associated with stroke in patients not known to have AF and to determine whether a programmable algorithm to maintain a paced atrium reduced the risk of atrial fibrillation.

This study enrolled 2580 patients, 65 years of age or older, with hypertension and no history of AF, in whom a pacemaker or defibrillator had recently been implanted (within last 8 weeks), in over 23 countries. The patients were monitored for 3 months to detect subclinical atrial tachyarrhythmias (defined as episodes of atrial rate >190 beats per minute for more than 6 minutes) and then followed for a mean of 2.5 years for the primary outcome of ischemic stroke or systemic embolism. At 3 months the patients with pacemakers were randomly assigned to receive or not to receive continuous atrial overdrive pacing.

Three months after enrolment, device detection algorithms had recorded subclinical atrial tachycardia in 10% (n=261) of patients. 11 of the 261 patients (4.2%) in whom subclinical atrial tachyarrhythmias had been detected before 3 months had an ischemic stroke or systemic embolism (a rate of 1.69% per year), as compared with 40 of the 2319 in whom subclinical atrial tachyarrhythmias had not been detected (1.7%, a rate of 0.69% per year) (hazard ratio, 2.49; 95% CI, 1.28 to 4.85; P=0.007)

The risk was virtually unchanged after adjustment for baseline risk factors for stroke (hazard ratio, 2.50; 95% CI, 1.28 to 4.89; P=0.008). Of the 51 patients with a stroke or systemic embolism, 11 had had subclinical atrial tachyarrhythmias detected by 3 months, and none had had clinical atrial fibrillation by 3 months. Clinical atrial fibrillation occurred in 41 of the 261 patients who had had subclinical atrial tachyarrhythmias before the 3-month visit (15.7%) and in 71 of the 2319 patients who had not had subclinical atrial tachyarrhythmias before the 3-month visit (3.1%) (hazard ratio, 5.56; 95% confidence interval [CI], 3.78 to 8.17; P<0.001). The population attributable risk of ischemic stroke or systemic embolism associated with subclinical atrial tachyarrhythmia was 13%. There was no association between subclinical atrial tachyarrhythmias and any of the other clinical outcomes which included MI, death due to vascular cause and hospitalisation for heart failure.

The relative risk of ischemic stroke or systemic embolism associated with subclinical atrial tachyarrhythmia was consistent across increasing levels of baseline risk of stroke, as assessed by the CHADS2 score.

The major findings of this study are:

1) There was a substantial incidence of subclinical atrial tachyarrhythmias in hypertensive patients with a PPM or ICD and no previous history of AF

2) Subclinical atrial tachyarrhythmias were independently associated with significant risk of ischemic stroke or systemic embolism irrespective of other risk factors for stroke and of the presence of clinical atrial fibrillation.

3) The subclinical atrial tachyarrhythmias often preceded the development of clinical atrial fibrillation

Comment​

This study highlights the point that asymptomatic/subclinical AF can be significantly prothrombotic and that device detected AF burden is a potential risk for future thromboembolic effects. These episodes could be initial warning of AF development and thromboembolic events especially in similar group of patients. Practically it might imply aggressive screening for AF in patients with cryptogenic stroke with some form of continuous monitoring and having a low threshold for anticoagulation.

1) Benjamin EJ, Levy D, Vaziri SM, DAgostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort: the Framingham Heart Study. JAMA. 1994;271:840844.

2) Hohnloser SH, Pajitnev D, Pogue J, Healey JS, Pfeffer MA, Yusuf S, Connolly SJ. Incidence of stroke in paroxysmal versus sustained atrial fibrillation in patients taking oral anticoagulation or combined antiplatelet therapy: an ACTIVE W Substudy. J Am Coll Cardiol. 2007; 50: 21562161.

3) Wolf PA, Dawber TR, Thomas HE Jr, Kannel WB Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham Study. Neurology 1978; 28:973-977

4) Liao J, Khalid Z, Scallan C, Morillo C, O'Donnell M Noninvasive cardiac monitoring for detection of paroxysmal atrial fibrillation or flutter after acute ischemic stroke: a systematic review. Stroke 2007; 38:2935-2940

5) Healey JS etal. Subclinical atrial fibrillation and the stroke risk. N Engl J Med Jan 2012; 366:120-129