Atrial fibrillation burden: a new outcome predictor and therapeutic target

Abstract

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is not a dichotomous disease trait. Technological innovations enable long-term rhythm monitoring in many patients and can estimate AF burden. These technologies are already used to detect and monitor AF. This review describes the relation between AF burden and outcomes and potential effects of AF burden reduction. A lower AF burden is associated with a lower risk of stroke and heart failure in patients with AF: stroke risk without anticoagulation is lower in patients with device-detected AF and a low AF burden (stroke rate 1%/year) than in patients with persistent and permanent AF (stroke rate 3%/year). Paroxysmal AF shows intermediate stroke rates (2%/year). Atrial fibrillation burden-reducing interventions can reduce cardiovascular outcomes in patients with AF: early rhythm control reduces cardiovascular events including stroke and heart failure in patients with recently diagnosed AF and cardiovascular conditions. In patients with heart failure and AF, early rhythm control and AF ablation, interventions that reduce AF burden, reduce mortality and heart failure events. Recent technological innovations allow to estimate AF burden in clinical care, creating opportunities and challenges. While evidence remains limited, the existing data already suggest that AF burden reduction could be a therapeutic goal. In addition to anticoagulation and treatment of cardiovascular conditions, AF burden reduction emerges as a therapeutic goal. Future research will define the AF burden that constitutes a relevant risk of stroke and heart failure. Technologies quantifying AF burden need careful validation to advance the field.

Keywords: Atrial fibrillation; Burden; Oral anticoagulation; Rhythm control; Stroke.

Graphical Abstract

Clinical classification of atrial fibrillation (AF) and quantitative classification of AF using AF burden and its interaction and influence on outcomes, precision therapy, and clinical trials and research.

Figure 1

The estimated risk of stroke associated with atrial fibrillation burden or atrial fibrillation pattern. *According to the data of the LOOP study with median atrial fibrillation burden of 0.13% (interquartile range 0.03–1.05). Atrial fibrillation burden was defined as cumulative duration of all atrial fibrillation episodes lasting >6 min from the first adjudicated atrial fibrillation episode onward, divided by total duration of monitoring

Figure 2

Overview of current randomized controlled trials and studies regarding the correlation of the longest or median device-detected atrial fibrillation and/or atrial fibrillation burden with stroke risk (annual rate). The studies on the right side of of the figure depicts a higher estimated atrial fibrillation burden. In most of the studies, the stroke rate is displayed without anticoagulation. In some studies, the rate of anticoagulation varies as explained below. The figure illustrates concepts and, therefore, is simplified. More details can be found in the cited studies. For the ROCKET-AF study, the warfarin and rivaroxaban group are shown. In the rivaroxaban group, 17.5% patients had paroxysmal atrial fibrillation and 81.1% persistent atrial fibrillation. In the warfarin group, 17.8% had paroxysmal atrial fibrillation and 80.8% persistent atrial fibrillation. For ARTESiA and NOAH-AFNET 6, the median of the longest device-detected atrial fibrillation is displayed. In ARTESiA, patients with device-detected atrial fibrillation > 24 h were excluded. For ARTESiA and NOAH-AFNET 6, ischaemic stroke rate is displayed without anticoagulation. For the Carelink+OPTUM study, the rate for stroke/systemic embolism is displayed for device-detected atrial fibrillation > 23.5 h in non-anticoagulated patients. For the TRENDS study, the atrial tachycardia/atrial fibrillation burden is defined as the longest total atrial tachycardia/atrial fibrillation duration on any given day during the prior 30-day window. The rate for stroke/transient ischaemic attack/systemic embolism for the highest device-detected atrial fibrillation duration of 5.5 h is displayed in the plot. In the overall population of the TRENDS study, 20.8% of patients were on warfarin. For the LOOP study, the atrial fibrillation burden is the cumulative duration of all atrial fibrillation episodes lasting 6 min from the first adjudicated atrial fibrillation episode onwards, divided by total duration of monitoring. The rate for ischaemic stroke/transient ischaemic attack/systemic embolism is displayed in the implantable loop recorder group. In the implantable loop recorder group, in 29.2% participants, oral anticoagulation was initiated. For the SOS study, the stroke rate for episodes > 23 h duration is displayed. In EAST-AFNET 4, the rate for stroke for usual care and early rhythm control is displayed. *Indirect estimate; according to Charitos et al., the approximate atrial fibrillation burden for paroxysmal atrial fibrillation is 5%–11% (usual care) and for persistent/permanent atrial fibrillation 70%–100%. AF, atrial fibrillation; AT, atrial tachycardia; DDAF, device-detected atrial fibrillation; ILR, implantable loop recorder; TIA, transient ischaemic attack