The following are key points to remember from a review on how ablation to reduce atrial fibrillation (AF) burden may relate to clinical outcomes:

1. Consensus definitions classify paroxysmal AF as episodes lasting <7 days, persistent AF as episodes lasting >7 days, and long-standing persistent AF as continuous AF lasting >1 year in duration. Permanent AF represents AF in which the patient and clinician have decided to stop pursuing attempts to restore sinus rhythm. AF burden measurements can significantly overlap between clinical classifications and there is an increasing need to shift to the recognition of the burden of AF, which may correlate better to outcomes than mere recurrence of AF.
2. The 2019 American Heart Association/American College of Cardiology/Heart Rhythm Society AF guideline recommends oral anticoagulation to reduce stroke risk in AF patients based on an individual’s CHA₂DS₂-VASc score without consideration of AF type or pattern. This is supported by older studies that failed to show a significant difference in stroke risk when comparing patients with paroxysmal AF to patients with persistent or permanent AF. While the amount of AF or its pattern in patients with >1 risk factor for stroke may not alter the threshold for anticoagulation, the preponderance of evidence does suggest that longer durations of AF are associated with greater stroke risk. Studies have yet to show a consistent minimum threshold of AF burden that is associated with a significant increase in stroke.
3. There is a significant association between increasing daily AF burden and all-cause mortality, all-cause hospitalization, and cardiovascular hospitalization. Patients with high burden of subclinical AF had a significantly greater risk of the composite outcome of progression to clinical AF, ischemic stroke, myocardial infarction, heart failure (HF) hospitalization, and cardiac death than those with low or no subclinical AF.
4. Patients with both AF and heart failure with preserved (HFpEF) or reduced ejection fraction (HFrEF) suffer from greater morbidity and mortality than either condition alone. In patients with existing HF, greater AF burden is associated with a significantly increased risk of hospitalization due to HF and death.
5. Catheter ablation has been shown to delay progression from paroxysmal AF to persistent AF more effectively than antiarrhythmic therapy. Both ablation and medications have been shown to improve outcomes when instituted within 12 months of the initial AF diagnosis in the EAST-AFNET 4 trial. Patients randomized to early rhythm control in EAST-AFNET 4 had lower rates of stroke, hospitalization for worsening HF or acute coronary syndrome, and death from cardiovascular causes when compared to usual care.
6. Many trials have shown that catheter ablation is superior to medical therapy in freedom from AF and the quality of life. A prospective study of patients with symptomatic AF found that catheter ablation was associated with a significant improvement in quality of life regardless of ablative efficacy, defined as lack of recurrence of episodes of ≥30 seconds. These data support a shift towards primary outcomes that include AF burden and patient-reported symptoms to measure ablative success rather than the standard definition of recurrence.
7. Catheter ablation reduces health care utilization in patients with AF with significant reductions in the number of outpatient visits, inpatient admission days, and emergency room visits with catheter ablation compared to antiarrhythmic drug therapy in patients with AF. Several studies have demonstrated significantly reduced health care costs with ablation.
8. Data on the effect of catheter ablation on thromboembolic risk is mixed. Despite greater reduction in AF burden in patients treated with catheter ablation compared to medical therapy in the CABANA trial, there was no difference in the risk of stroke between the two groups. The EAST-AFNET 4 trial found lower stroke rates in those treated with early rhythm control. While EAST-AFNET 4 was not an ablation trial, it raised the hypothesis that earlier introduction of rhythm control (with either antiarrhythmic medications or ablation) may result in a lower risk of stroke in follow-up by reducing a patient’s AF burden.
9. Mortality benefit has not been demonstrated in the general population of AF patients who are treated with catheter ablation. The CABANA trial reported no significant difference in its primary endpoint (composite of death, disabling stroke, serious bleeding, or cardiac arrest) in symptomatic AF patients treated with ablation compared to patients treated with antiarrhythmic medical therapy. The CASTLE-AF trial compared catheter ablation to medical therapy for treatment of paroxysmal or persistent AF in patients with HFrEF. Treatment with catheter ablation was associated with a decrease in all-cause mortality and risk of hospitalization for worsening HF. These data suggest that AF burden after catheter ablation is an important outcome with greater clinical relevance than AF recurrence.  
10. As detection of AF improves with advancements in implanted and wearable cardiac monitoring devices, there are significant challenges determining the appropriate treatment of subclinical AF. Consensus is needed to establish the threshold of AF burden that warrants anticoagulation. Future research should investigate therapies that slow the progression of AF and prevent the negative outcomes associated with higher AF burden. In order to better assess the clinical success of ablation, recurrence should be defined as a burden of AF that is associated with lower quality of life, higher health care utilization, and higher risk of hospitalization or death.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure

Keywords: Anti-Arrhythmia Agents, Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Catheter Ablation, Heart Failure, Ischemic Stroke, Quality of Life, Risk Factors, Stroke, Stroke Volume, Thromboembolism, Wearable Electronic Devices

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