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28 Introduction Figure 8. Contemporary Summary of the Role of the ANS in AF AF Paroxysmal episodes time Permanent Autonomic Triggers Substrate- based AF-associated autonomic dysfunction Efferent autonomic cardiac innervation Contribution of AF-promoting risk factors ↑ Adrenergic nerve activity Autonomic Remodeling ↑ Cholinergic nerve activity 1. Automaticity 2. Early after depolarization 3. Delayed after depolarization (Ca 2+ overload/ryanodine-2 receptor dysfunction) Afferent autonomic cardiac innervation No structural changes ↑ Sympathetic nerve activity Sympathetic & parasympathetic hyper- innervation & Heterogeneity Electrical fractionation 1. Cardiopulmonary (low pressure) baroreceptor dysregulation 2. Arterial (high pressure) baroreceptors dysfunction Structural changes ↓ HRV associated with ↑ Incidence of AF Trigger- based (patchy) Questions to be addressed: Anatomic "AF Begets AF" LA dilatation Afferent volume- dysregula tion ?Link: Autonomic remodeling AF Paroxysmal episodes time Permanent Autonomic Triggers Substrate- based AF-associated autonomic dysfunction Efferent autonomic cardiac innervation Contribution of AF-promoting risk factors ↑ Adrenergic nerve activity Autonomic Remodeling ↑ Cholinergic nerve activity 1. Automaticity 2. Early after depolarization 3. Delayed after depolarization (Ca 2+ overload/ryanodine-2 receptor dysfunction) Afferent autonomic cardiac innervation No structural changes ↑ Sympathetic nerve activity Sympathetic & parasympathetic hyper- innervation & Heterogeneity Electrical fractionation 1. Cardiopulmonary (low pressure) baroreceptor dysregulation 2. Arterial (high pressure) baroreceptors dysfunction Structural changes ↓ HRV associated with ↑ Incidence of AF Trigger- based (patchy) Questions to be addressed: Anatomic "AF Begets AF" LA dilatation Afferent volume- dysregula tion ?Link: Autonomic remodeling Autonomic Triggers No structural changes Autonomic Remodeling Structural changes AF-Associated Autonomic Dysfunction Efferent autonomic cardiac innervation ↑ Adrenergic nerve activity ↑ Cholinergic nerve activity 1. Automaticity 2. Early afterdepolarization 3. Delayed afterdepolarization (Ca 2+ overload/ryanodine-2 receptor dysfunction) Sympathetic & parasympathetic hyper- innervation (Heterogeneity) AF Paroxysmal episodes time Permanent Autonomic Triggers Substrate- based AF-associated autonomic dysfunction Efferent autonomic cardiac innervation Contribution of AF-promoting risk factors ↑ Adrenergic nerve activity Autonomic Remodeling ↑ Cholinergic nerve activity 1. Automaticity 2. Early after depolarization 3. Delayed after depolarization (Ca 2+ overload/ryanodine-2 receptor dysfunction) Afferent autonomic cardiac innervation No structural changes ↑ Sympathetic nerve activity Sympathetic & parasympathetic hyper- innervation & Heterogeneity Electrical fractionation 1. Cardiopulmonary (low pressure) baroreceptor dysregulation 2. Arterial (high pressure) baroreceptors dysfunction Structural changes ↓ HRV associated with ↑ Incidence of AF Trigger- based (patchy) Questions to be addressed: Anatomic "AF Begets AF" LA dilatation Afferent volume- dysregula tion ?Link: Autonomic remodeling Electrical fractionation (patchy) Afferent autonomic cardiac innervation 1. Cardiopulmonary (low pressure) baroreceptor dysregulation 2. Arterial (high pressure) baroreceptor dysfunction Paroxysmal episodes Permanent Trigger- based Substrate- based ↑ Sympathetic nerve activity ↓ HRV associated with ↑ Incidence of AF Contribution of AF-prompting risk factors time "AF Begets AF" LA dilation Afferent volume dysregulation Autonomic remodeling Anatomic Questions to be addressed: Created by the Atrial Fibrillation Guideline Writing Committee. AF indicates atrial fibrillation; ANS, autonomic nervous system; HRV, heart rate variability; and LA, le atrium. 2.3.3. Role of the Autonomic Nervous System (ANS)

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