Autonomic Afferent Dysregulation in Atrial Fibrillation

Abstract

Objectives: This study sought to evaluate the role of cardiac afferent reflexes in atrial fibrillation (AF). Background: Efferent autonomic tone is not associated with atrial remodeling and AF persistence. However, the role of cardiac afferents is unknown. Methods: Individuals with nonpermanent AF (n ¼ 48) were prospectively studied (23 in the in-AF group and 25 in sinus rhythm [SR]) with 12 matched control subjects. We performed: 1) low-level lower body negative pressure (LBNP), which decreases cardiac volume, offloading predominantly cardiac afferent (volume-sensitive) low-pressure baroreceptors; 2) Valsalva reflex (predominantly arterial high-pressure baroreceptors); and 3) isometric handgrip reflex (both baroreceptors). We measured beat-to-beat mean arterial pressure (MAP) and heart rate (HR). LBNP elicits reflex vasoconstriction, estimated using venous occlusion plethysmography–derived forearm blood flow (f1/vascular resistance), maintaining MAP. To assess reversibility, we repeated LBNP (same day) after 1-hour low-level tragus stimulation (in n ¼ 5 in the in-AF group and n ¼ 10 in the in-SR group) and >6 weeks post-cardioversion (n ¼ 7). Results: The 3 groups were well matched for age (59 12 years, 83% male), body mass index, and risk factors (P ¼ NS). The in-AF group had higher left atrial volume (P < 0.001) and resting HR (P ¼ 0.01) but similar MAP (P ¼ 0.7). The normal LBNP vasoconstriction (-49 5%) maintaining MAP (control subjects) was attenuated in the in-SR group (-12 9%; P ¼ 0.005) and dysfunctional in the in-AF group (þ11 6%; P < 0.001), in which MAP decreased and HR was unchanged. Valsalva was normal throughout. Handgrip MAP response was lowest in the in-AF group (P ¼ 0.01). Interestingly, low-level tragus stimulation and cardioversion improved LBNP vasoconstriction (-48 15%; P ¼ 0.04; and -32 9%; P ¼ 0.02, respectively). Conclusions: Cardiac afferent (volume-sensitive) reflexes are abnormal in AF patients during SR and dysfunctional during AF. This could contribute to AF progression, thus explaining “AF begets AF.”