The role of the autonomous nervous system in atrial fibrillation progression. Data from the RACE V study
Authors: Van De Lande ME , Rajiv RS , Koldenhof T , Artola Arita V , Nguyen LBO , Weberndorfer V , Crijns HJGM , Elvan A , Hemels MEW , Tieleman RG , De Melis M , Schotten U , Linz D , Van Gelder IC , Rienstra M 
Published: May 2022

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): We acknowledge the support from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON 2014-9: Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling, and Vascular destabilisation in the progression of AF (RACE V). Unrestricted grant support from Medtronic Trading NL B.V.

Background
Atrial fibrillation (AF) progression is associated with adverse outcome.
The autonomic nervous system plays a yet unsettled role in initiation and progression of AF.

Purpose
To assess in patients with paroxysmal selfterminating AF differences in phenotype and AF progression depending on the role of the autonomic nervous system in triggering AF episodes.

Methods
Patients with paroxysmal AF included in the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study were analysed. Patients were extensively phenotyped at baseline and received continuous rhythm monitoring with an implantable loop recorder (ILR).To adequately define the role of the autonomic nervous system in triggering AF only patients with at least 3 selfterminating AF episodes were included. ILR data were used to assess whether AF was mainly vagally induced (&gt;80% of episodes starting during night time) or mainly adrenergically induced (&gt;80% starting during daytime), and to assess the development of AF progression. If a patient could not be identified as either vagal or adrenergic, they were classified as mixed AF. Primary outcome were differences in AF progression between the three groups. AF progression was defined as (1) progression to persistent or permanent AF, or (2) progression of PAF with &gt;3% burden increase. Follow-up was 2.2 (1.6-2.8) years.

Results
278 patients were included, median was age 66 (59-71) years, 117 (42%) were women (Table 1). Patients with vagally or adrenergically induced AF had less comorbidities compared to mixed AF patients (median 2 versus 2 versus 3, respectively, p=0.012). In the mixed group, compared to either the vagal or adrenergic group the estimated glomerular filtration rate was slightly worse (median 78 versus 84 versus 82 mL/min*1.73m2 in the mixed versus vagal and adrenergic group, respectively, p=0.018), diabetes was more common (12% versus 5% versus 0%, respectively, p=0.031). Obesity was most often present in the vagal group (38% versus 12% versus 27%, in the vagal versus adrenergic versus mixed group, respectively p=0.028). Progression rates in the vagal versus adrenergic versus mixed groups were 5% versus 5% versus 24%, respectively (p=0.013 vagal versus mixed and p=0.008 adrenergic versus mixed group, respectively)(Figure).

Conclusion
Important differences exist between AF patients depending on their autonomic nervous system associated triggering mechanisms. Patients with either vagally or adrenergically induced AF have less comorbidities as compared to those with a mixed initiation type of AF and showed lower AF progression rates.