The Autonomic Coumel Triangle: A New Way to Define the Fascinating Relationship between Atrial Fibrillation and the Autonomic Nervous System

Abstract

Arrhythmogenic substrate, modulating factors, and triggering factors (the so-called Coumel’s triangle concept) play a primary role in atrial fibrillation (AF) pathophysiology. Several years have elapsed since Coumel and co-workers advanced the concept of the relevance of autonomic nervous system (ANS) influences on atrial cells’ electrophysiological characteristics. The ANS is not only associated with cardiac rhythm regulation but also exerts an important role in the triggering and maintenance of atrial fibrillation. This review aims to describe in detail the autonomic mechanisms involved in the pathophysiology of atrial fibrillation (AF), starting from the hypothesis of an “Autonomic Coumel Triangle” that stems from the condition of the fundamental role played by the ANS in all phases of the pathophysiology of AF. In this article, we provide updated information on the biomolecular mechanisms of the ANS role in Coumel’s triangle, with the molecular pathways of cardiac autonomic neurotransmission, both adrenergic and cholinergic, and the interplay between the ANS and cardiomyocytes’ action potential. The heterogeneity of the clinical spectrum of the ANS and AF, with the ANS playing a relevant role in situations that may promote the initiation and maintenance of AF, is highlighted. We also report on drug, biological, and gene therapy as well as interventional therapy. On the basis of the evidence reviewed, we propose that one should speak of an “Autonomic Coumel’s Triangle” instead of simply “Coumel’s Triangle”.

Atrial Flutter After Radiofrequency Ablation for Barrett’s Esophagus: A Case Report

“…Acid reflux increases vagal activity, causing local inflammation directly entering the esophageal wall. This stimulates the adjacent vagal nerves, creating an arrhythmogenic substrate for re-entry circuits and increasing susceptibility to AF [ 13 ].…”

Ablation of Paroxysmal Atrial Fibrillation: between Present and Future

“…Modulating factors like autonomic tone impact AF genesis [ 20 ]. Indeed, it alters the electrical properties of atrial myocytes and this translates into complex and not always predictable effects on triggers and substrates, thus affecting not only the temporal behavior of AF (paroxysmal vs persistent) but also the arrhythmic burden and heart rate, therefore impacting on patient quality of life and heart failure risk [ 20 , 21 ]. Given this deep influence of the autonomic nerve system on AF, a working group suggested a new and revised pathogenetic hypothesis called “autonomic Coumel’s triangle” instead of just the Coumel’s triangle concept [ 21 ].…”

Orthostatic Stress and Baroreflex Sensitivity: A Window into Autonomic Dysfunction in Lone Paroxysmal Atrial Fibrillation

“…The autonomic nervous system (ANS) plays a central role in the pathogenesis of AF and influences atrial electrophysiology and function [ 14 , 15 , 16 , 17 ]. Both vagal and sympathetic activations can alter the electrophysiological properties of the atrium, leading to AF episodes [ 18 , 19 , 20 ].…”