Most forms of AVNRT are created by reentry between two

Most forms of AVNRT are created by reentry between two (or more) atrial connections to the AV node. The fast AV nodal pathway (shortest conduction time) is formed by transitional cells crossing the tendon of Todaro superiorly. Two slow AV nodal pathways are formed by the rightward and leftward inferior extensions of the AV node [68]. Atrial tissue surrounding Koch’s triangle is involved in all types of AVNRT. Optical mapping data obtained from isolated rabbit and adult mongrel dog AV nodal preparations suggested that AV nodal pathways are located outside the compact AV node, and atrial and transitional cells are involved in the reentrant circuit of AVNRT [69]. In light of these findings, we hypothesize that a loss of function of INa secondary to a mutation in sodium channel related genes (e.g., SCN5A, SCN1B, SCN10A) may cause reduced excitability, thus leading to block in one of the AV nodal pathways and the development of reentrant re-excitation. Action potential duration shortening in patients with SQTS leads to transmural dispersion of action potentials and subsequently spiral wave reentry resulting in AF [70]. Prolonged atrial trpv1 antagonist durations as demonstrated by monophasic action potentials in humans with LQTS can cause polymorphic AT potentially as a result of atrial early after depolarizations. These arrhythmias have been reported to be a specific arrhythmia of LQTS reminiscent of an atrial form of “torsades de pointes” [71]. The loss of CASQ2 causes abnormal sarcoplasmic reticulum Ca2+ release and selective interstitial fibrosis in the atrial pacemaker complex, which disrupts sinoatrial node pacemaking but enhances latent pacemaker activity, creates conduction abnormalities, and increases susceptibility to AF. These functional and extensive structural alterations could contribute to sinoatrial node dysfunction as well as AF in patients with CPVT [72].
Prognostic implications of atrial arrhythmias Several clinical and electrocardiographic/electrophysiological variables have been demonstrated to predict a worse outcome in patients with BrS, including aborted sudden death, presence of syncopal episodes in patients with a spontaneous type 1 Brugada pattern at baseline, fragmented QRS, and short (<200ms) ventricular effective refractory period [73,74]. Spontaneous AF in patients with BrS has been reported to be associated with syncope, documented ventricular fibrillation, aborted sudden death, and appropriate ICD shocks. This may represent a more advanced electrophysiological and structural remodeling in atrial as well as ventricular tissue [9,11]. Whether documentation of spontaneous AF in patients with BrS is an independent risk factor for a worse outcome remains unknown.
Management of atrial arrhythmias The management of atrial arrhythmias in the condition of BrS might be challenging for the following reasons. First, many anti-arrhythmic agents with sodium channel blocking properties might expose the patients to the development of ventricular arrhythmias [75,76], and second, patients with BrS might experience inappropriate ICD shocks because of atrial arrhythmias in approximately 5–10% of patients during an average 7-year follow-up period [18,77]. The use of AV node blocking agents (verapamil, diltiazem, and propranolol) for heart rate control and class IC anti-arrhythmic agents (propafenone and flecainide) in patients with paroxysmal and/or persistent AF is known to exacerbate the Brugada phenotype [75,76]. The safety of amiodarone and sotalol is currently unknown. Quinidine sulfate, a class IA anti-arrhythmic agent with strong vagolytic and Ito channel blocking properties is known to be a safe and effective treatment for patients with BrS and AF [14]. Pulmonary vein isolation (without any additional lesions) by radiofrequency energy or cyroablation can be performed safely and effectively in patients with BrS and drug-resistant AF with or without inappropriate ICD shocks [78,79]. Catheter ablation should be considered as a first choice of therapy for patients with AFL.