Cellular Physiology and Clinical Manifestations of Fascicular Arrhythmias in Normal Hearts

Abstract

Fascicular ventricular arrhythmias represent a spectrum of ventricular tachycardias dependent on the specialized conduction system. Although they are more common in structurally abnormal hearts, there is an increasing body of literature describing their role in normal hearts. In this review, the authors present data from both basic and clinical research that explore the current understanding of idiopathic fascicular ventricular arrhythmias. Evaluation of the cellular electrophysiology of the Purkinje cells shows clear evidence of enhanced automaticity and triggered activity as potential mechanisms of arrhythmias. Perhaps more importantly, heterogeneity in conduction system velocity and refractoriness of the left ventricular conduction system in animal models are in line with clinical descriptions of re-entrant fascicular arrhythmias in humans. Further advances in our understanding of the conduction system will help bridge the current gap between basic science and clinical fascicular arrhythmias.

Flecainide in Ventricular Arrhythmias: From Old Myths to New Perspectives

“…In structurally normal hearts, fascicular VT is generally caused by reentry circuit [36]; ECG morphology changes according to the exit site of the circuit from the retrograde-conducting fascicle: RBBB appearance with a left axis deviation if fascicular VT exits from the left posterior fascicle (90%) (Figure 1); RBBB appearance with a right axis deviation if VT exits from the left anterior fascicle [36]. Simultaneous anterograde activation of the left anterior and posterior fascicles with slow retrograde conduction through a separate septal fascicle can lead to upper septal fascicular VT (<1%), with narrow QRS (QRS < 110 ms) and normal axis [36,37].…”

New Insights into the Development and Morphogenesis of the Cardiac Purkinje Fiber Network: Linking Architecture and Function

“…While these While these cells represent a tiny fraction of the ventricular volume (1-2%) [9], their pathogenic role is disproportionately high given that they are thought to cause ectopic activation that can lead to life-threatening ventricular arrhythmias in structurally normal hearts and particularly in patients with cardiac disease [10]. In ventricular arrhythmia, Purkinje cells generate both automatic and triggered focal rhythms, while the architecture of the PF network favors re-entrant circuits, sustaining ventricular tachycardia and fibrillation [11,12]. [1].…”

Feasibility of selective cardiac ventricular electroporation

“…Of particular clinical value would be a means to selectively target the cardiac Purkinje system which plays a pivotal role in the genesis and maintenance of multiple different ventricular arrhythmias in both the failing and healthy heart. [17][18][19][20][21][22][23][24][25][26][27] In an acute ex-vivo model, PEFs delivered to the ventricular myocardium was shown to be successful in targeting Purkinje tissue [28]. In this study, PEF consistently eradicated all Purkinje potentials at voltages between 750V and 2500V and the ventricular electrogram amplitude was only minimally reduced, but not clinically significant, by ablation; 0.6 mV ± 2.3 mV (p = 0.03).…”

“…Reversible electroporation can provide a means for delivery of a vector into the Purkinje cell/fiber or temporarily disruption of Purkinje conduction. We postulate that this opens opportunities for the development of the vaccines for arrhythmia management in the context of all Purkinjerelated arrhythmias [21,27,37]. Additionally this also provides a means for abrupt and temporary arrest of Purkinje conduction in the acute setting of recalcitrant arrhythmias such as VF storm.…”