13th International Congress
THE "NEW FRONTIERS"
OF ARRHYTHMIAS 1998

January 24-31, 1998
Marilleva, Trento, Italy

S-64

The mechanisms of arrhythmogenesis

Michiel J. Janse.
Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Interuniversity Cardiology Institute, The Netherlands (ICIN), Utrecht, The Netherlands

Introduction

As a rule, an arrhythmia is not caused by a single mechanism. For most tachyarrhythmias, re-entry is the mechanism that sustains the rhythm disturbance, whilst the trigger is usually a premature depolarisation, often superimposed on a change in heart rate. Whereas virtually all known arrhythmogenic mechanism may give rise to a premature depolarisation¹, those that occur after an increase in heart rate are most likely caused by a delayed afterdepolarisation, those occurring after a long pause or during a period of bradycardia are most likely caused by an early afterdepolarisation. Arrhythmias may in principle be prevented both by abolishing the trigger or the substrate. For example, in post-infarction patients the substrate for re-entry is provided by the network of surviving myocardial fibres within the infarct², and in a substantial number of patients, ventricular tachycardia can be induced by programmed electrical stimulation, even when these arrhythmias do not occur spontaneously^3-5. It is likely that the success of beta-blocking treatment in preventing sudden death is due to suppressing the trigger, since beta-blockers with the greatest impact on preventing sudden death in post-infarction patients are those that produce the most marked slowing of sinus rhythm⁶. Still, the results of the CAST study⁷ where agents that were effective in suppressing ventricular premature beats, actually produced more lethal sustained arrhythmias, have shifted the emphasis towards therapeutic strategies aimed at destroying the substrate, i.e. by catheter ablation.

In the following description, abnormalities in impulse formation and conduction will be discussed separately even when they occur simultaneously. The three main categories of arrhythmia mechanisms: automaticity, triggered activity and re-entry, are schematically illustrated in figure 1.

Fig. 1: Schematic representation of the three main categories of mechanisms of arrhythmias. Top panel: automaticity, characterised by spontaneous diastolic (phase 4) depolarisation. Middle panel: triggered activity. The solid line indicates a transmembrane potential with both an early afterdepolarisation (during repolarisation) and a delayed afterdepolarisation (following complete repolarisation). The stippled line indicates trggered action potentials, emerging either from early of delayed afterdepolarisations. Lower panel: re-entry, characterised by unidirectional block in one pathway, slow conduction in one part of the circuit and re-excitation of the tissue proximal to the site of unidirectional block (reproduced with permission from Janse¹).