Arrhythmogenic mechanisms in left ventricular hypertrophy

An important mechanism contributing to the high mortality and sudden death in patients with left ventricular hypertrophy (LVH) is ventricular arrhythmia. Part of the risk is associated with the pro-arrhythmic electrophysiological phenotype of the hypertrophied myocardium. The most consistently observed abnormality is prolongation of the action potential duration and refractoriness, which sets the stage for arrhythmias based on early or delayed afterdepolarizations and triggered activity. In addition, non-uniform prolongation of the action potential in LVH may be pro-arrhythmic by leading to increased dispersion of repolarization or refractoriness and favouring re-entry. The occurrence of delayed after depolarization-induced triggered activity and other ventricular arrhythmias are also related to the impaired ability to handle intracellular calcium due to changes in the density of ryanodine receptors and the Ca2+-ATPase of the sarcoplasmic reticulum. Slowing and fractionation of ventricular conduction, creating the conditions for micro-reentry and arrhythmogenesis, are characteristic of severe LVH, as is the expression of the I(f) current (which may be a source of increased automaticity). The pro-arrhythmic potential of LVH is also related to the presence of coexisting 'extrinsic' factors. The most important and pro-arrhythmic association of LVH is that with myocardial ischaemia. Other conditions include neuroendocrine factors, ventricular wall stress or electrolyte disturbances. The electrophysiological mechanisms of the interactions between these 'extrinsic' factors and LVH have not been fully elucidated. Further research into these mechanisms is required and may have important implications for our understanding of the mechanisms of cardiac arrhythmias in LVH and the appropriate use of antiarrhythmic drug therapy.