Mechanisms of Arrhythmias in Ventricular Hypertrophy

Mechanisms of Arrhythmias in Ventricular Hypertrophy. Cardiac hypertrophy is an adaptative process by which the heart accommodates to abnormal pressure and volume overloads. However, hypertrophy of the left ventricle is associated with a high incidence of ventricular arrhythmias and sudden death. The cellular mechanisms responsible for the abnormal rhythmic activity in hypertrophied myocardium has not been clearly defined, but left ventricular hypertrophy is associated with characteristic electrical abnormalities in experimental models and in hypertrophied human tissue. The most consistent electrical alteration is prolonged duration of the action potential in hypertrophied myocardium. The prolonged duration of depolarization predisposes hypertrophied tissue to develop early afterdepolarizations, which can encourage the development of arrhythmias by a variety of mechanisms. Early afterdepolarizations interrupt repolarization and can lead directly to sustained triggered activity. Early afterdepolarizations can depolarize adjacent excitable fibers and thereby induce triggered activity. The prolonged duration of repolarization can enhance influx of calcium, which can in turn lead to delayed afterdepolarizations that can give rise to triggered activity. Early afterdepolarizations can also produce conduction block or delay, which could contribute to the development of reentrant arrhythmias. Early afterdepolarizations are the most likely electrical abnormality to arise from the prolonged time course of repolarization in hypertrophied myocardium. Therefore, therapeutic measures aimed at preventing the development of early afterdepolarizations in hypertrophied myocardium could prove to be a fruitful approach to inhibiting the development of arrhythmias. The development of agents that selectively reduce the duration of the action potential requires a better understanding of the ionic mechanisms responsible for prolonging the action potential in hypertrophied myocardium. In the meantime, avoiding factors known to favor the development of afterpotentials (e.g., extremes of heart rate, electrolyte abnormalities, certain antiarrhythmic drugs) in patients with left ventricular hypertrophy seems prudent.