Cellular basis for triggered ventricular arrhythmias that occur in the setting of compensated hypertrophy and heart failure: considerations for diagnosis and treatment

Abstract

Malignant ventricular tachyarrhythmias are common among patients with hypertrophy and heart failure, and these arrhythmias can initiate by triggered activity. Abnormal repolarization and disturbed calcium handling due to remodeling processes are common features of the hypertrophied and failing heart that conspire to facilitate triggering events. These changes have a different cellular origin in compensated hypertrophy as compared with failure, which underscores the complexity of mechanisms that predispose the remodeled heart to arrhythmias. This hampers the identification of the vulnerable patient and adequate antiarrhythmic pharmacotherapy. Beat-to-beat variability of repolarization has been proposed as an early (noninvasive) electrographic detection method of triggered activity. An increase of variability heralds an enhanced risk of arrhythmias, and controlling this repolarization parameter by pharmacological agents is antiarrhythmic. Different drugs (flunarizine, ranolazine, K201, calmodulin kinase blockers) that are able to prevent and/or suppress triggered arrhythmias by specific mechanisms of action will be discussed.