Pharmacological and device approach to therapy of inherited cardiac diseases associated with cardiac arrhythmias and sudden death

Abstract

A genetic origin in diseases like the long QT syndrome, the Brugada syndrome, or hypertrophic cardiomyopathy have been identified over the past years. These diseases have in common that they may result in sudden cardiac death of the patient. Recognition of patients based on their phenotype and application in clinical practice of the knowledge acquired on the genetic basis may have a major impact on how we approach them. In the long QT syndrome several mutations have been identified both in the sodium and in the potassium channels. The different electrophysiological effects of the mutations lead to a common phenotype: prolongation of the QT interval; but also to a common clinical impact: occurrence of malignant ventricular arrhythmias. Genetics should help us in treating in a more rational way our patients depending on the type of mutation. In the Brugada syndrome, mutations affecting the sodium channel have been so far identified. The results are electrophysiologically opposite to the ones observed in the long QT syndrome. Thus different mutations in the same gene lead to different functional consequences. Again, identification and study of the right mutation may lead to a more rational treatment directed to correct the malfunction of the channel.