Identification of genetic, electroanatomical and structural predictors of malignant ventricular arrhythmias in patients with Brugada syndrome

Brugada syndrome is a genetic disease of the heart caused by dysfunction of ion channels regulating the ion fluxes in cardiac cells and therefore their electrical activity. In these patients, although the heart appears normal even at accurate evaluation including electrocardiogram and echocardiography, and no symptoms are present, the disease may cause sudden cardiac death through the unpredictable occurrence of malignant ventricular arrhythmias. Brugada syndrome is an important cause of sudden cardiac death in young people including athletes, although arrhythmias appear not to be related to physical effort but may occur even during sleep. The diagnosis is based on the presence of a specific electrocardiographic pattern that can be transient and can be unmasked by the cardiologist through the administration of specific drugs. Unfortunately antiarrhythmic drugs are not able to prevent the occurrence of malignant arrhythmias and therapy is based on the implantation under the skin of a device called defibrillator that can recognize and interrupt the arrhythmia when it occurs. In the last years, despite the improvement of genetic knowledge of the disease, no progress has been obtained with regard to a better comprehension of the mechanisms underlying the occurrence of arrhythmias and therefore no improvement of prevention and therapeutic strategies has been obtained. With this project we intend to clarify the mechanisms leading from ion channels' gene mutations to malignant arrhythmias. In all the patients enrolled we will perform genetic analysis, in vitro study of ion channels function and mostly an accurate study of myocardial biopsies obtained from regions of the heart presenting an abnormal electrical function. All patients will receive an implantable defibrillator whenever indicated and will be followed-up for at least 2 years. We will analyze the outcome and will identify the risk factors indicating which patients are at a higher risk of sudden death and which patients can be reassured about their prognosis, thus providing indications for a more accurate prevention of sudden death in these young patients.