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The so-called Brugada syndrome (BS), first called precordial early repolarization syndrome (PERS), is characterized by the association of a fascinating electrocardiographic pattern, namely an aspect resembling right bundle branch block with a coved and sometime upsloping ST segment elevation in the precordial leads, and major ventricular arrhythmic events that could rarely lead to sudden death. Its electrogenesis has been related to a conduction delay mostly, but not only, located on the right ventricular outflow tract (RVOT), probably due to a progressive fibrosis of the conduction system. Many tests have been proposed to identify people at risk of sudden death and, among all, ajmaline challenge, thanks to its ability to enhance latent conduction defects, became so popular, even if its role is still controversial as it is neither specific nor sensitive enough to guide further invasive investigations and managements. Interestingly, a type 1 pattern has also been induced in many other cardiac diseases or systemic diseases with a cardiac involvement, such as long QT syndrome (LQTS), arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM) and myotonic dystrophy, without any clear arrhythmic risk profile. Evidence-based studies clearly showed that a positive ajmaline test does not provide any additional information on the risk stratification for major ventricular arrhythmic events on asymptomatic individuals with a non-diagnostic Brugada ECG pattern. [ABSTRACT FROM AUTHOR]

Over the past decades, there has been tremendous progress in understanding genetic alterations that can result in different phenotypes of human cardiomyopathies. More than a thousand mutations in various genes have been identified, indicating that distinct genetic alterations, or combinations of genetic alterations, can cause either hypertrophic (HCM), dilated (DCM), restrictive (RCM), or arrhythmogenic cardiomyopathies (ARVC). Translation of these results from "bench to bedside" can potentially group affected patients according to their molecular etiology and identify subclinical individuals at high risk for developing cardiomyopathy or patients with overt phenotypes at high risk for cardiac deterioration or sudden cardiac death. These advances provide not only mechanistic insights into the earliest manifestations of cardiomyopathy, but such efforts also hold the promise that mutation-specific pathophysiology might result in novel "personalized" therapeutic possibilities. Recently, the FLNC gene encoding the sarcomeric protein filamin C has gained special interest since FLNC mutations were found in several distinct and possibly overlapping cardiomyopathy phenotypes. Specifically, mutations in FLNC were initially only linked to myofibrillar myopathy (MFM), but are now increasingly found in various forms of human cardiomyopathy. FLNC thereby represents another example for the complex genetic and phenotypic continuum of these diseases. [ABSTRACT FROM AUTHOR]