Aging is associated with an increasing burden of morbidity, especially for cardiovascular diseases (CVDs). General cardiovascular risk factors, ischemic heart diseases, heart failure, arrhythmias, and cardiomyopathies present a significant prevalence in older people, and are characterized by peculiar clinical manifestations that have distinct features compared with the same conditions in a younger population. Remarkably, the aging heart phenotype in both healthy individuals and patients with CVD reflects modifications at the cellular level. An improvement in the knowledge of the physiological and pathological molecular mechanisms underlying cardiac aging could improve clinical management of older patients and offer new therapeutic targets.

Brugada syndrome (BrS) is an inherited autosomal dominant genetic disorder responsible for sudden cardiac death from malignant ventricular arrhythmia. The term “channelopathy” is nowadays used to classify BrS as a purely electrical disease, mainly occurring secondarily to loss-of-function mutations in the α subunit of the cardiac sodium channel protein Nav1.5. In this setting, arrhythmic manifestations of the disease have been reported in the absence of any apparent structural heart disease or cardiomyopathy. Over the last few years, however, a consistent amount of evidence has grown in support of myocardial structural and functional abnormalities in patients with BrS. In detail, abnormal ventricular dimensions, either systolic or diastolic dysfunctions, regional wall motion abnormalities, myocardial fibrosis, and active inflammatory foci have been frequently described, pointing to alternative mechanisms of arrhythmogenesis which challenge the definition of channelopathy. The present review aims to depict the status of the art of concealed arrhythmogenic substrates in BrS, often resulting from an advanced and multimodal diagnostic workup, to foster future preclinical and clinical research in support of the cardiomyopathic nature of the disease.