Brugada Syndrome: From Molecular Mechanisms and Genetics to Risk Stratification.

Brugada syndrome (BrS) is a rare hereditary arrhythmia disorder, with a distinctive ECG pattern, correlated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD) in young adults. BrS is a complex entity in terms of mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The main electrophysiological mechanism of BrS requires further research, with prevailing theories centered on aberrant repolarization, depolarization, and current-load match. Computational modelling, pre-clinical, and clinical research show that BrS molecular anomalies result in excitation wavelength (k) modifications, which eventually increase the risk of arrhythmia. Although a mutation in the SCN5A (Sodium Voltage-Gated Channel Alpha Subunit 5) gene was first reported almost two decades ago, BrS is still currently regarded as a Mendelian condition inherited in an autosomal dominant manner with incomplete penetrance, despite the recent developments in the field of genetics and the latest hypothesis of additional inheritance pathways proposing a more complex mode of inheritance. In spite of the extensive use of the next-generation sequencing (NGS) technique with high coverage, genetics remains unexplained in a number of clinically confirmed cases. Except for the SCN5A which encodes the cardiac sodium channel NaV1.5, susceptibility genes remain mostly unidentified. The predominance of cardiac transcription factor loci suggests that transcriptional regulation is essential to the Brugada syndrome's pathogenesis. It appears that BrS is a multifactorial disease, which is influenced by several loci, each of which is affected by the environment. The primary challenge in individuals with a BrS type 1 ECG is to identify those who are at risk for sudden death, researchers propose the use of a multiparametric clinical and instrumental strategy for risk stratification. The aim of this review is to summarize the latest findings addressing the genetic architecture of BrS and to provide novel perspectives into its molecular underpinnings and novel models of risk stratification.

Modern Approaches for the Treatment of Heart Failure: Recent Advances and Future Perspectives.

Heart failure (HF) is a progressively deteriorating medical condition that significantly reduces both the patients' life expectancy and quality of life. Even though real progress was made in the past decades in the discovery of novel pharmacological treatments for HF, the prevention of premature deaths has only been marginally alleviated. Despite the availability of a plethora of pharmaceutical approaches, proper management of HF is still challenging. Thus, a myriad of experimental and clinical studies focusing on the discovery of new and provocative underlying mechanisms of HF physiopathology pave the way for the development of novel HF therapeutic approaches. Furthermore, recent technological advances made possible the development of various interventional techniques and device-based approaches for the treatment of HF. Since many of these modern approaches interfere with various well-known pathological mechanisms in HF, they have a real ability to complement and or increase the efficiency of existing medications and thus improve the prognosis and survival rate of HF patients. Their promising and encouraging results reported to date compel the extension of heart failure treatment beyond the classical view. The aim of this review was to summarize modern approaches, new perspectives, and future directions for the treatment of HF.