Brugada Syndrome: Different Experimental Models and the Role of Human Cardiomyocytes From Induced Pluripotent Stem Cells

Abstract

Brugada syndrome (BrS) is an inherited and rare cardiac arrhythmogenic disease associated with an increased risk of ventricular fibrillation and sudden cardiac death. Different genes have been linked to BrS. The majority of mutations are located in the SCN5A gene, and the typical abnormal ECG is an elevation of the ST segment in the right precordial leads V1 to V3. The pathophysiological mechanisms of BrS were studied in different models, including animal models, heterologous expression systems, and human‐induced pluripotent stem cell–derived cardiomyocyte models. Currently, only a few BrS studies have used human‐induced pluripotent stem cell–derived cardiomyocytes, most of which have focused on genotype–phenotype correlations and drug screening. The combination of new technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 (CRISPR associated protein 9)‐mediated genome editing and 3‐dimensional engineered heart tissues, has provided novel insights into the pathophysiological mechanisms of the disease and could offer opportunities to improve the diagnosis and treatment of patients with BrS. This review aimed to compare different models of BrS for a better understanding of the roles of human‐induced pluripotent stem cell–derived cardiomyocytes in current BrS research and personalized medicine at a later stage.

Case report: Mechanical-electric feedback and atrial fibrillation–Revelation from the treatment of a rare atrial fibrillation caused by annular constrictive pericarditis

“…It may be caused by primary (idiopathic, tuberculosis, posterior viral or bacterial pericarditis, and connective tissue disease-related) or secondary factors (pericardial injury syndrome or radiation therapy) ( 10 , 11 ). AF was thought to be a part of the natural history of CP; however, it has been reported in only 20–30% of patients with CP ( 12 , 13 ), and more frequently in those with pericardial calcification ( 9 ). Pericardial thickening and/or calcification can be observed in patients with CP using echocardiographic or radiological imaging, although approximately 18% of patients were reported to have a normal pericardium ( 9 ).…”

“…AF was thought to be a part of the natural history of CP; however, it has been reported in only 20–30% of patients with CP ( 12 , 13 ), and more frequently in those with pericardial calcification ( 9 ). Pericardial thickening and/or calcification can be observed in patients with CP using echocardiographic or radiological imaging, although approximately 18% of patients were reported to have a normal pericardium ( 9 ). Annular CP (ACP), an extremely rare form of localized CP, is easily missed or misdiagnosed due to its unusual anatomical form.…”

“…The pathophysiological mechanisms responsible for initiating AF are complex and often vary among individuals (1,3,4). Predisposing factors, such as obesity, pericardial fat, obstructive sleep apnea, pre-hypertension, hyperthyroidism, excessive endurance exercise, cardiomyopathies, channelopathies, and heart failure (HF) play an important role in triggering the development of AF (1,2,(5)(6)(7)(8)(9). The regulation of these factors is essential for AF management, such as pharmacological control of HF, however, specific triggers may not be easily identifiable in clinical practice.…”

Novel insights in the pathomechanism of Brugada syndrome and fever‐related type 1 ECG changes in a preclinical study using human‐induced pluripotent stem cell‐derived cardiomyocytes

“…More than 50 gene mutations have been associated with BrS. 2 , 3 But nevertheless, 20%–30% of BrS cases are related to mutations or variants in the SCN5A gene (encoding the ion channel Na v 1.5). Among different variants in the SCN5A gene, the pathogenic role of each variant remains to be experimentally validated.…”

Incidence, recurrence and management of electrical storm in Brugada syndrome

“…Studies in animals and several cellular models have suggested a voltage gradient in the early phase of repolarization as a part of the ECG phenotype in BrS. A notched phase 1 of the right ventricular outflow tract myocardial action potential may explain a part of the pathomechanism of J-wave in BrS ( 11 ). This is related to a loss of function sodium channel current ( 12 ).…”