Ethnic and racial differences in Asian populations with ion channelopathies associated with sudden cardiac death

Cardiovascular diseases are associated with several morbidities and are the most common cause of worldwide disease-related fatalities. Studies show that treatment and outcome-related differences for cardiovascular diseases disproportionately affect minorities in the United States. The emergence of ethnic and racial differences in sudden cardiac death (SCD) and related ion channelopathies complicates cardiovascular disease prevention, diagnosis, management, prognosis, and treatment objectives for patients and physicians alike. This review compiles and synthesizes current research in cardiac ion channelopathies and genetic disorders in Asian populations, an underrepresented population in cardiovascular literature. We first present a brief introduction to SCD, noting relevant observations and statistics from around the world, including Asian populations. We then examined existing differences between Asian and White populations in research, treatment, and outcomes related to cardiac ion channelopathies and SCD, showing progression in thought and research over time for each ion channelopathy. The review also identifies research that explored phenotypic abnormalities, device usage, and risk of death in Asian patients. We touch upon the unique genetic risk factors in Asian populations that lead to cardiac ion channelopathies and SCD while comparing them to White and Western populations, particularly in the United States, where Asians comprise approximately 7% of the total population. We also propose potential solutions such as improving early genetic screening, addressing barriers affecting access to medical care and device utilization, physician training, and patient education on risks

Pathophysiology of Cav1.3 L-type calcium channels in the heart

Ca2+ plays a crucial role in excitation-contraction coupling in cardiac myocytes. Dysfunctional Ca2+ regulation alters the force of contraction and causes cardiac arrhythmias. Ca2+ entry into cardiomyocytes is mediated mainly through L-type Ca2+ channels, leading to the subsequent Ca2+ release from the sarcoplasmic reticulum. L-type Ca2+ channels are composed of the conventional Cav1.2, ubiquitously expressed in all heart chambers, and the developmentally regulated Cav1.3, exclusively expressed in the atria, sinoatrial node, and atrioventricular node in the adult heart. As such, Cav1.3 is implicated in the pathogenesis of sinoatrial and atrioventricular node dysfunction as well as atrial fibrillation. More recently, Cav1.3 de novo expression was suggested in heart failure. Here, we review the functional role, expression levels, and regulation of Cav1.3 in the heart, including in the context of cardiac diseases. We believe that the elucidation of the functional and molecular pathways regulating Cav1.3 in the heart will assist in developing novel targeted therapeutic interventions for the aforementioned arrhythmias

Ion channel trafficking implications in heart failure

Heart failure (HF) is recognized as an epidemic in the contemporary world, impacting around 1%–2% of the adult population and affecting around 6 million Americans. HF remains a major cause of mortality, morbidity, and poor quality of life. Several therapies are used to treat HF and improve the survival of patients; however, despite these substantial improvements in treating HF, the incidence of HF is increasing rapidly, posing a significant burden to human health. The total cost of care for HF is USD 69.8 billion in 2023, warranting a better understanding of the mechanisms involved in HF. Among the most serious manifestations associated with HF is arrhythmia due to the electrophysiological changes within the cardiomyocyte. Among these electrophysiological changes, disruptions in sodium and potassium currents’ function and trafficking, as well as calcium handling, all of which impact arrhythmia in HF. The mechanisms responsible for the trafficking, anchoring, organization, and recycling of ion channels at the plasma membrane seem to be significant contributors to ion channels dysfunction in HF. Variants, microtubule alterations, or disturbances of anchoring proteins lead to ion channel trafficking defects and the alteration of the cardiomyocyte's electrophysiology. Understanding the mechanisms of ion channels trafficking could provide new therapeutic approaches for the treatment of HF. This review provides an overview of the recent advances in ion channel trafficking in HF

Autoimmune Calcium Channelopathies and Cardiac Electrical Abnormalities

Patients with autoimmune diseases are at increased risk for developing cardiovascular diseases, and abnormal electrocardiographic findings are common. Voltage-gated calcium channels play a major role in the cardiovascular system and regulate cardiac excitability and contractility. Particularly, by virtue of their localization and expression in the heart, calcium channels modulate pace making at the sinus node, conduction at the atrioventricular node and cardiac repolarization in the working myocardium. Consequently, emerging evidence suggests that calcium channels are targets to autoantibodies in autoimmune diseases. Autoimmune-associated cardiac calcium channelopathies have been recognized in both sinus node dysfunction atrioventricular block in patients positive for anti-Ro/La antibodies, and ventricular arrhythmias in patients with dilated cardiomyopathy. In this review, we discuss mechanisms of autoimmune-associated calcium channelopathies and their relationship with the development of cardiac electrical abnormalities