Autoantibodies for Cardiac Channels and Sudden Cardiac Death and its Relationship to Autoimmune Disorders

Abstract

Sudden cardiac death (SCD) is an unexpected death caused by heart dysfunction. Autoantibodies against cardiac proteins may be potentially involved in the occurrence and progression of cardiac disease and SCD. The first report on the role of autoantibodies in idiopathic dilated cardiomyopathy appeared in the 1980s. In recent years new studies on the effects of the presence of specific autoantibodies and their relationship to ventricular arrhythmias and SCD were published. The purpose of the current mini-review is to analyze the results of the research studies focused on the relationship between anti-cardiomyocyte autoantibodies and SCD with respect to autoimmune disorders. According to our analysis, more research is needed to understand the role of these autoantibodies against cardiac proteins in the SCD pathogenesis, and potentially employ this knowledge for improving prognosis of SCD.

Pro-Arrhythmic Signaling of Thyroid Hormones and Its Relevance in Subclinical Hyperthyroidism

“…Risk factors for AF, such as aging, obstructive sleep apnea, diabetes, hypertension, dyslipidemia, obesity, cancer, renal dysfunction, and thyroid diseases, which are all accompanied by deleterious oxidative stress, may act synergistically to cause AF [5,15,[39][40][41][42][43][44], whereby the noncoding microRNAs translate cellular stressors, such as reactive oxygen species, into AF pathogenesis [45]. Emerging evidence suggests a significant role of the altered atrial metabolism, phosphorylation of proteins, inflammatory and autoimmune channelopathies, and presence of autoantibodies to the M2-muscarinic and β 1-adrenergic receptors in the pathogenesis of AF [46][47][48][49][50][51][52][53][54]. Due to these mentioned chronic stressors implicated in electrical remodeling and poor risk factors control, the incidence of AF increases globally.…”

“…Specific QRS complex patterns, recognized due to hypertrophy, may potentially predict ventricular arrhythmias [94]. When structural abnormalities are not evident, autoimmune channelopathies have been established as a novel mechanism in cardiac arrhythmias [51][52][53][54]95,96]. In particular, proarrhythmic autoantibodies targeting calcium, potassium, or sodium channels and anti-desmosome antibodies in the heart have been identified.…”

“…Anti-β adrenergic and anti-muscarinic receptor antibodies affect the myocardial electrophysiological properties and have been reported to be the independent predictors of sudden cardiac death in patients with various heart diseases [104]. The dysregulating effects of the autoantibodies against the calcium and potassium ion channels can play the basis for autoimmune phenocopies of genetic cardiac channelopathies [53]. Autoimmune cardiac channelopathies have been suggested as a novel mechanism in the development of cardiac arrhythmias [52].…”

“…It is noteworthy that the interaction of β1-adrenergic receptor autoantibodies with the target receptor amplifies the L-type Ca 2+ current (I Ca ) and rapid delayed rectifier K + currents (I ks , I kr ), which result in a decreased APD and the increase in the membrane potential during the plateau phase [53]. Interaction of the M2 muscarinic receptor autoantibodies with the target receptor inhibits ICa and increases the outward acetylcholine-regulated potassium current (I K,Ach ), which results in a hyperpolarization and shortening of APD [85].…”