Role of Heat Shock Proteins in Atrial Fibrillation: From Molecular Mechanisms to Diagnostic and Therapeutic Opportunities

Heat shock proteins (HSPs) are endogenous protective proteins and biomarkers of cell stress response, of which examples are HSP70, HSP60, HSP90, and small HSPs (HSPB). HSPs protect cells and organs, especially the cardiovascular system, against harmful and cytotoxic conditions. More recent attention has focused on the roles of HSPs in the irreversible remodeling of atrial fibrillation (AF), which is the most common arrhythmia in clinical practice and a significant contributor to mortality. In this review, we investigated the relationship between HSPs and atrial remodeling mechanisms in AF. PubMed was searched for studies using the terms "Heat Shock Proteins" and "Atrial Fibrillation" and their relevant abbreviations up to 10 July 2022. The results showed that HSPs have cytoprotective roles in atrial cardiomyocytes during AF by promoting reverse electrical and structural remodeling. Heat shock response (HSR) exhaustion, followed by low levels of HSPs, causes proteostasis derailment in cardiomyocytes, which is the basis of AF. Furthermore, potential implications of HSPs in the management of AF are discussed in detail. HSPs represent reliable biomarkers for predicting and staging AF. HSP inducers may serve as novel therapeutic modalities in postoperative AF. HSP induction, either by geranylgeranylacetone (GGA) or by other compounds presently in development, may therefore be an interesting new approach for upstream therapy for AF, a strategy that aims to prevent AF whilst minimizing the ventricular proarrhythmic risks of traditional anti-arrhythmic agents

Role of Heat Shock Proteins in Atrial Fibrillation: From Molecular Mechanisms to Diagnostic and Therapeutic Opportunities

Heat shock proteins (HSPs) are endogenous protective proteins and biomarkers of cell stress response, of which examples are HSP70, HSP60, HSP90, and small HSPs (HSPB). HSPs protect cells and organs, especially the cardiovascular system, against harmful and cytotoxic conditions. More recent attention has focused on the roles of HSPs in the irreversible remodeling of atrial fibrillation (AF), which is the most common arrhythmia in clinical practice and a significant contributor to mortality. In this review, we investigated the relationship between HSPs and atrial remodeling mechanisms in AF. PubMed was searched for studies using the terms “Heat Shock Proteins” and “Atrial Fibrillation” and their relevant abbreviations up to 10 July 2022. The results showed that HSPs have cytoprotective roles in atrial cardiomyocytes during AF by promoting reverse electrical and structural remodeling. Heat shock response (HSR) exhaustion, followed by low levels of HSPs, causes proteostasis derailment in cardiomyocytes, which is the basis of AF. Furthermore, potential implications of HSPs in the management of AF are discussed in detail. HSPs represent reliable biomarkers for predicting and staging AF. HSP inducers may serve as novel therapeutic modalities in postoperative AF. HSP induction, either by geranylgeranylacetone (GGA) or by other compounds presently in development, may therefore be an interesting new approach for upstream therapy for AF, a strategy that aims to prevent AF whilst minimizing the ventricular proarrhythmic risks of traditional anti-arrhythmic agents

Meta-analysis of Fragmented QRS as an Electrocardiographic Predictor for Arrhythmic Events in Patients with Brugada Syndrome

Fragmented QRS (fQRS) is an electrocardiographic marker related to ventricular fibrillation (VF) and sudden cardiac death (SCD) in various clinical settings. Current data regarding the prognostic significance of fQRS in Brugada syndrome (BrS) are contradictory. This meta-analysis aimed to evaluate the presence of fQRS as a risk stratification tool in BrS. Electronic databases (PubMed, EMBASE, and Cochrane Library) were searched until May 2016. Eight observational studies accumulating data on 1,637 BrS patients (mean age: 47 ± 11 years) were included in this meta-analysis. The mean follow-up duration ranged from 21 to 96 months. fQRS was found to be an independent predictor of future arrhythmic events in BrS (RR:3.88, 95% CI 2.26 to 6.65, p < 0.00001) with moderate heterogeneity (I2 = 54%, P = 0.03). When analyzing VF as independent end-point, the RR for VF was 3.61, and its 95% CI was 2.11 to 6.18, p < 0.00001. This meta-analysis showed that BrS patients with fQRS are at high risk for future arrhythmic events. The presence of fQRS warrants prospective evaluation as valid arrhythmogenic risk marker in BrS