3 research outputs found
The future of atrial fibrillation therapy: Intervention on heat shock proteins influencing electropathology is the next in line
Atrial fibrillation (AF) is the most common agerelated cardiac arrhythmia accounting for one-third of hospitalisations. Treatment of AF is difficult, which is rooted in the progressive nature of electrical and structural remodelling, called electropathology, which makes the atria more vulnerable for AF. Importantly, structural damage of the myocardium is already present when AF is diagnosed for the first time. Currently, no effective therapy is known that can resolve this damage. Previously, we observed that exhaustion of cardioprotective heat shock proteins (HSPs) contributes to structural damage in AF patients. Also, boosting of HSPs, by the heat shock factor-1 activator geranylgeranylacetone, halted AF initiation and progression in experimental cardiomyocyte and dog models for AF. However, it is still unclear whether induction of HSPs also prolongs the arrhythmia-free interval after, for example, cardioversion of AF. In this review, we discuss the role of HSPs in the pathophysiology of AF and give an outline of the HALT&REVERSE project, initiated by the HALT&REVERSE Consortium and the AF Innovation Platform. This project will elucidate whether HSPs (1) reverse cardiomyocyte electropathology and thereby halt AF initiation and progression and (2) represent novel biomarkers that predict the outcome of AF conversion and/or occurrence of post-surgery AF
Evaluating Serum Heat Shock Protein Levels as Novel Biomarkers for Atrial Fibrillation
Background: Staging of atrial fibrillation (AF) is essential to understanding disease
progression and the accompanied increase in therapy failure. Blood-based heat shock protein
(HSP) levels may enable staging of AF and the identification of patients with higher risk for AF
recurrence after treatment. Objective: This study evaluates the relationship between serum HSP
levels, presence of AF, AF stage and AF recurrence following electrocardioversion (ECV) or pulmonary
vein isolation (PVI). Methods: To determine HSP27, HSP70, cardiovascular (cv)HSP and HSP60
levels, serum samples were collected from control patients without AF and patients with paroxysmal
atrial fibrillation (PAF), persistent (PeAF) and longstanding persistent (LSPeAF) AF, presenting for
ECV or PVI, prior to intervention and at 3-, 6- and 12-months post-PVI. Results: The study population
(n = 297) consisted of 98 control and 199 AF patients admitted for ECV (n = 98) or PVI (n = 101).
HSP27, HSP70, cvHSP and HSP60 serum levels did not differ between patients without or with
PAF, PeAF or LSPeAF. Additionally, baseline HSP levels did not correlate with AF recurrence after
ECV or PVI. However, in AF patients with AF recurrence, HSP27 levels were significantly elevated
post-PVI relative to baseline, compared to patients without recurrence. Conclusions: No association
was observed between baseline HSP levels and the presence of AF, AF stage or AF recurrence.
However, HSP27 levels were increased in serum samples of patients with AF recurrence within one
year after PVI, suggesting that HSP27 levels may predict recurrence of AF after ablative therap
Cell-Free Circulating Mitochondrial DNA: A Potential Blood-Based Marker for Atrial Fibrillation
Atrial fibrillation (AF), the most common, progressive tachyarrhythmia is associated
with serious complications, such as stroke and heart failure. Early recognition of AF, essential to
prevent disease progression and therapy failure, is hampered by the lack of accurate diagnostic
serum biomarkers to identify the AF stage. As we previously showed mitochondrial dysfunction
to drive experimental and human AF, we evaluated whether cell-free circulating