Atrial Fibrillation In Rheumatic Heart Disease Research Articles

Altered Expression of Transfer-RNA-Derived Small RNAs in Human With Rheumatic Heart Disease.

Rheumatic heart disease (RHD) remains a severe public health problem in developing countries. Atrial fibrillation (AF) is a medical complication of RHD. Although the understanding of disease pathogenesis has advanced in recent years, the key questions need to be addressed. Transfer RNA–derived small RNAs (tsRNAs) are a novel type of short non-coding RNAs with potential regulatory functions in various physiological and pathological processes. The present study used tsRNAs sequencing to investigate the relationship between RHD and atrial fibrillation (AF). Three paired cardiac papillary muscles were taken from six rheumatic RHD patients with AF (3 cases) or without AF (3 cases) from January 2016 to January 2017 in Xiangya Hospital, Central South University. A total of 219 precisely matched tsRNAs were identified, and 77 tsRNAs (fold change > 2.0 and P < 0.05) were differently changed. Three tsRNAs (AS-tDR-001269, AS-tDR-001363, AS-tDR-006049) were randomly selected and confirmed by qRT-PCR. The results of qRT-PCR were consistent with tsRNAs sequencing, suggesting the tsRNAs sequencing was reliable. Subsequently, we predicted the target mRNAs of the three tsRNAs. Moreover, we verified the functions of tsRNAs targeting mRNAs in vitro. Finally, bioinformatics analysis indicated that the target genes were abundant in regulation of transcription, DNA binding, intracellular. Most of the genes were predicted to interplay with cytokine-cytokine receptor by KEGG analysis. Our findings uncover the pathological process of AF in RHD through tsRNAs sequencing. This research provides a new perspective for future research on elucidating the mechanism of AF in RHD and offers potential new candidates for the treatment and diagnosis.

Role of inflammation in initiation and maintenance of atrial fibrillation in rheumatic mitral stenosis - An analytical cross-sectional study.

BackgroundInflammation has been implicated in the initiation and perpetuation of non‐valvular atrial fibrillation (AF). However, there is a lack of similar data on AF in rheumatic heart disease (RHD). The objective of this study was to analyze the association of inflammation as measured by serum inflammatory biomarkers with AF in rheumatic mitral stenosis (Rh‐MS).MethodsA comparative cross‐sectional analytical study was conducted on 181 Rh‐MS patients in normal sinus rhythm (NSR; n = 69), subclinical transient AF (SCAF; detected by 24‐hours Holter monitoring; n = 30) and chronic AF (n = 82). Serum hs‐CRP, IL‐6, and sCD‐40L were assessed using ELISA immunoassay and compared in all groups of Rh‐MS with or without AF.ResultsWe found significantly higher serum hs‐CRP and sCD‐40L levels in the overall AF (Chronic AF + SCAF) group (hs‐CRP: 4.5 ± 3.4 vs 2.3 ± 2.9 mg/L, P < .01; sCD‐40L: 6.4 ± 4.8 vs 3.1 ± 3.4 ng/mL, P < .01) and chronic AF subgroup (hs‐CRP: 4.9 ± 3.4 vs 2.3 ± 2.9 mg/L, P < .01; sCD‐40L: 6.9 ± 5.1 vs 3.1 ± 3.4 ng/mL, P < .01) compared to patients with sinus rhythm. There was a statistically significant graded increase of serum IL‐6 level from the NSR to the SCAF (vs NSR: 6.8 ± 3.9 vs 4.0 ± 2.2 pg/mL, P = .03), and chronic AF subgroups (vs NSR: 9.3 ± 6.5 vs 4.0 ± 2.2 pg/mL, P < .01; vs SCAF: 9.3 ± 6.5 vs 6.8 ± 3.9, P = .05) of atrial fibrillation.ConclusionsElevated levels of serum hs‐CRP, IL‐6, and sCD‐40L were strongly associated with overall AF and also with SCAF and chronic AF in Rh‐MS patients indicating a potential role of inflammation in the pathophysiology of rheumatic AF.

Galectin-3 Induces Atrial Fibrosis by Activating the TGF-β1/Smad Pathway in Patients with Atrial Fibrillation

Background: Atrial fibrosis plays a critical role in the occurrence and maintenance of atrial fibrillation. The role of TGF-β1 in mediating atrial fibrosis is well documented. The β-galactoside-binding lectin galectin-3 (Gal-3) is mainly produced by macrophages in biological events such as inflammation and angiogenesis. Previous studies have shown that Gal-3 is associated with atrial fibrosis, but the relationship between TGF-β1 and Gal-3 in atrial fibrosis remains unclear. Objective: To determine whether Gal-3 induces atrial fibrosis and atrial fibrillation by activating the TGF-β1/Smad pathway and whether the expression of Gal-3 is mediated by TGF-β1, which can enable assessing the relationship between Gal-3 and TGF-β1 in atrial fibrosis. Methods: In this study, 30 patients’ right atrial appendages were collected and divided into 3 groups: congenital heart disease sinus rhythm group (n = 10, as a control group), rheumatic heart disease sinus rhythm group (n = 10), and rheumatic heart disease atrial fibrillation group (n = 10). Rat atrial fibroblasts were cultured in vitro, and recombinant Gal-3 and recombinant TGF-β1 proteins were added to the cell culture. The expression of Gal-3, TGF-β1, Smad2, and collagen I was detected by Western blotting and quantitative real-time PCR. Atrial tissues were stained with Masson’s trichrome stain to evaluate the extent of atrial fibrosis. The expression of Gal-3 and TGF-β1 was detected by immunohistochemical staining and immunofluorescence staining. Gal-3 and TGF-β1 interaction was demonstrated by immunoprecipitation. Results: The expression levels of Gal-3, TGF-β1, Smad2, and collagen I were elevated in the rheumatic heart disease atrial fibrillation group compared with the congenital heart disease sinus rhythm group and the rheumatic heart disease sinus rhythm group. In cultured atrial fibroblasts, there is a synergistic interaction between Gal-3 and TGF-β1. Gal-3 stimulated the TGF-β1/Smad pathway, and overexpression of TGF-β1 induced Gal-3 expression. Conclusions: Gal-3 and TGF-β1 interact with each other and stimulate the downstream TGF-β1/Smad pathway. This finding suggests that Gal-3 could be an important factor in TGF-β1-induced fibrosis in atrial fibrillation.

Meta-Analysis of the Incidence, Prevalence, and Correlates of Atrial Fibrillation in Rheumatic Heart Disease.

Objective:To estimate the incidence, prevalence, and correlates of atrial fibrillation (AF) in a global population with rheumatic heart disease (RHD).Methods:Bibliographic databases were searched to identify all published studies providing data on AF in patients with RHD. Random-effects meta-analysis method was used to pool estimates.Results:Eighty-three studies were included, reporting data from 75,637 participants with RHD in 42 countries. The global prevalence of AF in RHD was 32.8% (range: 4.3%–79.9%). It was higher in severe valvular disease (30.8% vs 20.7%, p = 0.009), in severe mitral valve disease compared to severe aortic disease (30.4% vs 6.3%, p = 0.038). The global cumulative incidence of AF in patients with RHD was 4.8%, 11.4%, 13.2%, and 30.8% at 1, 2, 5, and 10 years of follow-up, respectively. From comparison between patients with and without AF, AF was associated with increased age (mean difference [MD]: 9.5 years; 95% CI: 7.8–1.3), advanced heart failure (odds ratio [OR]: 4.4; 95% CI 2.1–9.3), tricuspid valve involvement (OR: 4.0; 95% CI: 3.0–5.3), history of thromboembolism (OR: 6.2; 95% CI: 3.4–11.4), highly sensitive C-reactive protein (MD: 5.5 mg/dL; 95% CI: 1.2–9.8), systolic pulmonary arterial pressure (MD: 3.6 mmHg; 95% CI: 0.8–6.3), right atrium pressure (MD: 1.5 mmHg; 95% CI: 1.0–2.0), and left atrium diameter (MD: 8.1 mm; 95% CI: 5.5–10.7).Conclusions:About one-third of patients with RHD have AF, with an incidence which almost triples every five years after diagnosis. Factors associated with AF include age, advanced heart failure, thromboembolism, and few cardiac hemodynamics parameters.

Decreased Cardiac Expression of Heat Shock Protein 27 is Associated with Atrial Fibrillation in Patients with Rheumatic Heart Disease.

The objective of this study was to compare the expression of heat shock proteins (HSPs) between rheumatic heart disease (RHD) patients with atrial fibrillation (AF) and RHD patients without AF, and its efficacy in predicting the occurrence of AF in RHD patients. Ninety-five patients were enrolled in our study, including 60 RHD patients with AF, and 35 RHD patients without AF. The baseline characteristics of the patients such as gender, age, AF duration, left atrial diameter and left ventricular ejection fraction were collected, and erythrocyte sedimentation rate and high-sensitivity C-reaction protein were measured from all patients. Tissue samples were obtained from the right atrial appendage during open-heart surgery and then detected using immunohistochemical methods and Western blot with HSP27, HSP60, HSP70 and HSP90 antibodies. Compared with RHD patients without AF, the density of HSP27 positive protein in RHD patients with AF was significantly lower. The density of HSP60, HSP70 or HSP90 antibodies did not indicate significant difference between the two groups. Use of the Western blot experiment showed consistent results with immunohistochemical staining. In RHD patients with AF, the expression level of HSP27 protein was negatively associated with AF duration and left atrial diameter. Left atrial enlargement and low expression of HSP27 were the independent predictors of AF. The decreased expression level of HSP27 is associated with AF in RHD patients. Atrial fibrillation; Heat shock protein; Rheumatic heart disease.