Association between red blood cell distribution width and non-valvular atrial fibrillation in hemodialysis patients: a single-center Chinese population study.

BACKGROUND: Red blood cell distribution width (RDW) has emerged as a prognostic marker of atrial fibrillation (AF) in various clinical settings. However, the relationship by which RDW was linked to AF in hemodialysis (HD) patients was not clear. We sought to reveal the relationship between RDW and AF occurrence in HD patients. METHODS: We enrolled 170 consecutive maintenance HD patients, including 86 AF patients and 84 non-AF patients. All participants' medical history and detailed clinical workup were recorded before the first dialysis session of the week. Electrocardiography, laboratory and transthoracic echocardiography examination indices were compared between the AF group and non-AF group. Multivariable logistic regression analysis was performed to identify the independent predictors of AF occurrence in HD patients. RESULTS: There were all paroxysmal AF patients in AF group. Compared to the non-AF group, patients with AF group had a significantly older age (61.0 ± 1.48 vs. 49.71 ± 1.79, p < 0.001), lower BMI (24.3 ± 4.11 vs. 25.8 ± 3.87, p < 0.05), higher RDW (15.10 ± 0.96 vs. 14.26 ± 0.82, p < 0.001) and larger LAD (39.87 ± 3.66 vs. 37.68 ± 5.08, p < 0.05). Multivariable logistic regression analyses demonstrated that values of age (OR: 1.030, 95%CI: 1.004-1.057, per one- year increase), BMI (OR: 0.863, 95%CI: 0.782-0.952, per 1 kg/m2 increase), RDW (OR: 2.917, 95%CI: 1.805-4.715, per 1% increase) and LAD (OR: 1.097, 95%CI: 1.004-1.199, per 1 mm increase) were independently associated with AF occurrence (p < 0.05, respectively). The best cutoff value of RDW to predict AF occurrence was 14.65% with a sensitivity of 68.6% and a specificity of 72.6%. CONCLUSIONS: The increased RDW was significantly associated with the paroxysmal AF occurrence in HD patients.

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.

Empagliflozin, a sodium glucose co-transporter-2 inhibitor, alleviates atrial remodeling and improves mitochondrial function in high-fat diet/streptozotocin-induced diabetic rats.

BACKGROUND: Diabetes mellitus is an important risk factor for atrial fibrillation (AF) development. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are used for the treatment of type 2 diabetes mellitus (T2DM). Their cardioprotective effects have been reported but whether they prevent AF in T2DM patients are less well-explored. We tested the hypothesis that the SGLT-2 inhibitor, empagliflozin, can prevent atrial remodeling in a diabetic rat model. METHODS: High-fat diet and low-dose streptozotocin (STZ) treatment were used to induce T2DM. A total of 96 rats were randomized into the following four groups: (i) control (ii) T2DM, (iii) low-dose empagliflozin (10 mg/kg/day)/T2DM; and (iv) high-dose empagliflozin (30 mg/kg/day)/T2DM by the intragastric route for 8 weeks. RESULTS: Compared with the control group, left atrial diameter, interstitial fibrosis and the incidence of AF inducibility were significantly increased in the DM group. Moreover, atrial mitochondrial respiratory function, mitochondrial membrane potential, and mitochondrial biogenesis were impaired. Empagliflozin treatment significantly prevented the development of these abnormalities in DM rats, likely via the peroxisome proliferator-activated receptor-c coactivator 1α (PGC-1α)/nuclear respiratory factor-1 (NRF-1)/mitochondrial transcription factor A (Tfam) signaling pathway. CONCLUSIONS: Empagliflozin can ameliorate atrial structural and electrical remodeling as well as improve mitochondrial function and mitochondrial biogenesis in T2DM, hence may be potentially used in the prevention of T2DM-related atrial fibrillation.

Newly proposed electrocardiographic criteria for the diagnosis of left ventricular hypertrophy in a Chinese population.

BACKGROUND: The electrocardiographic criteria currently available for the diagnosis of left ventricular hypertrophy (LVH) are low in sensitivity. Thus, we compared the diagnostic performance of newly proposed electrocardiographic criteria to the existing criteria in a Chinese population. METHODS: A total of 235 consecutive hypertensive patients, hospitalized in our department between May 2017 and April 2018, were included. They were divided into two groups based on the gold standard echocardiogram: those with (n = 116) and without LVH (n = 119). The newly proposed ECG criteria were calculated by summating the amplitude of the deepest S wave (SD ) in any single lead and the S-wave amplitude of lead V4 (SV4 ). The area under the curve was calculated and compared against the sex-specific Cornell limb lead and Sokolow-Lyon criteria. RESULTS: ECG analysis of the cohort showed that the newly proposed criteria had the highest sensitivity in diagnosing LVH (male: 65.5%; female: 81%), followed by the Cornell limb lead criteria (male: 55.2%; female: 56.9%). The specificities of both sets of criteria were higher than 70%, with no significant differences between them. Receiver operator curve analysis showed an optimal cutoff of ≥2.1 mV for females (AUC: 0.832; 95% CI: 0.757-0.906) and ≥2.6 mV for males (AUC: 0.772; 95% CI: 0.687-0.856). CONCLUSION: The newly proposed SD  + SV4 criteria provide an improved sensitivity for the ECG diagnosis of LVH compared to existing criteria, but its routine use will require further validation in larger populations.

Red blood cell distribution width as a predictor of atrial fibrillation.

BACKGROUND: Current evidence suggests that a higher red blood cell distribution width (RDW) may be associated with increased risk of atrial fibrillation (AF) development. Given that some controversial results have been published, we conducted a systematic review of the current literature along with a comprehensive meta-analysis to evaluate the association between RDW and AF development. METHODS: We performed a systematic search of the literature using electronic databases (PubMed, Ovid, Embase, and Web of Science) to identify studies reporting on the association between RDW and AF development published until June 2016. We used both fix-effects and random-effects models to calculate the overall effect estimate. An I2  > 50% indicates at least moderate statistical heterogeneity. A sensitivity analysis and subgroup analysis were performed to find the origin of heterogeneity. RESULTS: A total of 12 studies involving 2721 participants were included in this meta-analysis. The standardized mean difference in the RDW levels between patients with and those without AF development was 0.66 units (P < .05; 95% confidence interval 0.44-0.88). A significant heterogeneity between the individual studies was observed (P < .05; I2  = 80.4%). A significant association between the baseline RDW levels and AF occurrence or recurrence following cardiac procedure or surgery was evident (SMD: 0.61; 95% confidence interval 0.33-0.88; P < .05) with significant heterogeneity across the studies (I2  = 80.7%; P < .01). CONCLUSIONS: Our comprehensive meta-analysis suggests that higher levels of RDW are associated with an increased risk of AF in different populations.

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.

Prognostic value of restless legs syndrome in hemodialysis patients: a systematic review and meta-analysis.

BACKGROUND: Previous studies have revealed that restless legs syndrome (RLS) not only is frequently prevalent in dialysis patients but also increases the risk of death in dialysis patients, especially in hemodialysis (HD) patients. However, inconsistent results also still exist, having attracted confusion and discussion. Owing to mixed and inconclusive results, we conducted to perform the comprehensive meta-analysis to evaluate the potential prognostic value of RLS in HD patients. MATERIALS AND METHODS: We conducted a systematic literature search using electronic databases (PubMed, Ovid, Embase and Web of Science) to identify relevant studies reporting on all-cause mortality and cardiovascular (CV) events in HD patients suffering from RLS. We searched the literature published up to December 5, 2016, or earlier. We used both fixed- and random-effects models to calculate the overall effect estimate. An I2>50% indicates at least moderate statistical heterogeneity. A sensitivity analysis and subgroup analysis were performed to find the origin of heterogeneity. RESULTS: A total of four studies including 1,839 patients found that there was no significant association between RLS and all-cause mortality (hazard ratio [HR]: 1.649; 95% confidence interval [CI]: 0.778-3.496) and CV events (HR: 0.863; 95% CI: 0.600-1.127) in HD patients. Heterogeneity among the studies was observed for all-cause mortality (I2=80.7%, P=0.001). CONCLUSION: Our meta-analysis suggests that there was no significant effect of RLS on all-cause mortality and CV events in HD patients. Therefore, large-scale and well-designed studies are needed to validate the association between RLS and the risk of death in HD patients.

Relation of red blood cell distribution width with CHADS2 and CHA2DS2-VASc score in Chinese patients with non-valvular atrial fibrillation.

BACKGROUND: Higher red cell distribution width (RDW) predicts adverse events in patients with cardiovascular diseases. However, there are limited data regarding the relationship between RDW and thromboembolism risk in the patients with atrial fibrillation (AF). We aimed to investigate the association between RDW and CHADS2, CHA2DS2-VASc scores used for the evaluation of thromboembolic risk in patients with non-valvular atrial fibrillation (AF). METHODS: Our study included 99 patients with AF (68 paroxysmal AF; 31 persistent AF). We calculated CHADS2 and CHA2DS2-VASc risk scores for each patient, and we carefully recorded clinical characteristics as well as laboratory and echocardiographic parameters. According to CHADS2 and CHA2DS2-VASc scores, we divided the AF patients into 2 groups (low-intermediate risk and high risk group). Subsequently, we compared the aforementioned parameters between the 2 groups, and we evaluated the relationship between RDW and CHADS2/CHA2DS2-VASc score. Finally, multivariate logistic regression analysis was performed to find independent predictors of high CHADS2, CHA2DS2-VASc scores. RESULTS: Patients with high CHADS2, CHA2DS2-VASc scores had older age, higher RDW, and creatinine levels, increased left atrial diameter and lower left ventricular ejection fraction, compared to the low CHADS2, CHA2DS2-VASc score group. Multivariate logistic regression analysis showed that RDW was an independent predictor for high CHADS2, CHA2DS2-VASc scores(OR: 2.184 and OR: 5.748; all P<0.05). CONCLUSION: RDW is significantly correlated with CHADS2 and CHA2DS2-VASc score in the patients with AF, while is an independent predictor for high CHADS2 and CHA2DS2-VASc score.

Association between air pollution and development of atrial fibrillation: A meta-analysis of observational studies.

BACKGROUND: Current evidence suggests that gaseous or particulate pollutants may increase the risk of atrial fibrillation (AF), although this association is still uncertain. METHODS: We conducted a systematic review of literature using PubMed, Ovid, Embase and Web of Science to identify studies reporting on the association between gaseous (ozone, carbon monoxide, sulfur dioxide, and nitrogen dioxide) or particulate matter 2.5 (PM2.5) and AF risk published until March 2015. The overall effect estimate was presented as the population-attributable risks with 95% CI. We used both fix-effects and random effects models to calculate the overall effect estimate. RESULTS: We retrieved 4 studies, involving 461,441 participants. There was a statistically significant association between AF development and all gaseous pollutant as well as PM2.5 [NO: 1.19% (0.70-1.67%), CO: 0.60 (0.20-1.09), SO2: 0.90 (0.60-1.28), O3: 1.09 (0.20-1.86), PM2.5: 0.89 (0.20-1.57)]. CONCLUSIONS: Our comprehensive meta-analysis suggests that gaseous or particulate pollutants are associated with the increased risk of AF.

Mineralocorticoid receptor antagonists and atrial fibrillation: a meta-analysis.

AIMS: Aldosterone has been implicated in atrial remodelling representing a potential target for upstream therapies. Accumulating evidence suggests that mineralocorticoid receptor blockade may have favourable effects on atrial fibrillation (AF) development, although some controversial results have been published. We, therefore, conducted a meta-analysis of randomized clinical trials (RCTs) and observational studies in order to examine the protective role of mineralocorticoid receptor antagonists (MRAs) on AF. METHODS AND RESULTS: Of the 1337 initially identified records, 3 RCTs and 2 observational studies with 3640 patients were finally analysed. The pooled analysis of the included studies demonstrated that patients treated with MRAs have 31% lower risk of AF compared with controls [relative ratio (RR): 0.69; 95% confidence interval (CI): 0.58-0.83] without any heterogeneity across the studies (I(2) = 0%). This effect was consistent across RCTs (RR: 0.72; 95% CI: 0.55-0.94) and observational studies (RR: 0.67; 95% CI: 0.53-0.84) without heterogeneity. Also, MRAs reduce the risk of AF in both heart failure (HF) (RR: 0.63; 95% CI: 0.50-0.80) and after cardiac surgery (RR: 0.77; 95% CI: 0.61-0.98). Analysing the relative impact of eplerenone and spironolactone, we showed that only eplerenone significantly reduces AF burden (RR: 0.64; 95% CI: 0.44-0.90). CONCLUSION: Our meta-analysis suggests that MRAs may be effective in AF prevention especially in the HF setting. However, there are insufficient data for the widespread use of aldosterone antagonists solely for AF prevention. Larger RCTs with long-term follow-up in different clinical settings are needed to clarify the impact of MRAs on AF.

Serum levels of nicotinamide-adenine dinucleotide phosphate oxidase 4 are associated with non-valvular atrial fibrillation.

Recent evidence indicates that nicotinamide-adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species have a pivotal role in the development of atrial fibrillation (AF). The present study aimed to investigate the potential association between serum levels of NOX4, as well as inflammatory biomarkers and AF. In total, 108 patients with AF (71 with paroxysmal AF and 37 with persistent/permanent AF) and 68 patients without AF, as the controls, were enrolled. The demographic, clinical, laboratory, electrocardiographic and echocardiographic characteristics were carefully recorded. Serum levels of myeloperoxidase (MPO), high-sensitivity C-reactive protein (hs-CRP) and NOX4 were assessed. Left atrial diameter (LAD), left ventricular end-diastolic diameter and P-wave dispersion were significantly increased in patients with paroxysmal AF and persistent/permanent AF compared with the controls, while NOX4 levels were significantly higher in patients with paroxysmal AF and persistent/permanent AF compared to the controls (155.57±90 and 155.88±64.79 vs. 126.72±23.51 pg/ml, respectively, P<0.05). A significant correlation between serum NOX4 levels and hs-CRP, and between NOX4 levels and MPO was also evident (r=0.170; r=0.227, P<0.05, respectively). Multivariate analysis demonstrated that the baseline serum NOX4 level was independently associated with paroxysmal AF [odds ratio (OR)=1.014; 95% confidence interval (CI), 1.001-1.027; P<0.05] and with persistent/permanent AF (OR=1.022; 95% CI, 1.000-1.044; P<0.05). There appears to be an association between increased NOX4 levels and AF, suggesting NOX4 involvement in the pathophysiology of human AF. Further studies are required to elucidate its role in atrial remodeling and to examine its potential prognostic impact.

Meta-Analysis on Risk Stratification of Asymptomatic Individuals With the Brugada Phenotype.

The prognosis of asymptomatic subjects remains the most controversial issue in Brugada syndrome (BS). A meta-analysis on the prognostic role of spontaneous type 1 electrocardiographic (ECG) pattern and programmed ventricular stimulation (PVS) in asymptomatic subjects with Brugada electrocardiogram was performed. Current databases were searched until March 2014. Fourteen prospective observational studies were included in the present meta-analysis, accumulating data on 3,536 asymptomatic subjects (2,820 men) with BS phenotype. The mean follow-up period varied from 20 and 77 months. Data regarding 1,398 asymptomatic subjects with spontaneous type 1 ECG pattern of BS were retrieved from 6 studies. During follow-up, arrhythmic events (sustained ventricular tachycardia/fibrillation, appropriate device therapies, or arrhythmic death) occurred in 42 patients (3%). The meta-analysis of these studies demonstrated that asymptomatic subjects with spontaneous type 1 ECG pattern of BS exhibit an increased risk of future arrhythmic events (odds ratio = 3.56, 95% confidence interval 1.70 to 7.47, Z = 3.37, p = 0.0008); 1,104 asymptomatic subjects with BS ECG pattern from 12 studies underwent PVS and were available for analysis. During follow-up, arrhythmic events occurred in 36 subjects (3.3%). Inducible ventricular arrhythmias at PVS were predictive of future arrhythmic events (odds ratio = 3.51, 95% confidence interval 1.60 to 7.67, Z = 3.14, p = 0.002). In conclusion, this meta-analysis showed that asymptomatic subjects with either spontaneous diagnostic ECG pattern or inducible ventricular arrhythmias at PVS are at increased risk.

Usefulness of Neutrophil/Lymphocyte Ratio as a Predictor of Atrial Fibrillation: A Meta-analysis.

BACKGROUND AND AIMS: Current evidence suggests that a high neutrophil/lymphocyte ratio (NLR) may increase the risk of atrial fibrillation (AF), but this association is still uncertain. The aim of the comprehensive meta-analysis was to evaluate the potential association between NLR and the risk of AF. METHODS: We conducted a systematic literature search using electronic databases (PubMed, Ovid, Embase, Cochrane Database and Web of Science) to identify the studies reporting the association between NLR and risk of AF. We searched the literature published January 2015 or earlier. We used both fixed-effects and random-effects models to calculate the overall effect estimate. An I(2) > 50% indicates at least moderate statistical heterogeneity. A sensitivity analysis and subgroup analysis were performed to find the origin of heterogeneity. RESULTS: We retrieved 11 studies involving a total of 2,766 participants. The combined odds ratio (OR) of incident AF for baseline NLR level was 1.25 (95% confidence interval [CI] 1.16-1.35) with significant heterogeneity across studies (I(2) = 82.7%, p < 0.01) and for the post-NLR level (following CABG, RFCA and cardioversion) was 1.518 (95% CI 1.076-2.142) with significant heterogeneity across studies (I(2) = 93.7%, p = 0.017). We also showed an association between AF recurrence following CABG, RFCA and cardioversion and baseline NLR level (OR 1.517, 95% CI 1.108-2.079) with significant heterogeneity across studies (I(2) = 86.8%, p < 0.01). CONCLUSIONS: Our comprehensive meta-analysis suggests that the high level of NLR, whether baseline or postsurgery/procedure, is associated with the increased risk of AF recurrence/occurrence.