scholarly journals Modulated Calcium Homeostasis and Release Events Under Atrial Fibrillation and Its Risk Factors: A Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Sarah Pei Ting Fong ◽  
Shaleka Agrawal ◽  
Mengqi Gong ◽  
Jichao Zhao

Background: Atrial fibrillation (AF) is associated with calcium (Ca2+) handling remodeling and increased spontaneous calcium release events (SCaEs). Nevertheless, its exact mechanism remains unclear, resulting in suboptimal primary and secondary preventative strategies.Methods: We searched the PubMed database for studies that investigated the relationship between SCaEs and AF and/or its risk factors. Meta-analysis was used to examine the Ca2+ mechanisms involved in the primary and secondary AF preventative groups.Results: We included a total of 74 studies, out of the identified 446 publications from inception (1982) until March 31, 2020. Forty-five were primary and 29 were secondary prevention studies for AF. The main Ca2+ release events, calcium transient (standardized mean difference (SMD) = 0.49; I2 = 35%; confidence interval (CI) = 0.33–0.66; p < 0.0001), and spark amplitude (SMD = 0.48; I2 = 0%; CI = −0.98–1.93; p = 0.054) were enhanced in the primary diseased group, while calcium transient frequency was increased in the secondary group. Calcium spark frequency was elevated in both the primary diseased and secondary AF groups. One of the key cardiac currents, the L-type calcium current (ICaL) was significantly downregulated in primary diseased (SMD = −1.07; I2 = 88%; CI = −1.94 to −0.20; p < 0.0001) and secondary AF groups (SMD = −1.28; I2 = 91%; CI = −2.04 to −0.52; p < 0.0001). Furthermore, the sodium–calcium exchanger (INCX) and NCX1 protein expression were significantly enhanced in the primary diseased group, while only NCX1 protein expression was shown to increase in the secondary AF studies. The phosphorylation of the ryanodine receptor at S2808 (pRyR-S2808) was significantly elevated in both the primary and secondary groups. It was increased in the primary diseased and proarrhythmic subgroups (SMD = 0.95; I2 = 64%; CI = 0.12–1.79; p = 0.074) and secondary AF group (SMD = 0.66; I2 = 63%; CI = 0.01–1.31; p < 0.0001). Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) expression was elevated in the primary diseased and proarrhythmic drug subgroups but substantially reduced in the secondary paroxysmal AF subgroup.Conclusions: Our study identified that ICaL is reduced in both the primary and secondary diseased groups. Furthermore, pRyR-S2808 and NCX1 protein expression are enhanced. The remodeling leads to elevated Ca2+ functional activities, such as increased frequencies or amplitude of Ca2+ spark and Ca2+ transient. The main difference identified between the primary and secondary diseased groups is SERCA expression, which is elevated in the primary diseased group and substantially reduced in the secondary paroxysmal AF subgroup. We believe our study will add new evidence to AF mechanisms and treatment targets.

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
C Verdicchio ◽  
A Elliott ◽  
R Mahajan ◽  
D Linz ◽  
D Lau ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction  Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia affecting 1-2% of the global population, with the prevalence of AF increasing dramatically over the past two decades. Although low levels of cardiorespiratory fitness (CRF) and physical activity are predictive of cardiovascular disease onset and mortality, only recently has this emerged as a potential risk factor for AF. Purpose The aim of this meta-analysis was therefore to quantify the relationship between CRF, measured by a symptom limited exercise stress test, and incident AF. We hypothesised that there would be an inverse relationship between CRF and the incidence of AF. Methods The systematic literature review was conducted using PUBMED, MEDLINE and EMBASE databases, with seven studies meeting the inclusion criteria. A random-effects meta-analysis was then used to compare the multivariate risk estimates of the lowest CRF group from each cohort with the group of the highest CRF. Results Data from 206,925 individuals (55.8% males) was used for analysis with a mean age of 55 ± 2.5 years and a mean follow-up period of 10.3 ± 5 years. The total number of AF events across the studies was 19,913. The overall pooled risk of AF in the high-CRF group versus the low-CRF group showed a significant lower risk of incident AF in those with high-CRF (OR: 0.52, 95% CI, 0.44-0.605, p < 0.001). There was evidence of statistical heterogeneity between the studies (I2 = 81%, p < 0.001). AF incidence rates demonstrated an overall decline in rates across the CRF quartiles from low to high. The mean incidence rate for low-CRF was 21 ± 13.4 compared to 6.9 ± 0.7 per 1000 person-years for the high CRF group (p = 0.03). Conclusion There is an inverse association between a lower CRF and an increased risk of AF, with a higher level of CRF protective against AF. This study highlights that low-CRF may be an additional risk factor for AF along with already other established lifestyle-based risk factors such as obesity and hypertension. Exercise interventions should be promoted as a primary prevention strategy in those at risk of developing AF with known risk factors. Future studies are warranted to identify the mechanism(s) through which improved CRF confers a reduction in AF incidence. Abstract Figure. AF risk between high and low-CRF


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Proietti ◽  
G.F Romiti ◽  
V Raparelli ◽  
I Diemberger ◽  
G Boriani ◽  
...  

Abstract Background Frailty is a clinical syndrome characterized by a reduced physiologic function, increased vulnerability to stressors, and an increased risk of adverse outcomes. Patients with Atrial Fibrillation (AF) are often burdened with a high number of comorbidities and prone to frailty. The prevalence of frailty, its management and association with major outcomes in patients with AF are still unclear. Purpose To estimate the pooled prevalence of frailty in patients with AF, as well as its association with AF-related risk factors and comorbidities, oral anticoagulants (OAC) prescription, and major outcomes. Methods We systematically searched PubMed and EMBASE, from inception to 31st January 2021, for studies reporting the prevalence of frailty (irrespective of the tool used for assessment). Pooled prevalence, odds ratio (OR), and 95% Confidence Intervals (CI) were computed using random-effect models; heterogeneity was assessed through the inconsistency index (I2). This study was registered in PROSPERO: CRD42021235854. Results A total of 1,116 studies were retrieved from the literature search, and 31 were finally included in the systematic review (n=842,521 patients). The frailty pooled prevalence was 39.6% (95% CI=29.2%-51.0%, I2=100%; Figure 1). Significant subgroup differences were observed according to geographical location (higher prevalence found in European-based cohorts; p=0.003) and type of tool used for the assessment (higher prevalence in studies using the Clinical Frailty Scale and Tilburg Frailty Index tools; p<0.001). Meta-regressions showed that study-level mean age and prevalence of hypertension, diabetes, and history of stroke were directly associated with frailty prevalence. Frailty was significantly associated with a 29% reduced probability of OAC prescription in observational studies (OR=0.71, 95% CI=0.62–0.81). Frail patients with AF were at higher risk of all-cause death (OR=4.12, 95% CI=3.15–5.41), ischemic stroke (OR=1.55, 95% CI=1.01–2.38), and bleeding (OR=1.55, 95% CI=1.12–2.14), compared to non-frail patients with AF. Conclusions In this systematic review and meta-analysis analysis, the prevalence of frailty was high in patients with AF, and associated with study-level mean age and prevalence of several stroke risk factors. Frailty may influence the management of patients, and worsening the prognosis for all major AF-related outcomes. FUNDunding Acknowledgement Type of funding sources: None. Prevalence of Frailty among AF patients


2020 ◽  
Vol 23 (4) ◽  
pp. E452-E460
Author(s):  
Jing Zhou ◽  
Zhefeng Kang ◽  
Lulu Liu ◽  
Yingqiang Guo ◽  
Sai Chen

Aims: Despite several clinical risk factors for atrial fibrillation (AF), some newly identified biomarkers may also potentially serve as risk factors for AF. However, none of these factors so far have been adopted in clinical practice. Recently, a number of studies with an attempt to identify the role of growth differentiation factor 15 (GDF-15) in AF have obtained ambiguous results. We try to identify the predicting role of GDF-15 in AF and AF-related complications with meta-analysis or systematic analysis. Methods and results: We enrolled 10 studies, looking at the predicting role of GDF-15 in non-valvular AF using meta-analysis, summarized its role in AF-related major complications, and discussed whether it was dependable to forecast postoperative AF. It turned out that GDF-15 is an independent factor to predict occurrence of AF, while it remains obscure to directly demonstrate its relationship with postoperative AF. For AF patients on anti-platelet treatment, GDF-15 plays a critical role in predicting major bleeding, cardiovascular death and overall death, and improves the current predicting model. Conclusions: Circulating GDF-15 greatly associates with AF and AF-related complications. It should be applied clinically.


2019 ◽  
Vol 106 (5) ◽  
pp. 534-547 ◽  
Author(s):  
D. Schizas ◽  
M. Kosmopoulos ◽  
S. Giannopoulos ◽  
S. Giannopoulos ◽  
D. G. Kokkinidis ◽  
...  

2018 ◽  
Vol 71 (11) ◽  
pp. A371
Author(s):  
Kennosuke Yamashita ◽  
Ravi Ranjan ◽  
Craig Selzman ◽  
Hu Nan ◽  
Derek J. Dosdall

2018 ◽  
Vol 67 (02) ◽  
pp. 107-116 ◽  
Author(s):  
Kennosuke Yamashita ◽  
Nan Hu ◽  
Ravi Ranjan ◽  
Craig Selzman ◽  
Derek Dosdall

Background Postoperative atrial fibrillation (POAF) is a common arrhythmia following cardiac surgery and is associated with increased health-care costs, complications, and mortality. The etiology of POAF is incompletely understood and its prediction remains suboptimal. Using data from published studies, we performed a systemic review and meta-analysis to identify preoperative clinical risk factors associated with patients at increased risk of POAF. Methods A systematic search of PubMed, MEDLINE, and EMBASE databases was performed. Results Twenty-four studies that reported univariate analysis results regarding POAF risk factors, published from 2001 to May 2017, were included in this meta-analysis with a total number of 36,834 subjects. Eighteen studies were performed in the United States and Europe and 16 studies were prospective cohort studies. The standardized mean difference (SMD) between POAF and non-POAF groups was significantly different (reported as [SMD: 95% confidence interval, CI]) for age (0.55: 0.47–0.63), left atrial diameter (0.45: 0.15–0.75), and left ventricular ejection fraction (0.30: 0.14–0.47). The pooled odds ratios (ORs) (reported as [OR: 95% CI]) demonstrated that heart failure (1.56: 1.31–1.96), chronic obstructive pulmonary disease (1.36: 1.13–1.64), hypertension (1.29: 1.12–1.48), and myocardial infarction (1.18: 1.05–1.34) were significant predictors of POAF incidence, while diabetes was marginally significant (1.06: 1.00–1.13). Conclusion The present analysis suggested that older age and history of heart failure were significant risk factors for POAF consistently whether the included studies were prospective or retrospective datasets.


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