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BackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Early diagnosis of AF is crucial for preventing AF-related morbidity, mortality, and economic burden, yet the detection of the disease remains challenging. The 12-lead electrocardiogram (ECG) is the gold standard for the diagnosis of AF. Because of technological advances, ambulatory devices may serve as convenient screening tools for AF. ObjectiveThe objective of this review was to investigate the diagnostic accuracy of 2 relatively new technologies used in ambulatory devices, non-12-lead ECG and photoplethysmography (PPG), in detecting AF. We performed a meta-analysis to evaluate the diagnostic accuracy of non-12-lead ECG and PPG compared to the reference standard, 12-lead ECG. We also conducted a subgroup analysis to assess the impact of study design and participant recruitment on diagnostic accuracy. MethodsThis systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. MEDLINE and EMBASE were systematically searched for articles published from January 1, 2015 to January 23, 2021. A bivariate model was used to pool estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the summary receiver operating curve (SROC) as the main diagnostic measures. Study quality was evaluated using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. ResultsOur search resulted in 16 studies using either non-12-lead ECG or PPG for detecting AF, comprising 3217 participants and 7623 assessments. The pooled estimates of sensitivity, specificity, PLR, NLR, and diagnostic odds ratio for the detection of AF were 89.7% (95% CI 83.2%-93.9%), 95.7% (95% CI 92.0%-97.7%), 20.64 (95% CI 10.10-42.15), 0.11 (95% CI 0.06-0.19), and 224.75 (95% CI 70.10-720.56), respectively, for the automatic interpretation of non-12-lead ECG measurements and 94.7% (95% CI 93.3%-95.8%), 97.6% (95% CI 94.5%-99.0%), 35.51 (95% CI 18.19-69.31), 0.05 (95% CI 0.04-0.07), and 730.79 (95% CI 309.33-1726.49), respectively, for the automatic interpretation of PPG measurements. ConclusionsBoth non-12-lead ECG and PPG offered high diagnostic accuracies for AF. Detection employing automatic analysis techniques may serve as a useful preliminary screening tool before administering a gold standard test, which generally requires competent physician analyses. Subgroup analysis indicated variations of sensitivity and specificity between studies that recruited low-risk and high-risk populations, warranting future validity tests in the general population. Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews CRD42020179937; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=179937

CKD is an independent risk factor for cardiovascular disease (CVD). The accumulation of uremic toxins in CKD induces oxidative stress and endothelial dysfunction. MicroRNA-92a (miR-92a) is induced by oxidative stress in endothelial cells (ECs) and involved in angiogenesis and atherosclerosis. We investigated a role for oxidative stress-responsive miR-92a in CKD. Our study of patients at three clinical sites showed increased serum miR-92a level with decreased kidney function. In cultured ECs, human CKD serum or uremic toxins (such as indoxyl sulfate), compared with non-CKD serum, induced the levels of miR-92a and suppressed the expression of miR-92a targets, including key endothelial-protective molecules. The antioxidant N-acetylcysteine inhibited these vasculopathic properties. In rats, adenine-induced CKD associated with increased levels of miR-92a in aortas, serum, and CD144+ endothelial microparticles. Furthermore, CD144+ microparticles from human uremic serum contained more miR-92a than those from control serum. Additional analysis showed a positive correlation between serum levels of miR-92a and indoxyl sulfate in a cohort of patients with ESRD undergoing hemodialysis. Collectively, our findings suggest that the uremic toxins accumulated in CKD can upregulate miR-92a in ECs, which impairs EC function and predisposes patients to CVD.

BackgroundOxidative stress activates endothelial innate immunity and disrupts endothelial functions, including endothelial nitric oxide synthase-derived nitric oxide bioavailability. Here, we postulated that oxidative stress induces sterol regulatory element-binding protein 2 (SREBP2) and microRNA-92a (miR-92a), which in turn activate endothelial innate immune response, leading to dysfunctional endothelium.Methods and resultsUsing cultured endothelial cells challenged by diverse oxidative stresses, hypercholesterolemic zebrafish, and angiotensin II-infused or aged mice, we demonstrated that SREBP2 transactivation of microRNA-92a (miR-92a) is oxidative stress inducible. The SREBP2-induced miR-92a targets key molecules in endothelial homeostasis, including sirtuin 1, Krüppel-like factor 2, and Krüppel-like factor 4, leading to NOD-like receptor family pyrin domain-containing 3 inflammasome activation and endothelial nitric oxide synthase inhibition. In endothelial cell-specific SREBP2 transgenic mice, locked nucleic acid-modified antisense miR-92a attenuates inflammasome, improves vasodilation, and ameliorates angiotensin II-induced and aging-related atherogenesis. In patients with coronary artery disease, the level of circulating miR-92a is inversely correlated with endothelial cell-dependent, flow-mediated vasodilation and is positively correlated with serum level of interleukin-1β.ConclusionsOur findings suggest that SREBP2-miR-92a-inflammasome exacerbates endothelial dysfunction during oxidative stress. Identification of this mechanism may help in the diagnosis or treatment of disorders associated with oxidative stress, innate immune activation, and endothelial dysfunction.

Objective: Heart failure (HF) imposes a substantial burden and the prevalence of HF is high in patients with chronic kidney disease (CKD). HF results in multiple hospital admissions, but whether HF subtypes worsen long-term outcomes and renal function in patients with CKD remains inconclusive.Methods: The study comprised 10 904 patients with CKD aged ≥20 years who underwent echocardiography between 1 January 2011 and 31 December 2018. The patients were stratified into four groups: non-HF, HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and HF with preserved ejection fraction (HFpEF). The primary end points were all-cause mortality, major adverse cardiovascular events (MACEs) and adverse renal outcomes.Results: In inverse probability of treatment weighting-adjusted method, the risk of all-cause mortality and MACEs relative to the non-HF group was greatest in the HFrEF group (HR 3.18 (95% CI 2.57 to 3.93) and HR 3.83 (95% CI 3.20 to 4.59)), followed by the HFmrEF (HR 2.75 (95% CI 2.22 to 3.42) and HR 3.08 (95% CI 2.57 to 3.69)) and HFpEF (HR 1.85 (95% CI 1.59 to 2.15) and HR 2.43 (95% CI 2.16 to 2.73) groups. In addition, the HFrEF group had the greatest risks of end-stage renal disease (HR 2.58 (95% CI 1.94 to 3.44)) compared with other groups.Conclusions: HF is associated with subsequent worse clinical outcomes, which may be more pronounced in patients with HFrEF, followed by those with HFmrEF and those with HFpEF relative to non-HF group. [ABSTRACT FROM AUTHOR]