Project description:AimsCurrent guidelines recommend opportunistic screening for atrial fibrillation (AF) but the prognosis of individuals is unclear. The aim of this investigation is to determine prevalence and 1-year outcome of individuals with screen-detected AF.Methods and resultsWe performed a prospective, pharmacy-based single time point AF screening study in 7107 elderly citizens (≥65 years) using a hand-held, single-lead electrocardiogram (ECG) device. Prevalence of AF was assessed, and data on all-cause death and hospitalization for cardiovascular (CV) causes were collected over a median follow-up of 401 (372; 435) days. Mean age of participants was 74 ± 5.9 years, with 58% (N = 4130) of female sex. Automated heart rhythm analyses identified AF in 432 (6.1%) participants, with newly diagnosed AF in 3.6% of all subjects. During follow-up, 62 participants (0.9%) died and 390 (6.0%) were hospitalized for CV causes. Total mortality was 2.3% in participants with a screen-detected AF and 0.8% in subjects with a normal ECG [hazard ratio (HR) 2.94; 95% confidence interval (CI) 1.49-5.78; P = 0.002]; hospitalization for CV causes occurred in 10.6% and 5.5%, respectively (HR 2.08; 95% CI 1.52-2.84; P < 0.001). Compared with subjects without a history of AF at baseline and a normal ECG, participants with newly diagnosed or known AF had a significantly higher mortality risk with HRs of 2.64 (95% CI 1.05-6.66; P = 0.04) and 2.68 (95% CI 1.44-4.97; P = 0.002), respectively. After multivariable adjustment, screen-detected AF remained a significant predictor of death or hospitalization for CV causes.ConclusionPharmacy-based, automated AF screening in elderly citizens identified subjects with unknown AF and an excess mortality risk over the next year.
Project description:BackgroundAtrial fibrillation (AF) is the most common arrhythmia that is associated with high morbidity and mortality. The prevalence of AF increases with age and the elderly constitute a vulnerable cohort for higher stroke and bleeding complications.MethodsA total of 2163 adult consecutive patients with AF in 19 hospitals and 11 outpatient clinics in Jordan were enrolled in the Jordan AF study from May 2019 to January 2021. The clinical characteristics, demographics, and risk profiles of the elderly patients (≥80 years old) were compared to the younger patients (<80 years old).ResultsOf 2163 patients, 379 (17.5%) constituted the elderly group. The elderly group had higher prevalence of hypertension (79.9% vs 73.5%, p=0.01), lower prevalence of smoking (5.0% vs 15.2%, p<0.001) and lower body mass index (28.1 ± 5.5 kg/m2 vs 29.8 ± 6.2 kg/m2, p<0.001) compared with younger patients. They also had more strokes or systemic emboli (25.6% vs 14.7%, p<0.001), heart failure (30.3% vs 22.9%, p=0.002), pulmonary hypertension (30.6% vs 24.8%, p=0.02), and chronic kidney disease (13.5% vs 8.3%, p=0.002). The elderly cohort had higher mean CHA2DS2-VASc (5.0 ± 1.5 vs 3.6 ± 1.8, p<0.001) and HAS-BLED scores (2.2 ± 1.1 vs 1.5 ± 1.1, p<0.001) compared to younger group. Among 370 elderly with non-valvular AF (NVAF), oral anticoagulant agents (OACs) were prescribed for 278 (84.2%) of eligible high-risk patients. Of the 1402 younger patients with NVAF, OACs were prescribed for 1133 (84.3%) of eligible patients. Direct oral anticoagulant agents (DOACs) were more frequently used in the elderly compared to the young (72.3% vs 62.3%, p<0.001).ConclusionElderly Middle Eastern AF patients have worse baseline clinical profiles and higher risk scores compared to younger patients. The majority of the elderly were prescribed guideline directed OACs, with higher use of DOACs than the younger cohort.Clinical studies registrationThe study is registered on clinicaltrials.gov (unique identifier number NCT03917992).
Project description:The aim of this study is to perform transcriptome analysis on mouse left atrium tissue after long-term ibrutinib treatment or cardiac CSK knockout, in order to compared the enriched gene clusters.
Project description:This study will report the incidence of atrial fibrillation after elective colorectal cancer resection in the over 65 age group. This will be used to validate a risk model for the development of post-operative atrial fibrillation.
Eligible patients will undergo electrocardiogram based screening for atrial fibrillation, as well as brain natriuretic peptide tests prior to surgery. They will undergo 24 hour holter monitor prior to surgery, and at 30 and 90 days following surgery.
The primary outcome will be occurrence of atrial fibrillation within 90 days of surgery. Secondary outcomes include quality of life change, use of hospital services for atrial fibrillation, and complications of atrial fibrillation. This will be used to validate the pre-existing model for prediction of atrial fibrillation.
Project description:BackgroundMultimorbidity, polypharmacy and inappropriate prescribing is common in elderly patients worldwide. We aimed to explore the current status of multimorbidity, polypharmacy and the appropriateness of pharmacological therapy among elderly patients with atrial fibrillation (AF) in China.Materials and methodsWe randomly selected 500 patients aged 65 years or older from the China AF Registry study. Multimorbidity was defined as ≥2 comorbidities and polypharmacy was defined as ≥5 long-term prescribed drugs. Appropriateness of prescribing was evaluated using the Screening Tool of Older People's Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) criteria version 2. Patients' attitudes toward polypharmacy were evaluated by the Patients' Attitudes Towards Deprescribing (PATD) questionnaire.ResultsAmong the 500 patients included (mean age 75.2 ± 6.7 years, 49.0% male), 98.0% had multimorbidity and 49.4% had polypharmacy. The prevalence of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) was 43.6% (n = 218) and 71.6% (n = 358), respectively. Traditional Chinese medicine attributed largely to PIMs. Anticoagulants were the most common PPOs. Many clinical factors increased the risk of PIMs and PPOs. However, polypharmacy increased the risk of PIMs (OR 2.70, 95%CI 1.78-4.11; p < 0.0001), but not PPOs. In addition, 73.7% patients with polypharmacy were willing to have one or more of their medications prescribed if advised by their doctor.ConclusionMultimorbidity and polypharmacy were highly prevalent in elderly patients with AF in China. A high prevalence of inappropriate prescribing was also observed. Therefore, much more attention should be paid to the serious health problem in the elderly population.
Project description:BackgroundAtrial fibrillation (AF) and coronary artery disease (CAD) are closely related; CAD may precede or complicate the clinical course of AF.ObjectiveTo evaluate the impact of CAD on clinical outcomes among elderly Chinese AF patients.MethodsThe ChiOTEAF registry is a prospective registry conducted in 44 sites from 20 provinces in China between October 2014 and December 2018. Primary outcome was the composite of all-cause mortality/any thromboembolism (TE)/major bleeding/acute coronary syndrome (ACS).ResultsThe eligible cohort for this analysis included 6403 individuals (mean age 74.8 ± 10.7; 39.2% female); of these, 3058 (47.8%) had a history of CAD. On multivariate analysis, CAD was independently associated with a higher odds ratio for ACS (OR: 1.98; 95% CI: 1.12-3.52) without a significant impact on other adverse outcomes. Independent variables associated with the composite outcome among CAD patients were: (i) the use of OAC (OR: 0.55; 95% CI: 0.42-0.72), age (OR: 1.09; 95% CI: 1.08-1.11), heart failure (OR: 1.95; 95% CI: 1.51-2.50), prior ischemic stroke (OR: 1.29; 95% CI: 1.02-1.64), chronic kidney disease (OR: 1.71; 95% CI: 1.32-2.22), and chronic obstructive pulmonary disease (OR: 1.42; 95% CI: 1.06-1.89).ConclusionsAF patients with CAD were at an increased risk of developing ACS but there was no significant difference in the composite outcome, all cause death, cardiovascular death, thromboembolic events or major bleeding compared to the non-CAD group. OAC use was inversely associated with adverse events, yet their uptake was poor in the AF-CAD population.
Project description:AimsAdherence to guideline-directed oral anticoagulation (OAC) in patients with atrial fibrillation (AF) improves outcomes, but limited data are available from China. We evaluated the adherence to guideline-directed anticoagulation and its impact on clinical outcomes in a high-risk cohort of elderly Chinese patients.Methods and resultsThe Optimal Thromboprophylaxis in Elderly Chinese Patients with Atrial Fibrillation (ChiOTEAF) registry is a prospective, multicentre study conducted from October 2014 to December 2018. Endpoints of interest were all-cause death, thromboembolic (TE) events and major bleedings in patients with a guideline-directed indication for OACs (CHA2DS2-VASc ≥1 if male or ≥2 if female). The eligible cohort consisted of 5742 patients, of whom 2567 (44.7%) patients were treated with an OAC. Seven independent predictors of OAC undertreatment were identified: age [odds ratio (OR): 1.04; 95% confidence interval (CI): 1.03-1.05; P < 0.001], first diagnosed AF (OR: 1.71; 95%CI: 1.44-2.03; P < 0.001), chronic kidney disease (OR: 1.67; 95%CI: 1.36-2.06; P < 0.001), liver disease (OR: 1.69; 95%CI: 1.19-2.41; P = 0.003), dementia (OR: 1.67; 95%CI: 1.06-2.64; P = 0.026), prior extracranial bleeding (OR: 1.89; 95%CI: 1.35-2.64; P < 0.001), and the use of antiplatelet drug (OR: 6.97; 95%CI: 5.89-8.23; P < 0.001). On multivariate analysis, OAC undertreatment was significantly associated with a higher risk all-cause death (OR: 3.79; 95%CI: 2.61-5.53; P < 0.001) and TE events (OR: 2.28; 95%CI: 1.39-3.72; P = 0.001), and a similar risk of major bleeding as compared with guideline-directed OAC therapy.ConclusionOnly 44.7% of all eligible patients were prescribed OAC in accordance with guideline recommendations. The independent predictors for OAC undertreatment were age, first diagnosed AF, chronic kidney disease, chronic obstructive pulmonary disease, prior extracranial bleeding, and the use of the antiplatelet drugs. Guideline-adherent thromboprophylaxis was safe and may be associated with improved survival and less TE among elderly Chinese patients with AF.
Project description:Atrial fibrillation (AF) is a progressive arrhythmia for which current therapy is inadequate. During AF, rapid stimulation causes atrial remodeling that promotes further AF. The cellular signals that trigger this process remain poorly understood, however, and elucidation of these factors would likely identify new therapeutic targets. We have previously shown that immortalized mouse atrial (HL-1) myocytes subjected to 24 hr of rapid stimulation in culture undergo remodeling similar to that seen in animal models of atrial tachycardia (AT) and human AF. This preparation is devoid of confounding in vivo variables that can modulate gene expression (e.g., hemodynamics). Therefore, we investigated the transcriptional profile associated with early atrial cell remodeling. RNA was harvested from HL-1 cells cultured for 24 hr in the absence and presence of rapid stimulation and subjected to microarray analysis. Data were normalized using Robust Multichip Analysis (RMA), and genes exhibiting significant differential expression were identified using the Significance Analysis of Microarrays (SAM) method. Using this approach, 919 genes were identified that were significantly altered with rapid stimulation (763 up-regulated and 156 down-regulated). For many individual transcripts, changes typical of AF/AT were observed, with marked up-regulation of genes encoding BNP and ANP precursors, heat shock proteins, and MAP kinases, while novel signaling pathways and molecules were also identified. Both stress and survival response were evident, as well as up-regulation of multiple transcription factors. Genes were also functionally classified based on cellular component, biologic process, and molecular function using the Gene Ontology database to permit direct comparison of our data with other gene sets regulated in human AF and experimental AT. For broad categories of genes grouped by functional classification, there was striking conservation between rapidly stimulated HL-1 cells and AF/AT. Results were confirmed using real-time quantitative RT-PCR on 13 genes selected by physiological relevance in AF/AT and regulation in the microarray analysis (up, down, and nonregulated). Rapidly-stimulated atrial myocytes provide a complementary experimental paradigm to explore the initial cellular signals in AT remodeling to identify novel targets in the treatment of AF. Experiment Overall Design: HL-1 cell expression profile in vitro with and without rapid electric stimulation
Project description:Background Atrial fibrosis plays a critical role in the development of atrial fibrillation (AF). Exosome is a promising cell-free therapeutic approach for the treatment of AF. The purpose of this study was to explore the mechanisms underlying exosomes derived from atrial myocytes regulated atrial remodeling and ask whether their manipulation allows for therapeutic modulation of fibrosis potential abnormalities during AF. Methods We isolated exosomes from atrial myocytes and patients serum, microRNA (miRNA) sequencing analyzed the exosomal miRNAs in atrial myocytes-exosomes and patients serum-exosomes. mRNA sequencing and bioinformatics analysis corroborate the key gene as direct targets of miR-210-3p. Results The miRNAs sequencing analysis identified that miR-210-3p expression significantly increased in exosomes of tachypacing atrial myocytes and serum of AF patients. In vitro, the analysis showed that miR-210-3p inhibitor reversed tachypacing-induced proliferation and collagen synthesis in atrial fibroblasts. Accordingly, KO miR-210-3p could reduce the incidence of AF and ameliorate atrial fibrosis induced by Ang Ⅱ. The mRNA sequencing analysis and Dual-Luciferase reporter assay proved that glycerol-3-phosphate dehydrogenase 1-like (GPD1L) is the potential target gene of miR-210-3p. The functional analysis suggests that GPD1L regulated atrial fibrosis via PI3K/AKT signaling pathway. Besides, silencing GPD1L in atrial fibroblasts induced cells proliferation and these effects could be reversed by PI3K inhibitor (LY294002). Conclusion We demonstrate that atrial myocytes-derived exosomal miR-210-3p promoted the proliferation and collagen synthesis via inhibiting GPD1L in atrial fibroblasts. Preventing pathological crosstalk between atrial myocytes and fibroblasts may be as a novel target to improve atrial fibrosis in AF.