Insulin mitigates acute ischemia induced atrial fibrillation and sinoatrial node dysfunction ex vivo
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE279356 | GEO | 2024/11/14
REPOSITORIES: GEO
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Project description:Background: On-pump cardiac surgery triggers sterile inflammation and postoperative complications such as postoperative atrial fibrillation (POAF). Hematopoietic somatic mosaicism (HSM) is a recently identified risk factor for cardiovascular diseases and results in a shift toward a chronic proinflammatory monocyte transcriptome and phenotype. Objectives: The aim of this study was to assess the prevalence, characteristics, and impact of HSM on preoperative blood and myocardial myeloid cells as well as on outcomes after cardiac surgery. Methods: Blood DNA from 104 patients referred for surgical aortic valve replacement (AVR) was genotyped using the HemePACT panel (576 genes). Four screening methods were applied to assess HSM, and postoperative outcomes were explored. In-depth blood and myocardial leukocyte phenotyping was performed in selected patients using mass cytometry and preoperative and postoperative RNA sequencing analysis of classical monocytes. Results: The prevalence of HSM in the patient cohort ranged from 29%, when considering the conventional HSM panel (97 genes) with variant allelic frequencies ≥2%, to 60% when considering the full HemePACT panel and variant allelic frequencies ≥1%. Three of 4 explored HSM definitions were significantly associated with higher risk for POAF. On the basis of the most inclusive definition, HSM carriers exhibited a 3.5-fold higher risk for POAF (age-adjusted OR: 3.5; 95% CI: 1.52-8.03; P = 0.003) and an exaggerated inflammatory response following AVR. HSM carriers presented higher levels of activated CD64+CD14+CD16- circulating monocytes and inflammatory monocyte-derived macrophages in presurgery myocardium. Conclusions: HSM is frequent in candidates for AVR, is associated with an enrichment of proinflammatory cardiac monocyte-derived macrophages, and predisposes to a higher incidence of POAF. HSM assessment may be useful in the personalized management of patients in the perioperative period.
2023-03-15 | GSE190353 | GEO
Project description:Insulin mitigates acute ischemia induced atrial fibrillation and sinoatrial node dysfunction ex vivo
| PRJNA1172142 | ENA
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.
| 2312263 | ecrin-mdr-crc
Project description:Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and post-operative atrial fibrillation (POAF) is a major healthcare burden, contributing to an increased risk of stroke, kidney failure, heart attack and death. Genetic studies have identified associations with AF, but no molecular diagnostic exists to predict POAF based on pre-operative measurements. Such a tool would be of great value for perioperative planning to improve patient care and reduce healthcare costs. In this pilot study of epigenetic precision medicine in the perioperative period, we carried out bisulfite sequencing to measure DNA methylation status in blood collected from patients prior to cardiac surgery to identify biosignatures of POAF. Methods: We enrolled 221 patients undergoing cardiac surgery in this prospective observational study. DNA methylation measurements were obtained from blood samples drawn from awake patients prior to surgery. After controlling for clinical and methylation covariates, we analyzed DNA methylation loci in the discovery cohort of 110 patients for association with POAF. We also constructed predictive models for POAF using clinical and DNA methylation data. We subsequently performed targeted analyses of a separate cohort of 101 cardiac surgical patients to measure the methylation status solely of significant methylation loci in the discovery cohort. Results: A total of 47 patients in the discovery cohort (42.7%) and 43 patients in the validation cohort (42.6%) developed POAF. We identified 12 CpGs that were statistically significant in the discovery cohort after correcting for multiple hypothesis testing. Of these sites, 6 were amenable to targeted bisulfite sequencing and chr16:24640902 was statistically significant in the validation cohort. In addition, the methylation POAF prediction model had an AUC of 0.79 in the validation cohort. Conclusions: We have identified DNA methylation biomarkers that can predict future occurrence of POAF associated with cardiac surgery. This research demonstrates the use of precision medicine to develop models combining epigenomic and clinical data to predict disease.
2022-05-05 | GSE194154 | GEO
Project description:Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and post-operative atrial fibrillation (POAF) is a major healthcare burden, contributing to an increased risk of stroke, kidney failure, heart attack and death. Genetic studies have identified associations with AF, but no molecular diagnostic exists to predict POAF based on pre-operative measurements. Such a tool would be of great value for perioperative planning to improve patient care and reduce healthcare costs. In this pilot study of epigenetic precision medicine in the perioperative period, we carried out bisulfite sequencing to measure DNA methylation status in blood collected from patients prior to cardiac surgery to identify biosignatures of POAF. Methods: We enrolled 221 patients undergoing cardiac surgery in this prospective observational study. DNA methylation measurements were obtained from blood samples drawn from awake patients prior to surgery. After controlling for clinical and methylation covariates, we analyzed DNA methylation loci in the discovery cohort of 110 patients for association with POAF. We also constructed predictive models for POAF using clinical and DNA methylation data. We subsequently performed targeted analyses of a separate cohort of 101 cardiac surgical patients to measure the methylation status solely of significant methylation loci in the discovery cohort. Results: A total of 47 patients in the discovery cohort (42.7%) and 43 patients in the validation cohort (42.6%) developed POAF. We identified 12 CpGs that were statistically significant in the discovery cohort after correcting for multiple hypothesis testing. Of these sites, 6 were amenable to targeted bisulfite sequencing and chr16:24640902 was statistically significant in the validation cohort. In addition, the methylation POAF prediction model had an AUC of 0.79 in the validation cohort. Conclusions: We have identified DNA methylation biomarkers that can predict future occurrence of POAF associated with cardiac surgery. This research demonstrates the use of precision medicine to develop models combining epigenomic and clinical data to predict disease.
2022-05-05 | GSE194155 | GEO
Project description:To establish changes in cardiomyocyte transcription profiles brought about by atrial fibrillation, we collected left atrial appendage samples from minipig induced by DOCA or DOCA and JK07 and from vehicle samples. The transcriptional profile of mRNA in these samples will be measured with high throughput technology. Changes in transcriptional profiles can be correlated with the physiologic profile of atrial fibrillation acquired at the time of harverst.
2025-03-01 | GSE255166 | GEO
Project description:Introduction: Post-operative atrial fibrillation (POAF) is a frequent complication after cardiac surgery, but its pathophysiology remains incompletely understood. Considering that epicardial adipose tissue (EAT) is in close vicinity with the atrial myocardium, we hypothesized that a specific pre-operative EAT phenotype would be associated to POAF onset following surgery. Methods: Patients undergoing cardiac surgery prospectively enrolled in the POMI-AF cohort between February 2016 and June 2017 were studied. EAT samples were collected at the beginning of surgery. Whole-tissue gene expression patterns and the stromal and vascular fraction (SVF) cellular composition were explored. Patients were followed after surgery by continuous ECG to detect POAF onset. Results: Among the 60 patients included in the cohort, 15 POAF and 15 non-POAF patients were matched based on pre-operative characteristics. Gene set enrichment analysis of transcriptomic data from pre-operative EAT samples revealed 40 enriched biological processes in POAF vs non-POAF patients. Most of these processes were related to cellular immune response. Leukocytes (63±15% of total cells), and more specifically lymphocytes (56±13% of total CD45+ cells), represented the major cell subset in the preoperative EAT SVF, with no quantitative differences between POAF and SR patients (76 [52; 84]% vs 56 [50; 64]%, p=0.22). However, POAF patients presented a significantly higher cytotoxic CD8+/helper CD4+ T lymphocyte ratio than SR patients (respectively, 0.69[0.55; 1.19] vs 0.50 [0.31; 0.54], p=0.03) suggesting a cytotoxic shift prior to surgery. Conclusion: Epicardial fat from patients who develop POAF displays a specific pre-operative transcriptome signature characteristic of cellular immune response and cytotoxic lymphocyte enrichment.
2020-06-01 | GSE143924 | GEO
Project description:Left Atrial Cardiomyocyte Transcriptomic Analysis of Postoperative Atrial Fibrillation.
| PRJNA1113721 | ENA
Project description:Analysis for early diagnosis of atrial fibrillation by finding changes in miRNA in the urine of patients with atrial fibrillation
2021-12-16 | GSE190898 | GEO
Project description:Regional differential expression of atrial fibrillation risk genes in the left atrium and pulmonary veins is not well studied, but may yield insights into atrial fibrillation pathogenesis. We tested the hypothesis that there is significant regional differential expression in left atrium structures. RNAseq was performed in 25 regions within the pulmonary veins (n=12), left atrial body (n=10), and left atrial appendage (n=3) from a 75 year old male with hypertension and atrial fibrillation who died of a stroke. These data show that genes involved in atrial fibrillation pathogenesis have substantial regional expression heterogeneity, particularly when comparing the left atrial body, pulmonary veins and left atrial appendage.
2020-11-14 | GSE161450 | GEO