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Is endothelin gene polymorphism associated with postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting?

ABSTRACT: The mechanism of development of atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG) has not been clearly defined, and the involvement of multiple factors such as advanced age, withdrawal of β-blockers, inadequate atrial protection, and electrolyte imbalance, particularly hypomagnesemia has been documented by several authors. Despite all the available pharmacologic prophylaxis, incidence of AF still remains high in this group of patients. This unexplained cause could be genetic inheritance of endothelin-1 (ET-1) gene which is thought to have a pro-arrhythmogenic effect.This study aims to investigate the relationship between plasma ET-1 concentrations, ET-1 gene polymorphisms in loci -1370 T/G, -134 (3A/4A) Ins/del, Lys198Asn (G/T), and occurrence of AF in patients undergoing CABG.Ninety-eight nonrelated, nondiabetic patients over a period of 4 years undergoing routine CABG were selected for the present study. All patients were genotyped for three single nucleotide polymorphisms (SNPs) in loci -1370 T/G, -134 (3A/4A) Ins/del, and Lys198Asn (G/T) in the ET-1 gene by gene sequencing. The plasma ET-1 concentrations were measured using an ET immunoassay.Plasma ET-1 concentrations were higher in AF+ group (P = 0.001) as compared to AF- group. The allele frequencies between AF+ and AF- group were significantly different only with respect to the Lys198Asn (G/T) SNP of the ET-1 gene.The study described the possible correlation of polymorphism of ET gene in CABG population from India. The ET-1 gene might play a disease-modifying role in atrial fibrillation.

SUBMITTER: Dhawan I

PROVIDER: S-EPMC5535579 | biostudies-other | 2017 Jul-Sep

REPOSITORIES: biostudies-other

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Project description:Background The CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke or TIA [transient ischemic attack], vascular disease, age 65 to 74 years, sex category female; 2 indicates 2 points, otherwise 1 point) scoring system is recommended to guide decisions on oral anticoagulation therapy for stroke prevention in patients with nonsurgery atrial fibrillation. A score ≥1 in men and ≥2 in women, corresponding to an annual stroke risk exceeding 1%, warrants long-term oral anticoagulation provided the bleeding risk is acceptable. However, in patients with new-onset postoperative atrial fibrillation, the optimal risk stratification method is unknown. The aim of this study was therefore to evaluate the CHA2DS2-VASc scoring system for estimating the 1-year ischemic stroke risk in patients with new-onset postoperative atrial fibrillation after coronary artery bypass grafting. Methods and Results All patients with new-onset postoperative atrial fibrillation and without oral anticoagulation after first-time isolated coronary artery bypass grafting performed in Sweden during 2007 to 2017 were eligible for this registry-based observational cohort study. The 1-year ischemic stroke rate at each step of the CHA2DS2-VASc score was estimated using a Kaplan-Meier estimator. Of the 6368 patients included (mean age, 69.9 years; 81% men), >97% were treated with antiplatelet drugs. There were 147 ischemic strokes during the first year of follow-up. The ischemic stroke rate at 1 year was 0.3%, 0.7%, and 1.5% in patients with CHA2DS2-VASc scores of 1, 2, and 3, respectively, and ≥2.3% in patients with a score ≥4. A sensitivity analysis, with the inclusion of patients on anticoagulants, was performed and supported the primary results. Conclusions Patients with new-onset atrial fibrillation after coronary artery bypass grafting and a CHA2DS2-VASc score <3 have such a low 1-year risk for ischemic stroke that oral anticoagulation therapy should probably be avoided.

Project description:BackgroundPostoperative atrial fibrillation (POAF) is the most common cardiac dysrhythmia to occur after coronary artery bypass grafting (CABG). However, the risk factors for new-onset POAF after CABG during the perioperative period have yet to be clearly defined. Accordingly, the aim of our systematic review was to evaluate the perioperative predictors of new-onset POAF after isolated CABG.MethodOur review methods adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We searched seven electronic databases (PubMed, Embase, CINAHL, PsycArticles, Cochrane, Web of Science, and SCOPUS) to identify all relevant English articles published up to January 2020. Identified studies were screened independently by two researchers for selection, according to predefined criteria. The Newcastle-Ottawa Scale was used to evaluate the quality of studies retained.ResultsAfter screening, nine studies were retained for analysis, including 4798 patients, of whom 1555 (32.4%) experienced new-onset POAF after CABG. The incidence rate of new-onset POAF ranged between 17.3% and 47.4%. The following risk factors were identified: old age (p < 0.001), a high preoperative serum creatinine level (p = 0.001), a low preoperative hemoglobin level (p = 0.007), a low left ventricle ejection fraction in Asian patients (p = 0.001), essential hypertension (p < 0.001), chronic obstructive pulmonary disease (p = 0.010), renal failure (p = 0.009), cardiopulmonary bypass use (p = 0.002), perfusion time (p = 0.017), postoperative use of inotropes (p < 0.001), postoperative renal failure (p = 0.001), and re-operation (p = 0.005). All studies included in the analysis were of good quality.ConclusionsThe risk factors identified in our review could be used to improve monitoring of at-risk patients for early detection and treatment of new-onset POAF after CABG, reducing the risk of other complications and negative clinical outcomes.

Project description:Atrial tissue gene expression profiling may help to determine how differentially expressed genes in the human atrium before cardiopulmonary bypass (CPB) are related to subsequent biologic pathway activation patterns, and whether specific expression profiles are associated with an increased risk for postoperative atrial fibrillation (AF) or altered response to β-blocker (BB) therapy after coronary artery bypass grafting (CABG) surgery. Right atrial appendage (RAA) samples were collected from 45 patients who were receiving perioperative BB treatment, and underwent CABG surgery. The isolated RNA samples were used for microarray gene expression analysis, to identify probes that were expressed differently in patients with and without postoperative AF. Gene expression analysis was performed to identify probes that were expressed differently in patients with and without postoperative AF. Gene set enrichment analysis (GSEA) was performed to determine how sets of genes might be systematically altered in patients with postoperative AF. Of the 45 patients studied, genomic DNA from 42 patients was used for target sequencing of 66 candidate genes potentially associated with AF, and 2,144 single-nucleotide polymorphisms (SNPs) were identified. We then performed expression quantitative trait loci (eQTL) analysis to determine the correlation between SNPs identified in the genotyped patients, and RAA expression. Probes that met a false discovery rate<0.25 were selected for eQTL analysis. Of the 17,678 gene expression probes analyzed, 2 probes met our prespecified significance threshold of false discovery rate<0.25. The most significant probe corresponded to vesicular overexpressed in cancer - prosurvival protein 1 gene (VOPP1; 1.83 fold change; P=3.47×10(-7)), and was up-regulated in patients with postoperative AF, whereas the second most significant probe, which corresponded to the LOC389286 gene (0.49 fold change; P=1.54×10(-5)), was down-regulated in patients with postoperative AF. GSEA highlighted the role of VOPP1 in pathways with biologic relevance to myocardial homeostasis, and oxidative stress and redox modulation. Candidate gene eQTL showed a trans-acting association between variants of G protein-coupled receptor kinase 5 gene, previously linked to altered BB response, and high expression of VOPP1. In patients undergoing CABG surgery, RAA gene expression profiling, and pathway and eQTL analysis suggested that VOPP1 plays a novel etiological role in postoperative AF despite perioperative BB therapy.

Project description:BACKGROUND:Cardiac troponin T (cTnT) is elevated after coronary artery bypass grafting surgery. The aim of this study was to determine the association between cTnT elevations between 6 and 12 hours after coronary artery bypass grafting and in-hospital outcome. METHODS AND RESULTS:We prospectively studied 1722 patients undergoing isolated coronary artery bypass grafting. We assessed the association between conventional cTnT (749 patients) and high-sensitivity cTnT (hs-cTnT; 973 patients) 6 to 12 hours postoperatively with in-hospital major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, or stroke. The prespecified secondary outcome was a safety composite of MACCE, resuscitation, intensive care unit readmission or admission ?48 hours, inotrope or vasopressor use ?24 hours, or new-onset renal insufficiency. Among patients with a conventional cTnT measurement, 92 experienced a MACCE (12%) and 146 experienced a safety composite event (19%). Likewise, for hs-cTnT, 114 experienced a MACCE (12%) and 153 experienced a safety composite event (16%). Compared with cTnT ?200 ng/L, each 200-ng/L increment in cTnT was associated with a monotonous increase in the odds of MACCE and the safety composite outcome. Conventional and hs-cTnT demonstrated moderate discrimination for MACCE (areas under the fitted receiver operating characteristics curve, 0.72 and 0.77 for conventional and hs-cTnT, respectively) and the safety composite outcome (areas under the fitted receiver operating characteristics curve, 0.66 and 0.74 for conventional and hs-cTnT, respectively) and resulted in improved prognostic performance when added to the EuroSCORE. At a cutoff of 800 ng/L, conventional and hs-cTnT provided clinically relevant power to rule in MACCE and the safety composite outcome. CONCLUSIONS:cTnT levels assessed between 6 and 12 hours after coronary artery bypass grafting identify patients at increased risk of MACCE or other complications.

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Is endothelin gene polymorphism associated with postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting?

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