Ignite Creation Date:
2024-07-17 @ 11:21 AM
Last Modification Date:
2024-10-26 @ 3:33 PM
Study NCT ID:
NCT06475547
Status:
RECRUITING
Last Update Posted:
2024-07-09
First Post:
2024-06-20
Brief Title:
Inflammation and Postoperative Atrial Fibrillation in Cardiac Surgery
Sponsor:
Odense University Hospital
Organization:
Odense University Hospital
Study Overview
Official Title:
Inflammation and Postoperative Atrial Fibrillation in Cardiac Surgery
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Postoperative atrial fibrillation POAF is a common complication after cardiac surgery marked by an irregular and rapid heart rate and associated with increased morbidity longer hospital stays and higher costs Its complex pathophysiology involves atrial remodeling inflammation and autonomic dysregulation Surgical trauma and cardiopulmonary bypass trigger an inflammatory response releasing cytokines Epicardial fat around the heart secretes pro-inflammatory cytokines and its increased thickness is linked to higher inflammation and atrial fibrillation This study uses RNA sequencing RNA-seq to profile gene expression in epicardial fat identifying key genes involved in inflammation and metabolism By comparing patients with and without POAF RNA-seq reveals differentially expressed genes associated with postoperative atrial fibrillation
Detailed Description:
Postoperative Atrial Fibrillation POAF after Cardiac Surgery Postoperative atrial fibrillation is a common complication following cardiac surgery characterized by irregular and often rapid heart rate It is associated with increased morbidity prolonged hospital stays and higher healthcare costs The pathophysiology of POAF is complex and multifactorial involving atrial structural and electrical remodeling inflammation and autonomic dysregulation
Inflammation and Epicardial Fat Inflammation plays a significant role in the development of POAF Surgical trauma and cardiopulmonary bypass trigger a systemic inflammatory response releasing cytokines and other inflammatory mediators Epicardial fat the visceral fat depot around the heart is an active endocrine organ secreting pro-inflammatory cytokines and adipokines Increased epicardial fat thickness is associated with higher levels of inflammation and has been implicated in the pathogenesis of atrial fibrillation
RNA isolation and sequencing RNA sequencing RNA-seq can be used to investigate gene expression in epicardial fat in several impactful ways RNA-seq can profile gene expression to identify active genes in epicardial fat and their expression levels revealing key genes involved in inflammation and metabolism By comparing gene expression between groups such as patients with and without POAF RNA-seq can identify differentially expressed genes associated with atrial fibrillation
RNA-seq analyses The RNA sequencing data files were aligned to the hg38 reference genome using the Spliced Transcripts Alignment to a Reference STAR aligner and read counts in genes were quantified The resulting data matrix with unnormalized counts was loaded into RStudio together with patient metadata information eg age gender BMI smoking Differential expression analyses were conducted with DESeq2 using adjustment for different variables including type of tissue age of patients gender and BMI
Hypothesis The hypothesis that POAF may be influenced by pre-existing inflammation in epicardial fat in addition to the inflammation caused by surgical trauma
Objective
To compare inflammatory gene expression in epicardial fat between patients who develop POAF and those who do not after elective cardiac surgery
Study Design
A prospective cohort study including patients undergoing first-time elective cardiac surgery
Participants
Inclusion criteria Patients undergoing first-time elective cardiac surgery Exclusion criteria Patients with previous cardiac surgeries or emergency surgeries
Groups
POAF Group Patients who develop POAF Non-POAF Group Patients who do not develop POAF
Sample Collection
Epicardial fat samples will be collected during the time of surgery
RNA Isolation and Sequencing
Homogenize adipose tissue in TRIzol using ceramic beads Fastprep 24 MPBio Purify RNA using EconoSpin columns Epoch Prepare RNA libraries with NEBNext Ultra II RNA Library Prep Kit for Illumina Perform paired-end sequencing on the NovaSeq 6000 platform Illumina
Data Analysis
Align RNA-seq data to the hg38 genome using STAR aligner Quantify gene counts and perform differential expression analysis using DESeq2 Adjust for variables such as tissue type age gender and BMI
Outcome Measures
Compare inflammatory gene expression profiles between POAF and Non-POAF groups at the time of surgery
Inflammation and Epicardial Fat Inflammation plays a significant role in the development of POAF Surgical trauma and cardiopulmonary bypass trigger a systemic inflammatory response releasing cytokines and other inflammatory mediators Epicardial fat the visceral fat depot around the heart is an active endocrine organ secreting pro-inflammatory cytokines and adipokines Increased epicardial fat thickness is associated with higher levels of inflammation and has been implicated in the pathogenesis of atrial fibrillation
RNA isolation and sequencing RNA sequencing RNA-seq can be used to investigate gene expression in epicardial fat in several impactful ways RNA-seq can profile gene expression to identify active genes in epicardial fat and their expression levels revealing key genes involved in inflammation and metabolism By comparing gene expression between groups such as patients with and without POAF RNA-seq can identify differentially expressed genes associated with atrial fibrillation
RNA-seq analyses The RNA sequencing data files were aligned to the hg38 reference genome using the Spliced Transcripts Alignment to a Reference STAR aligner and read counts in genes were quantified The resulting data matrix with unnormalized counts was loaded into RStudio together with patient metadata information eg age gender BMI smoking Differential expression analyses were conducted with DESeq2 using adjustment for different variables including type of tissue age of patients gender and BMI
Hypothesis The hypothesis that POAF may be influenced by pre-existing inflammation in epicardial fat in addition to the inflammation caused by surgical trauma
Objective
To compare inflammatory gene expression in epicardial fat between patients who develop POAF and those who do not after elective cardiac surgery
Study Design
A prospective cohort study including patients undergoing first-time elective cardiac surgery
Participants
Inclusion criteria Patients undergoing first-time elective cardiac surgery Exclusion criteria Patients with previous cardiac surgeries or emergency surgeries
Groups
POAF Group Patients who develop POAF Non-POAF Group Patients who do not develop POAF
Sample Collection
Epicardial fat samples will be collected during the time of surgery
RNA Isolation and Sequencing
Homogenize adipose tissue in TRIzol using ceramic beads Fastprep 24 MPBio Purify RNA using EconoSpin columns Epoch Prepare RNA libraries with NEBNext Ultra II RNA Library Prep Kit for Illumina Perform paired-end sequencing on the NovaSeq 6000 platform Illumina
Data Analysis
Align RNA-seq data to the hg38 genome using STAR aligner Quantify gene counts and perform differential expression analysis using DESeq2 Adjust for variables such as tissue type age gender and BMI
Outcome Measures
Compare inflammatory gene expression profiles between POAF and Non-POAF groups at the time of surgery
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None