Dataset Information

Myocardial inflammation, injury and infarction during on-pump coronary artery bypass graft surgery.

ABSTRACT:

Background

Myocardial inflammation and injury occur during coronary artery bypass graft (CABG) surgery. We aimed to characterise these processes during routine CABG surgery to inform the diagnosis of type 5 myocardial infarction.

Methods

We assessed 87 patients with stable coronary artery disease who underwent elective CABG surgery. Myocardial inflammation, injury and infarction were assessed using plasma inflammatory biomarkers, high-sensitivity cardiac troponin I (hs-cTnI) and cardiac magnetic resonance imaging (CMR) using both late gadolinium enhancement (LGE) and ultrasmall superparamagnetic particles of iron oxide (USPIO).

Results

Systemic humoral inflammatory biomarkers (myeloperoxidase, interleukin-6, interleukin-8 and c-reactive protein) increased in the post-operative period with C-reactive protein concentrations plateauing by 48 h (median area under the curve (AUC) 7530 [interquartile range (IQR) 6088 to 9027] mg/L/48 h). USPIO-defined cellular myocardial inflammation ranged from normal to those associated with type 1 myocardial infarction (median 80.2 [IQR 67.4 to 104.8] /s). Plasma hs-cTnI concentrations rose by ?50-fold from baseline and exceeded 10-fold the upper limit of normal in all patients. Two distinct patterns of peak cTnI release were observed at 6 and 24 h. After CABG surgery, new LGE was seen in 20% (n?=?18) of patients although clinical peri-operative type 5 myocardial infarction was diagnosed in only 9% (n?=?8). LGE was associated with the delayed 24-h peak in hs-cTnI and its magnitude correlated with AUC plasma hs-cTnI concentrations (r?=?0.33, p?ConclusionPatients undergoing CABG surgery invariably have plasma hs-cTnI concentrations >10-fold the 99th centile upper limit of normal that is not attributable to inflammatory or ischemic injury alone. Peri-operative type 5 myocardial infarction is often unrecognised and is associated with a delayed 24-h peak in plasma hs-cTnI concentrations.

SUBMITTER: Alam SR

PROVIDER: S-EPMC5732376 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Myocardial inflammation, injury and infarction during on-pump coronary artery bypass graft surgery.

Alam Shirjel R SR Stirrat Colin C Spath Nick N Zamvar Vipin V Pessotto Renzo R Dweck Marc R MR Moore Colin C Semple Scott S El-Medany Ahmed A Manoharan Divya D Mills Nicholas L NL Shah Anoop A Mirsadraee Saeed S Newby David E DE Henriksen Peter A PA

Journal of cardiothoracic surgery 20171216 1

<h4>Background</h4>Myocardial inflammation and injury occur during coronary artery bypass graft (CABG) surgery. We aimed to characterise these processes during routine CABG surgery to inform the diagnosis of type 5 myocardial infarction.<h4>Methods</h4>We assessed 87 patients with stable coronary artery disease who underwent elective CABG surgery. Myocardial inflammation, injury and infarction were assessed using plasma inflammatory biomarkers, high-sensitivity cardiac troponin I (hs-cTnI) and c ...[more]

PMID: 29246240

Similar Datasets

Project description:Approximately 10% of patients undergoing cardiac surgery have perioperative myocardial injury. A recent genome-wide association study identified an association between myocardial infarction in nonsurgical populations and common genetic variants on chromosome 9p21. We hypothesized that these variants are also associated with perioperative myocardial injury after isolated primary coronary artery bypass graft surgery.In a prospective observational study of 846 Caucasian patients undergoing primary coronary bypass surgery at 2 US centers, we genotyped 61 linkage-disequilibrium tagging single nucleotide polymorphisms, encompassing 436 kbp of the 9p21 region. A multivariable logistic model was used to adjust for previously identified clinical covariates of perioperative myocardial injury. Perioperative myocardial injury was defined as a postoperative day 1 cardiac troponin I in the top 10th percentile (>9.13 microg/L) of the cohort. Multiple testing of single nucleotide polymorphisms was corrected for with family-wise errors.Prior myocardial infarction and longer cardiopulmonary bypass time were significant independent predictors of perioperative myocardial injury. Levels of postoperative cardiac troponin I were incrementally increased for each additional copy of the risk alleles of 3 single nucleotide polymorphisms: rs10116277, rs6475606, and rs2383207. Adjusted additive odds ratios ranged between 1.64 and 1.79 (asymptotic P value between 3.7 x 10(-3) and 6 x 10(-4)) and remained significantly associated with perioperative myocardial injury even after accounting for clinical covariates including severity of coronary disease, and multiple comparisons.We have now demonstrated that common genetic variants in the same 9p21 locus, previously known to be associated with myocardial infarction in nonsurgical populations, are also associated with perioperative myocardial injury after coronary artery bypass grafting. Further investigation is warranted to elucidate functional mechanisms.

Project description:Identification of patient subpopulations susceptible to develop myocardial infarction (MI) or, conversely, those displaying either intrinsic cardioprotective phenotypes or highly responsive to protective interventions remain high-priority knowledge gaps. We sought to identify novel common genetic variants associated with perioperative MI in patients undergoing coronary artery bypass grafting using genome-wide association methodology.107 secondary and tertiary cardiac surgery centres across the USA.We conducted a stage I genome-wide association study (GWAS) in 1433 ethnically diverse patients of both genders (112 cases/1321 controls) from the Genetics of Myocardial Adverse Outcomes and Graft Failure (GeneMAGIC) study, and a stage II analysis in an expanded population of 2055 patients (225 cases/1830 controls) combined from the GeneMAGIC and Duke Perioperative Genetics and Safety Outcomes (PEGASUS) studies. Patients undergoing primary non-emergent coronary bypass grafting were included.The primary outcome variable was perioperative MI, defined as creatine kinase MB isoenzyme (CK-MB) values ?10× upper limit of normal during the first postoperative day, and not attributable to preoperative MI. Secondary outcomes included postoperative CK-MB as a quantitative trait, or a dichotomised phenotype based on extreme quartiles of the CK-MB distribution.Following quality control and adjustment for clinical covariates, we identified 521 single nucleotide polymorphisms in the stage I GWAS analysis. Among these, 8 common variants in 3 genes or intergenic regions met p<10(-5) in stage II. A secondary analysis using CK-MB as a quantitative trait (minimum p=1.26×10(-3) for rs609418), or a dichotomised phenotype based on extreme CK-MB values (minimum p=7.72×10(-6) for rs4834703) supported these findings. Pathway analysis revealed that genes harbouring top-scoring variants cluster in pathways of biological relevance to extracellular matrix remodelling, endoplasmic reticulum-to-Golgi transport and inflammation.Using a two-stage GWAS and pathway analysis, we identified and prioritised several potential susceptibility loci for perioperative MI.

Project description:Mannose-binding lectin (MBL) is an important component of innate immunity and activator of the lectin complement pathway. Within the MBL2 gene are seven 5' "secretor" haplotypes that code for altered serum MBL levels and complement activation. However, recent evidence suggests that 3' MBL2 haplotypes may also modify MBL function and circulating levels. Because MBL and the lectin complement pathway have been implicated in cardiovascular injury, we investigated whether MBL2 haplotypes are independently associated with an increased risk of postoperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft surgery.Genotyping of 18 polymorphic sites within the MBL2 gene was performed in a prospective, longitudinal multi-institutional study of 978 patients undergoing primary coronary artery bypass graft-only surgery with cardiopulmonary bypass between August 2001 and May 2005. After adjustment for multiple comparisons by permutation testing, multivariate, stepwise logistic regression, including a score test, was performed controlling for patient demographics, preoperative risk factors, medications, and intraoperative variables to determine if MBL2 secretor haplotypes are independent predictors of PMI in whites undergoing primary coronary artery bypass graft surgery. Neither the 5' nor 3' MBL2 haplotypes alone were associated with an increased incidence of PMI. However, the incidence of PMI in whites (n=843) expressing the combined MBL2 5' LYQA secretor haplotype (CGTCGG) and 3' haplotype (CGGGT) was significantly higher than in whites not expressing the haplotype (38% versus 10%; P<0.007). Moreover, the combined MBL2 LYQA secretor haplotype was an independent predictor of PMI in whites after primary coronary artery bypass graft surgery after adjustment for other covariates (P<0.02; adjusted OR: 3.97; 95% CI: 1.30 to 12.07). The combined MBL2 LYQA secretor haplotype in whites was also an independent predictor of postoperative CKMB levels exceeding 60 ng/mL (P<0.02; adjusted OR: 4.48; 95% CI: 1.95 to 16.80). Inclusion of the combined MBL2 LYQA secretor haplotype improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.715 versus 0.705).The combined MBL2 LYQA secretor haplotype is a novel independent predictor of PMI and may aid in preoperative risk stratification of whites undergoing primary coronary artery bypass graft surgery.

Dataset Information

Myocardial inflammation, injury and infarction during on-pump coronary artery bypass graft surgery.

Background

Methods

Results

Publications

Myocardial inflammation, injury and infarction during on-pump coronary artery bypass graft surgery.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets