A Case Control Study to Identify the Role of Epigenetic Regulation of Genes Responsible for Energy Metabolism and Mitochondrial Function in the Obesity Paradox in Cardiac Surgery

University of Leicester80 enrolled

Overview

This is a prospective, single-centre case control comparison of expression of target genes responsible for energy utilisation, mitochondrial function and oxidative stress and levels of histone acetylation/ DNA methylation in obese and non-obese adult cardiac surgery patients. The study aims to test several inter-related hypotheses in a consecutive sequence of patients undergoing coronary artery bypass grafting.

Study Type

OBSERVATIONAL

Enrollment

Conditions

C.Surgical Procedure; Cardiac

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with pre-existing paroxysmal, persistent or chronic atrial fibrillation, Exclusion Criteria: * Patients with pre-existing inflammatory state: sepsis undergoing treatment, acute kidney injury within 5 days, chronic inflammatory disease, congestive heart failure. * Emergency or salvage procedure. * Ejection fraction \<30 %. * Patient in a critical preoperative state (Kidney Disease: Improving Global Outcomes (KDIGO) Stage 3 AKI \[20\] or requiring inotropes, ventilation or intra-aortic balloon pump). * Pregnancy.

Locations (1)

England

Glenfield, Leicestershire, United Kingdom

Outcomes

Primary Outcomes

Post surgery inotrope score

inotrope score measured up to 48 hours post-surgery

Time frame: inotrope score measured up to 48 hours post-surgery

Secondary Outcomes

Changes in expression of target genes

from right atrial biopsies

Time frame: Collected at the time of surgery

Changes in epigenetic regulation of target genes from left atrial biopsies.

histone acetylation, DNA methylation

Time frame: Collected at the time of surgery

Changes in mitochondrial function

in atrial biopsies and buffy coats of blood samples collected before and after surgery

Time frame: before and after sugery (up to 12 hours post surgery)

Myocardial Injury

defined by post cardiac surgery serum Troponin levels

Time frame: baseline and 24 hours

Acute kidney injury

defined by serum creatinine level postoperatively, as per the KDIGO criteria

Time frame: baseline, and up to 15 days post surgery (discharge)

Perioperative clinical characteristics

Time frame: Collected pre op

Perioperative medications.

Time frame: Collected pre op

Data to calculate Multiple Organ Dysfunction (MOD) score.

To calculate the MOD score, the Respiratory Function (calculated as partial pressure of oxygen (PaO2) divided by fraction of inspired oxygen (FiO2)), Cardiovascular (Pressure adjusted heart rate (PAR) ), Renal (Serum Creatinine), Hepatic (serum bilirubi

Time frame: baseline, and up to 96 hours post surgery

Data to capture Acute Respiratory Distress Syndrome (Berlin criteria ARDS).

Acute Lung Injury (ALI) non-ARDS, ARDS. To define these different categories of acute lung injury, the Positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) will be recorded in the CRF at time points: Pre-OP, ICU, 12 hrs post-op,24hrs post-op,48hrs post-op,72hrs post-op and 96hrs post-op. Along with the PaO2/FiO2 ratio, it will then be possible to categorise patients into the above definitions of acute lung injury as follows: ALI non-ARDS (200 mmHg \<PaO2/FiO2\<300 mmHg, regardless of PEEP),ARDS (PaO2/FiO2\<200 mmHg, regardless of PEEP), mild Berlin Definition(200mmHg \<PaO2/FiO2\<300mmHg with PEEP \> 5cm H2O),moderate Berlin Definition(100mmHg \<calculated as partial pressure of oxygen divided by fraction of inspired oxygen PaO2/FiO2 \< 200mmHg with PEEP \> 5cm H2O) and Severe Berlin Definition (PaO2/FiO2 \< 100mmHg with PEEP \> 5cm H2O)

Time frame: baseline, and up to 96 hours post surgery

Data on demographics

Height in cms

Time frame: Pre Op