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 (Ob-Card)

An Observational 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

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 Overview

• Status: Recruiting
• Conditions: C.Surgical Procedure; Cardiac

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Tracy Kumar; Phone Number: 01162583039; Email: tk98@leicester.ac.uk

Study Locations

• United Kingdom
  • Leicestershire
    • Glenfield, Leicestershire, United Kingdom, LE3 9QP
      • Recruiting
      • England

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study will be carried out at a large tertiary academic cardiac surgery unit in the UK; the University Hospitals of Leicester NHS Trust. This unit performs over 1,200 major cardiac procedures per year, of which 600 are patients undergoing coronary artery bypass grafting

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post surgery inotrope score	inotrope score measured up to 48 hours post-surgery	inotrope score measured up to 48 hours post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in expression of target genes	from right atrial biopsies	Collected at the time of surgery
Changes in epigenetic regulation of target genes from left atrial biopsies.	histone acetylation, DNA methylation	Collected at the time of surgery
Changes in mitochondrial function	in atrial biopsies and buffy coats of blood samples collected before and after surgery	before and after sugery (up to 12 hours post surgery)
Myocardial Injury	defined by post cardiac surgery serum Troponin levels	baseline and 24 hours
Acute kidney injury	defined by serum creatinine level postoperatively, as per the KDIGO criteria	baseline, and up to 15 days post surgery (discharge)
Perioperative clinical characteristics	Perioperative clinical characteristics	Collected pre op
Perioperative medications.	Perioperative medications.	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	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)	baseline, and up to 96 hours post surgery
Data on demographics	Height in cms	Pre Op
Data on demographics	Weight in kgs	Pre Op

Collaborators and Investigators

• Sponsor: University of Leicester
• Investigators: Principal Investigator: Gavin Murphy, University of Leicester; Principal Investigator: Filiberto Serraino, University of Leicester

Publications and helpful links

General Publications

• Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995 Oct;23(10):1638-52. doi: 10.1097/00003246-199510000-00007.
• Adebayo AS, Roman M, Zakkar M, Yusoff S, Gulston M, Joel-David L, Anthony B, Lai FY, Murgia A, Eagle-Hemming B, Sheikh S, Kumar T, Aujla H, Dott W, Griffin JL, Murphy GJ, Wozniak MJ. Gene and metabolite expression dependence on body mass index in human myocardium. Sci Rep. 2022 Jan 26;12(1):1425. doi: 10.1038/s41598-022-05562-8.
• ARDS Definition Task Force; Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2016
• Primary Completion (Estimated): October 7, 2024
• Study Completion (Estimated): October 7, 2024

Study Registration Dates

• First Submitted: July 19, 2016
• First Submitted That Met QC Criteria: September 15, 2016
• First Posted (Estimated): September 20, 2016

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 9, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: 0574

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED