PeriOperative Medicine - Metabolic Inflexibility as a Mechanism for Myocardial Injury After Non-Cardiac Surgery (POM-MIMICS)

The goal of this observational study is to learn whether metabolic inflexibility, which means reduced ability of the body to switch between using fats and sugars for energy, is associated with myocardial injury after non-cardiac surgery (MINS) in adults undergoing major elective abdominal cancer surgery.

The main question it aims to answer is:

Does pre-operative metabolic inflexibility predict myocardial injury after non-cardiac surgery (MINS) within the first 72 hours after surgery?

Participants will continue with their usual surgical care and pre-planned CPET (which can measure metabolic flexibility). As part of the study, participants will:

• Have additional blood samples taken before and after surgery
• Have an echocardiogram and, where possible, muscle ultrasound
• Wear a wrist-worn activity monitor before surgery
• Have routine clinical and surgical information collected from their medical records
• Receive a follow-up phone call around 90 days after surgery

Study Overview

• Status: Not yet recruiting
• Conditions: MINS
• Intervention / Treatment: Other: Pre-operative Metabolic Inflexibility

Detailed Description

The POM-MIMIC study (PeriOperative Medicine - Metabolic Inflexibility as a mechanism for Myocardial Injury after Non-Cardiac Surgery) is a prospective, observational cohort study designed to improve perioperative risk stratification for myocardial injury after non-cardiac surgery (MINS). MINS affects up to 25% of patients undergoing major surgery and significantly increases long and short term mortality (1). Despite its clinical importance, the ability to predict MINS remains limited.

This study aims to evaluate if perioperative metabolic inflexibility, (the impaired ability of cells to adapt fuel usage to demand), is a driver of MINS. The study hypothesises that systemic metabolic dysfunction creates a state of cardiac vulnerability, priming the heart for injury when exposed to the multi-faceted immune/inflammatory and haemodynamic stressors of surgery and anaesthesia.

This study involves a prospective, multicentre observational cohort study of patients undergoing major abdominal cancer surgery. We will employ a deep, multi-modal phenotyping strategy to characterise each patient's intrinsic "metabolic resilience phenotype", with the goal of describing novel endotypes of MINS. We propose that the endotypes of MINS are:

Immune mediated / inflammatory endotype: Driven by pre-existing inflammation and perioperative immune dysregulation

Metabolic / proteomic endotype: Driven by metabolic inflexibility and may involve direct metabolic injury to cardiomyocytes, lipotoxicity, oxidative stress, and unique troponin fragment signatures

Type II MI / Ischaemic-dominant endotype: Classic supply-demand mismatch (e.g. from intraoperative hypotension), likely amplified in metabolically vulnerable hearts

Mixed phenotype: A combination of the above, reflecting the interaction of metabolic, immune, and haemodynamic stressors

The phenotyping strategy will integrate:

Functional assessment: Cardiopulmonary exercise testing (CPET) to quantify metabolic flexibility via substrate utilisation

Structural assessment: Advanced imaging (CT/ultrasound) to quantify body composition, including myosteatosis and cardiac steatosis, which are markers of metabolic vulnerability

Biological assessment: High-dimensional immunophenotyping, targeted proteomics to identify novel troponin sub-fragment signatures which may reveal if injury is ischaemic, metabolic, or inflammatory, as well as in vitro studies using patient serum on human IPSC-derived cardiomyocytes to test for direct metabotoxicity

An exploratory outcome of reviewing intra-operative data for hypotension, anaesthetic type, and haemodynamics will assess for the ischaemic phenotype.

The study will recruit 300 adult patients undergoing major elective abdominal cancer surgery at UCLH and participating CIPHER-2 sites (Southampton and Plymouth). Participants will undergo routine pre-operative CPET. CPET analysis will derive VO2 peak, anaerobic threshold, metabolic crosscover and substrate utilisation metrics (fat vs carbohydrate oxidation) - the operational measure of metabolic flexibility. They will also undergo routine echocardiography and ultrasound . At this time blood sampling will be taken for targeted and untargeted metabolomics / lipidomics, biobanking of plasma/serum and PBMCs for immunophenotyping. Intra-operatively, haemodynamic monitoring as well as anaesthetic technique will be recorded. Post-operatively, hs-cTnI will be taken on days 1, 2, and 3 to assess for MINS. On days 1, 3, and 5 blood will be taken for biobanking of plasma/serum and PBMCs for immunophenotyping. On day 1 additional biomarker sampling at 24 hours will assess proteomic troponin fragmentation analysis and for mass spectrometry. Outcomes of interest include the incidence of MINS, post operative complications, length of hospital stay, and 90-day recovery metrics. See figure 1 for the participant pathway. A mechanistic substudy (n=150) will investigate inflammatory and immune profiles to explore underlying biological drivers of cardiac susceptibility to stress, these tests will utilise the blood taken for biobanking on days 1, 3, and 5. A further substudy (n=150) will assess if changes in high sensitivity troponin (hs-cTnI levels) measured before and 2 hours after CPET, are associated with the incidence of MINS. An exploratory aim of the project will be to review if there is an association between pre- and post-operative wearable signals (such as activity and heart rate) and MINS. See figure 2 for the conceptual framework of the study.

The data from samples from the MIMICS study will power four interconnected work packages:

WP1 - Immune / inflammatory predictors of MINS (n=150 sub-cohort serum samples)

WP2 - Machine learning integration for MINS prediction

WP3 - Cellular mechanisms and preclinical validation (n=150 sub-cohort serum samples)

WP4 - Targeted proteomic analysis of troponin fragmentation

Through the findings of POM-MIMIC we hope to redefine understanding of MINS by identifying endotypes. This could lead to immediate clinical benefits by enhancing preoperative risk models through integration of CPET, imaging, and blood testing. These are feasible non-invasive tests that could be rapidly adopted into standard preoperative assessments. This study has translational value as once endotype is categorised, targeted therapies which have been proven to work (such as prehabilitation for metabolic inflexibility) can be employed to reduce perioperative complications and improve outcomes. On a broader scale, this work may inform policy on perioperative cardiac care and guide future clinical trials.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: John Whittle, MBBS, PhD; Phone Number: +44 203 447 3390; Email: j.whittle@ucl.ac.uk
• Study Contact Backup: Name: Rosalyn Hawkins, MBChB; Phone Number: +44 203 447 3390; Email: Rosalyn.hawkins.25@ucl.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants will be selected from patients receiving care at University College London Hospitals and other participating CIPHER-2 network hospitals, including Southampton and Plymouth. Potential participants will be identified through perioperative/pre-operative assessment pathways, including routine cardiopulmonary exercise testing clinics for patients being assessed before major surgery.

Description

Inclusion Criteria:

• Adults aged 18 or over
• Scheduled for major elective abdominal cancer surgery with planned overnight admission
• Scheduled for pre-operative CPET
• Able to provide written informed consent

Exclusion Criteria:

• Less than 18 years old
• Emergency surgery
• Unable or unwilling to undergo CPET
• Pregnancy
• Active sepsis
• End-stage organ failure (e.g. on dialysis)
• Participants without the mental capacity to consent
• Diagnosis of Type 1 Myocardial Infarction meeting the 4th Universal Definition criteria during the immediate pre-operative period. (Note: Added based on MINS definition context)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Major Abdominal Cancer Surgery Cohort; Adults aged 18 years and over who are scheduled to undergo major elective abdominal cancer surgery and are already referred for routine pre-operative cardiopulmonary exercise testing (CPET). This is an observational cohort study; no study-specific treatment or intervention will be assigned. Participants will continue with their usual surgical and perioperative care. The study will collect additional blood samples, imaging assessments, CPET-derived metabolic data, wearable activity data, and routine clinical information to evaluate whether pre-operative metabolic inflexibility is associated with myocardial injury after non-cardiac surgery.

Other: Pre-operative Metabolic Inflexibility; Pre-operative metabolic inflexibility will be assessed as an observational exposure using data from routine pre-operative cardiopulmonary exercise testing (CPET). CPET-derived measures of substrate utilisation, including fat and carbohydrate oxidation, will be used to evaluate the participant's ability to switch between energy sources during physiological stress. Additional blood-based metabolic, immune, and cardiac biomarker analyses may be used to further characterise metabolic phenotype. No treatment, procedure, or clinical management will be assigned or altered by the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of Myocardial Injury after Non-Cardiac Surgery	The primary outcome is the number of participants who develop myocardial injury after non-cardiac surgery (MINS) within 72 hours after surgery. MINS means evidence of heart muscle injury after an operation that is not heart surgery. It will be assessed using blood tests for high-sensitivity cardiac troponin I, a protein that is released into the blood when the heart muscle is injured. Blood samples will be taken on postoperative days 1, 2, and 3. Participants will be classified as having MINS if their postoperative troponin result is above the study-defined threshold for myocardial injury and the injury is judged to be related to the perioperative period rather than another clear non-surgical cause.	From surgery to 72 hours post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clavien-Dindo Complication Grade	Postoperative complications will be classified using the Clavien-Dindo grading system, which grades complications according to the treatment required to manage them. Higher grades indicate more serious complications. The outcome will report the number of participants with major postoperative morbidity, defined as a Clavien-Dindo grade III or higher complication.	From surgery to 30 days after surgery
Post-Operative Morbidity Survey (POMS)	Postoperative morbidity will be assessed using the Postoperative Morbidity Survey (POMS), a structured assessment that records whether participants have complications affecting different organ systems after surgery. The outcome will report the number of participants with postoperative morbidity identified by POMS assessment.	Postoperative day 7
Length of Hospital Stay	Length of hospital stay will be measured as the number of days from the date of surgery to the date the participant is discharged from hospital. This outcome will describe how long participants remain in hospital after their operation.	From surgery up to hospital discharge, an expected average of 7 days after surgery
Days Alive and Out of Hospital at 90 Days	Days alive and out of hospital at 90 days, also known as DAOH90, will be measured as the number of days the participant is alive and not admitted to hospital during the first 90 days after surgery. This outcome reflects postoperative recovery by combining survival, length of initial hospital stay, and any hospital readmissions within 90 days.	From surgery to 90 days after surgery

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Principal Investigator: John Whittle, MBBS, PhD, University College, London

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030

Study Registration Dates

• First Submitted: June 25, 2026
• First Submitted That Met QC Criteria: July 6, 2026
• First Posted (Actual): July 10, 2026

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: July 6, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Troponin; CPET; metabolic flexibility; Perioperative medicine; MINS; Cardiopulmonary Exercise Testing; abdominal cancer surgery
• Other Study ID Numbers: 200495; CC-I23-213-CIPHER-2 (Other Grant/Funding Number: CIPHER-2 grant / Becton Dickinson Ltd via University Hospital Southampton); 363389 (Other Identifier: Integrated Research Application System (IRAS), UK Health Research Authority)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be made publicly available. The study involves clinical data and blood-derived biomarker data from patients undergoing cancer surgery, and data sharing is restricted by participant confidentiality, consent, and data protection requirements. Results will be reported in aggregate form so that individual participants cannot be identified.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No