Effect of the ligament of Marshall excision during minimally invasive cardiac surgery-coronary artery bypass grafting (MICS-CABG) on the prevention of postoperative new-onset atrial fibrillation (LOMEX-AF): study protocol for a randomised controlled trial

Abstract

Introduction

Postoperative atrial fibrillation (POAF) remains one of the most common complications following coronary artery bypass grafting (CABG), including minimally invasive cardiac surgery-CABG (MICS-CABG). The ligament of Marshall (LOM), containing myocardial fibres and rich autonomic innervation, has been implicated in atrial arrhythmogenesis. Despite evidence that catheter ablation targeting the LOM or surgical interruption during conventional CABG can be effective, prophylactic surgical excision of the LOM during MICS-CABG has not been evaluated in randomised controlled trials (RCTs).

Methods and analysis

The Ligament of Marshall Excision for the Prevention of Postoperative New-Onset Atrial Fibrillation (LOMEX-AF) trial is a single-centre, prospective, triple-blind (participants, outcome assessors, statisticians) RCT. Adults 30–80 years scheduled for elective MICS-CABG who meet inclusion/exclusion criteria will be randomised to Standard MICS-CABG with posterior left pericardiotomy (control) or the same procedure plus excision of a segment of the LOM (intervention). Resected tissue will be fixed for histopathology. Primary outcome: new-onset POAF during index hospitalisation defined as atrial fibrillation or atrial flutter lasting ≥30 s detected by ECG/telemetry. Secondary outcomes include frequency and duration of episodes, need for Class I/III antiarrhythmics or electrical cardioversion, intensive care unit and hospital length of stay, mechanical ventilation time and reoperation for bleeding. Sample size: 340 per arm (n=680 total) to detect a 50% relative reduction from an estimated 17% control event rate with 90% power, two-sided α=0.05, allowing 5% attrition. Primary analysis: intention-to-treat; categorical comparisons by χ² or Fisher exact test; continuous variables by t-test or Mann-Whitney U as appropriate; analyses performed in R.

Ethics and dissemination

The study has been approved by the institutional ethics committee of Peking University Third Hospital, Beijing, China (IRB00006761-M20250847. 11 October 2025). Written informed consent will be obtained from all participants before enrolment. The trial will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice principles and applicable national regulations. The findings will be disseminated through publication in peer-reviewed journals and presentation at academic conferences.

Trial registration number

ChiCTR2500110913.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• This study is a prospective randomised controlled trial designed to evaluate the effect of ligament of Marshall excision during minimally invasive coronary artery bypass grafting on the prevention of postoperative atrial fibrillation (POAF).

• The trial adopts a triple-blind design, with participants, outcome assessors and data analysts blinded to group allocation, reducing the risk of assessment and analytical bias.

• Continuous electrocardiographic monitoring during hospitalisation ensures reliable detection of POAF events.

• The intervention is integrated into routine surgical procedures, which enhances the clinical applicability and procedural feasibility of the study.

• The sample size was calculated to detect a reduction in POAF incidence from 17.0% to 8.5%, based on previous studies of low-risk surgical interventions for POAF prevention and our preliminary experience. If the true treatment effect is smaller than anticipated, the precision of the estimated treatment effect may be limited and evaluation of smaller but clinically meaningful reductions may require larger multicentre studies.

Structured summary

The structured summary of the Ligament of Marshall Excision for the Prevention of Postoperative New-Onset Atrial Fibrillation (LOMEX-AF) trial protocol is provided in table 1.

Table 1. Structured summary of the LOMEX-AF trial protocol.

Item	Description
Primary registry and trial identifying number (4)	Trial registration: https://www.chictr.org.cn Registration number: ChiCTR2500110913 (22 October 2025).
Primary sponsor and contact information (3b)	Department of Cardiac Surgery, Peking University Third Hospital; Yunpeng Ling, micsling@pku.edu.cn.
Role of sponsor and funder (3c)	This study is a researcher-initiated project, supported by the researcher’s funding: Peking University Third Hospital Hospital-level Cohort Construction Project (BYSYDL2022012) and Peking University Third Hospital Key Clinical Project (BYSYZD2023015).
Study type	This is a single-centre, prospective, parallel-group, randomised controlled superiority trial with 1:1 allocation. Participants undergoing elective MICS-CABG will be randomised to intervention or control in equal proportions; the study is triple-blind, with participants, outcome assessors and statistical analysts masked to group assignment.
Countries of recruitment	China
Date of first enrolment (planned)	24 October 2025
Sample size	680 (planned)
Ethics review	The study has been approved by the institutional ethics committee of Peking University Third Hospital (IRB00006761-M20250847 11 October 2025).
Individual trial participant data sharing statement	The IPD data underlying this study will be shared on reasonable request to the corresponding author (YL, micsling@pku.edu.cn).

IPD, individual participant data; LOMEX-AF, Ligament of Marshall Excision for the Prevention of Postoperative New-Onset Atrial Fibrillation; MICS-CABG, minimally invasive cardiac surgery-coronary artery bypass grafting.

Protocol version

Protocol version 1.0 (12 September 2025).

Introduction

Postoperative atrial fibrillation (POAF) is the most common form of secondary atrial fibrillation (AF) (≈30%)¹ and a frequent complication after coronary artery bypass grafting (CABG) (20–40%).^{2 3} Although minimally invasive or totally endoscopic/robotic CABG can reduce surgical trauma and thereby lower POAF incidence to some extent, rates of 4.8–18.4% are still observed.^{4 5} POAF is strongly associated with prolonged hospitalisation, increased medical costs, stroke, heart failure, myocardial infarction and higher long-term mortality.^{6 7} Therefore, prevention of POAF is an important step to improve postoperative patient outcomes.

POAF typically arises from the interaction of a ‘patient-susceptible substrate’ (clinical and anatomical factors) and ‘surgery-related triggers’ (perioperative insults). Over the past 20 years, numerous clinical studies and meta-analyses have identified consistent risk factors such as advanced age, hypertension, heart failure, chronic obstructive pulmonary disease, diabetes and obesity.^{8 9} However, operative factors that cause tissue injury should not be overlooked. Median sternotomy, pericardial effusion, systemic inflammatory response from cardiopulmonary bypass, atrial wall stretch and suture, and perioperative autonomic imbalance between sympathetic and parasympathetic systems can all precipitate POAF.10,17 The Posterior Left Pericardiotomy for the Prevention of Atrial Fibrillation After Cardiac Surgery trial by Gaudino et al showed that posterior left pericardiotomy significantly reduced POAF after CABG, aortic valve or ascending aortic procedures (17% vs 32%; p=0.0007; OR 0.44 (95% CI 0.27 to 0.70)),¹⁸ without increasing postoperative complications. The cardiac autonomic nervous system plays a crucial role in POAF pathogenesis. Yang et al reported in a single-centre prospective randomised controlled trial that partial cardiac denervation reduced POAF after CABG (18.1% vs 31.6%; p=0.001; relative risk (RR) 0.57 (95% CI 0.41 to 0.81)).¹⁹ These results provided a solid theoretical basis for further research on the prevention of POAF, and offer a pioneering approach in terms of operability and safety.

The ligament of Marshall (LOM) is a fibrous remnant of the embryonic left superior vena cava whose arrhythmogenicity is closely linked to its complex histological composition. In addition to myocardial sleeve cells, fat, fibrous tissue and vessels that can form a substrate for re-entry, the LOM contains abundant autonomic ganglionated plexi that facilitate trigger activity; postoperative sympathetic surges mediated via these structures are important precipitants of POAF.^{20 21} Management of the LOM has attracted increasing attention in electrophysiology, with the vein of Marshall (VOM) considered an effective target to improve outcomes of catheter ablation for AF.²² The Vein of Marshall Ethanol Infusion for Persistent Atrial Fibrillation trial suggested that adjunctive ethanol infusion of the VOM during catheter ablation further reduced AF recurrence.²³ In surgical practice, Cox-Maze IV procedures routinely interrupt the LOM when treating paroxysmal or persistent AF, without increasing operative risk.

This study will supplement clinicians’ understanding of POAF and partial cardiac denervation interventions and may provide a simple, easily implemented, low-risk surgical approach to reduce perioperative AF, decrease use and adverse effects of antiarrhythmic drugs, and improve postoperative haemodynamics and early quality of life.

During MICS-CABG, resection of the LOM does not require additional complex or high-difficulty exposure. Via a left anterior lateral intercostal small incision, after pericardiotomy and routine suspension the LOM is readily exposed in the operative field, facilitating the procedure. Compared with conventional median sternotomy CABG, this approach reduces excessive manipulation of the left heart and related surgical stimulation.

Previous prospective randomised trials have sometimes included atrial premature beats and supraventricular tachycardia (SVT) within POAF definitions, whereas true POAF is mechanistically distinct from broader atrial ectopy and SVT. Therefore, this study will strictly define POAF to include only AF and atrial flutter. Gaudino et al demonstrated that posterior left pericardiotomy significantly lowers POAF after CABG, aortic valve and ascending aortic surgery.¹⁸ In our centre’s MICS-CABG practice there is no subxiphoid pericardial or mediastinal drain placement; routine left posterior pericardial windowing and closed left pleural drainage are performed to ensure adequate postoperative drainage and reduce pericardial effusion. These measures are applied to both intervention and control groups, making LOM management the sole variable and allowing more accurate assessment of its preventative effect on POAF. This is a major strength of the study.

LOM histology is heterogeneous across individuals. We will perform subgroup analyses within the intervention arm based on postoperative pathological findings, quantifying proportions and dimensions of fibrous tissue, ganglionic elements, inflammatory cells, venous structures and myocardial cells to investigate the histological mechanisms by which LOM resection may prevent POAF. This exploratory analysis represents a novel aspect of the trial.

Compared with conventional median sternotomy CABG, the trial design already incorporates measures (avoiding sternotomy and routine pericardial windowing) that reduce POAF risk in all participants, thereby enhancing procedural safety. The primary aim is to determine whether isolated LOM resection further lowers POAF incidence.

MICS-CABG avoids sternotomy and performs left posterior pericardiotomy and drainage. These two measures reduce injury and inflammatory stimulation of the pericardial environment, and to some extent reduce the incidence of POAF after CABG. Therefore, we set this as the comparator, which is also the routine surgical procedure in our centre.

Objectives

Primary objective: Evaluate whether intraoperative LOM excision reduces incidence of new-onset POAF during index hospitalisation after MICS-CABG.

Secondary and exploratory objectives: Compare AF burden (frequency, duration), need for antiarrhythmic therapy or cardioversion, intensive care unit (ICU)/hospital length of stay (LOS), ventilation time, reoperation for bleeding, transfusions, conversion to on-pump CABG, in-hospital major adverse cardiovascular and cerebrovascular events (MACCEs); correlate LOM histopathology with arrhythmic outcomes.

Methods and analysis

Patient and public involvement

Patients and/or the public were not involved in the design, conduct, reporting or dissemination plans of this trial. Trial procedures, outcome measures and consent materials were developed by the clinical and research team based on clinical practice and current evidence without direct patient or public consultation.

Trial design

This is a single-centre, prospective, parallel-group, randomised controlled superiority trial with 1:1 allocation. Participants undergoing elective MICS-CABG will be randomised to intervention or control in equal proportions; the study is triple-blind, with participants, outcome assessors and statistical analysts masked to group assignment. The primary efficacy analysis will be conducted according to the intention-to-treat (ITT) principle. The trial flowchart is shown in figure 1.

Figure 1. Patient screening procedure and trial flowchart. ICU, intensive care unit; LOM, ligament of Marshall; MICS-CABG, minimally invasive cardiac surgery-coronary artery bypass grafting.

Participants, interventions and outcomes

Trial setting

Department of Cardiac Surgery, Peking University Third Hospital, Beijing, China.

Characteristics of the people who are needed for the trial

The characteristics of the participants expected to be included in the trial are summarised in table 2.

Table 2. Characteristics of the participants expected to be included in the LOMEX-AF trial.

Characteristic	The people we would expect to see included
Age	Adults aged 30–80 years are eligible for inclusion. The expected mean age is approximately 65±10 years based on institutional data.
Sex	Sex will be recorded as male or female as documented in the medical record.
Gender	Gender identity is not separately collected in this trial. Sex as recorded in medical records will be used for analysis.
Race, ethnicity and ancestry	Ethnicity is not a primary variable in this trial but will be recorded as documented in hospital records if available.
Socio-economic status	Socio-economic status is not formally assessed in this trial.
Geographical location	Participants are recruited at Peking University Third Hospital, Beijing, China, an urban tertiary referral centre.
Other characteristics relevant to the trial	None.

LOMEX-AF, Ligament of Marshall Excision for the Prevention of Postoperative New-Onset Atrial Fibrillation.

Eligibility criteria for participants

Inclusion criteria: (1) Age between 30 and 80 years; (2) diagnosed with coronary artery disease meeting the surgical indications for coronary revascularisation. Scheduled to undergo minimally invasive cardiac surgery-CABG (MICS-CABG). (3) Able to provide written informed consent prior to participation.

Exclusion criteria: (1) patients with preoperative haemodynamic instability requiring emergency surgery; (2) preoperative history of paroxysmal AF or persistent AF; (3) patients with preoperative implanted pacemakers; (4) patients with an ejection fraction <40%, a left ventricular end-diastolic diameter >60 mm, left ventricular wall tumour or severe arrhythmia, who are prone to haemodynamic instability during surgery; (5) combined mitral stenosis or mitral insufficiency of moderate degree or above; (6) concurrent valve surgery or other intracardiac corrective surgery; (7) patients with previous renal insufficiency requiring haemodialysis; (8) requirement for preoperative intra-aortic balloon pump (IABP) or extracorporeal membrane oxygenation (ECMO) circulatory support; (9) preoperative administration of antiarrhythmic drugs other than beta-blockers, such as propafenone and amiodarone; (10) previous cardiac surgery or thoracic surgery; (11) poor pulmonary function, preoperative resting unoxygenated state of arterial blood gas analysis oxygen partial pressure <60 mm Hg.

Eligibility criteria for sites and those delivering interventions

This is a single-centre trial conducted at Peking University Third Hospital, a tertiary academic referral centre with a high-volume cardiac surgery programme. The centre performs more than 800 well-established CABG procedures annually. The institution has extensive experience in off-pump coronary surgery and in minimally invasive cardiac surgical techniques.

All surgical procedures are performed by board-certified cardiac surgeons with extensive experience in minimally invasive CABG. Each participating surgeon has performed more than 500 MICS-CABG procedures prior to trial initiation. To ensure procedural consistency, the technique of LOM identification and excision was standardised before trial commencement.

Who will take informed consent?

Eligible patients will be identified during preoperative assessment. A trained investigator who is not directly responsible for postoperative outcome assessment will provide detailed verbal and written information regarding the study objectives, procedures, potential risks and benefits. Participants will be given sufficient time to consider participation and to ask questions before signing the consent form. Participation is entirely voluntary, and patients may withdraw at any time without affecting their medical care. For patients unable to provide consent, enrolment will not proceed.

Additional consent provisions for collection and use of participant data and biological specimens

Excised LOM tissue obtained during surgery will be used for histopathological analysis as part of this study. Participants will provide specific consent for the collection and analysis of biological specimens. All specimens will be coded and de-identified prior to analysis. Tissue samples will be stored securely at Peking University Third Hospital. No genetic testing will be performed. Any future use of biological specimens beyond the scope of the present study will require additional ethical approval and, if necessary, additional participant consent.

Intervention and comparator

Intervention and comparator description

Surgical approach (both groups)

A 4–6 cm skin incision is made in the left fourth or fifth intercostal space. Subcutaneous tissues and intercostal muscles are dissected to enter the left pleural cavity, and single-lung ventilation is instituted. The left internal mammary artery is harvested routinely for use, and the saphenous vein or radial artery is obtained as additional conduit material as needed. The pericardium is opened and suspended, and standard MICS-CABG anastomoses are performed. A left-sided pericardial window is created to allow blood to drain into the pleural space to improve surgical exposure and facilitate placement of the postoperative chest drain. To reduce postoperative pain from the intercostal drain that might affect POAF assessment, a local nerve block with lidocaine is performed prior to skin closure and a patient-controlled analgesia pump is provided routinely.

Intervention group: The LOM between the left atrial appendage and the left pulmonary veins is exposed, mobilised and excised using minimally invasive scissors. The excised LOM specimen is immediately placed in formalin for fixation and sent to pathology for analysis.

Control group: No LOM excision is performed, although the region is inspected. The LOM region will only be visually identified as part of routine anatomical orientation during exposure for coronary anastomosis. No additional dissection, mobilisation, cauterisation, clipping or excision of the LOM region will be performed. Only the gross anatomical appearance of the LOM region will be recorded.

Criteria for discontinuing or modifying allocated intervention/comparator

The allocated intervention may be discontinued or modified under the following circumstances:

1. Intraoperative findings that render LOM identification unsafe or technically infeasible.

2. Significant intraoperative bleeding or haemodynamic instability requiring urgent conversion to on-pump CABG.

3. Unexpected anatomical variation precluding safe resection.

4. Participant withdrawal of consent prior to surgery.

Any modification or discontinuation of the allocated intervention will be documented with justification.

Participants will remain in the ITT analysis population regardless of intervention discontinuation.

Strategies to improve adherence to intervention/comparator

To ensure adherence to the intervention protocol:

1. A standardised operative procedure for LOM identification and resection was developed prior to trial initiation.

2. All participating surgeons were trained and agreed on the operative steps.

3. Intraoperative findings and procedural details will be documented in a structured surgical record.

4. Postoperative rhythm monitoring will follow a standardised protocol in both groups.

Adherence to the allocated intervention will be reviewed periodically by the study steering committee.

Concomitant care permitted or prohibited during the trial

All participants will receive standard perioperative care according to institutional protocols. Prophylactic antiarrhythmic therapy will not be routinely administered unless clinically indicated. Beta-blockers and other cardiovascular medications will be prescribed according to standard guidelines and applied equally in both groups. Postoperative management, including electrolyte correction and haemodynamic optimisation, will follow the same standardised protocol in both groups. No additional surgical ablation procedures for AF will be performed during the index surgery.

Ancillary and post-trial care

All participants will receive standard perioperative and postoperative care according to institutional protocols. In the event of trial-related adverse events (AEs), appropriate medical treatment will be provided by Peking University Third Hospital at no additional cost to the participant beyond standard medical insurance coverage. No specific post-trial interventions are planned. Participants will continue routine clinical follow-up as per standard cardiac surgical practice.

Outcomes

Primary outcome:

The primary outcome is the incidence of POAF occurring during hospitalisation. POAF is defined as new-onset AF or atrial flutter lasting ≥30 s detected by: standard 12-lead electrocardiography, or continuous bedside ECG monitoring, or telemetry monitoring. Diagnostic criteria include: irregular RR intervals without discernible P waves, or replacement of P waves by consistent flutter (F) waves. All ECG recordings will be independently reviewed by two blinded investigators. In case of disagreement, a certified cardiologist will adjudicate the final diagnosis.

The primary endpoint will be analysed as a binary variable (proportion of patients experiencing POAF).

Secondary outcomes:

1. Frequency and cumulative duration of AF or atrial flutter episodes during hospitalisation—continuous variable, derived from ECG monitoring records.

2. Requirement for antiarrhythmic therapy, including use of Class I or Class III antiarrhythmic drugs (Vaughan Williams classification), electrical cardioversion—binary variable.

3. Length of postoperative hospital stay, days from surgery to discharge—continuous variable.

4. Duration of postoperative mechanical ventilation, hours from ICU admission to extubation—continuous variable.

5. Reoperation for postoperative bleeding—binary variable.

Safety outcomes:

1. Conversion to on-pump CABG during surgery.

2. Postoperative pericardial effusion requiring drainage.

3. Postoperative blood transfusion volume.

4. Requirement for intraoperative or postoperative IABP or ECMO support.

5. MACCEs, defined as a composite of: all-cause mortality, non-fatal myocardial infarction, stroke, ischaemia-driven target vessel revascularisation.

Safety outcomes will be recorded from surgery until hospital discharge and analysed descriptively between groups.

Continuous variables will be expressed as mean±SD or median (IQR), depending on distribution. Categorical variables will be presented as frequencies and percentages.

Harms

All AEs and serious AEs (SAEs) occurring from the time of surgery until hospital discharge will be recorded. SAEs are defined as events resulting in death, life-threatening conditions or significant disability.

AEs of special interest include:

1. Reoperation for bleeding.

2. Stroke.

3. Myocardial infarction.

4. Conversion to on-pump CABG.

5. All-cause mortality.

AEs will be assessed systematically during hospitalisation and classified according to standard clinical definitions. All SAEs will be reported to the institutional ethics committee in accordance with regulatory requirements. Safety outcomes will be reported descriptively and compared between groups.

Participant timeline

The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) chart depicts the participant timeline of the trial. (figure 2)

Figure 2. SPIRIT chart. This participant timeline applies for patients in the RCT part of the study. AF, atrial fibrillation; LOM, ligament of Marshall; MICS-CABG, minimally invasive cardiac surgery-coronary artery bypass grafting; POAF, postoperative atrial fibrillation; RCT, randomised controlled trial; SPIRIT, Standard Protocol Items: Recommendations for Interventional Trials.

Sample size

The assumed event rate was based on institutional observational data and published evidence.^{12 24} In a preliminary observational cohort conducted at our centre, the incidence of POAF following MICS-CABG was approximately 15–20%. In an institutional cohort of patients undergoing concomitant LOM resection, the observed POAF incidence was approximately 6–9%. Based on these institutional observations and mechanistic evidence supporting the arrhythmogenic role of the LOM,^{20 25 26} we conservatively assumed a reduction from 17% in the control group to 8.5% in the intervention group. Using a two-sided alpha of 0.05 and a power of 90%, 322 patients per group are required. Assuming 5% attrition, the total planned enrolment is 680 patients. If the true effect size is smaller than anticipated, the precision of the estimated treatment effect may be limited; however, the trial is designed to detect a clinically meaningful difference based on the prespecified assumptions.

Recruitment

Participants will be recruited from patients scheduled to undergo minimally invasive CABG (MICS-CABG) at the Department of Cardiac Surgery, Peking University Third Hospital. The annual volume of MICS-CABG at our centre is approximately 600–700 cases, ensuring an adequate pool of potentially eligible participants.

Consecutive patients admitted for elective MICS-CABG will be screened against the predefined inclusion and exclusion criteria. Eligible patients will be approached by the study team during their preoperative hospitalisation, provided with trial information and invited to give written informed consent.

Recruitment is planned from October 2025 to January 2027 and has already commenced. A total of 680 participants (approximately 340 per group) will be enrolled, allowing for an anticipated dropout rate of 5%.

Assignment of interventions-randomisation

Sequence generation: who will generate the sequence

The randomisation sequence will be generated by an independent statistician with expertise in biostatistics who is not involved in participant recruitment, clinical management or outcome assessment. The sequence will be created using R software (V.4.4.2).

Sequence generation: type of randomisation

Block randomisation will be used with variable block sizes of 4 and 6 to ensure approximate balance between the intervention and control groups throughout the recruitment period. Participants will be allocated to the intervention or control group in a 1:1 ratio.

Allocation concealment mechanism

Allocation concealment will be ensured through a secure, central, web-based randomisation module embedded in the Research Electronic Data Capture (REDCap) data capture platform. The randomisation list generated in R will be stored within REDCap and will not be accessible to investigators in an unblinded form. After completing preoperative assessments, confirming eligibility and obtaining written informed consent, study staff will enter the participant’s information into REDCap. The system will then automatically assign the participant to either the intervention or control group according to the preloaded randomisation sequence. Thus, group allocation will remain concealed until the moment of randomisation, preventing foreknowledge of treatment assignment by enrolling investigators.

Implementation

Eligible participants will be enrolled by the study investigators after written informed consent is obtained. The enrolling investigators will not have access to the randomisation sequence. Group assignment will be revealed only after patient enrolment and immediately prior to surgery.

Assignment of interventions-blinding

Who will be blinded

The following parties will be blinded to treatment allocation:

1. Trial participants.

2. Outcome assessors.

3. Statistician.

Postoperative care providers, including ICU staff and ward physicians, will not be informed of the allocation and will provide standardised perioperative management according to institutional protocols.

Due to the nature of the surgical procedure, the operating surgeon cannot be blinded to group allocation.

How will blinding be achieved

Blinding will be maintained as follows:

1. Group allocation will not be disclosed to participants at any time during hospitalisation.

2. Medical records will not explicitly state whether the LOM was resected.

3. Outcome assessors responsible for ECG interpretation will be independent and unaware of treatment allocation.

4. Data sets provided to statisticians will be coded using anonymised group labels (eg, Group A and Group B).

5. Postoperative care protocols will be identical between groups to minimise performance bias.

6. Because the intervention involves resection of the LOM during minimally invasive CABG without additional external incisions, the procedures appear clinically similar to participants.

Procedure for unblinding

Unblinding will only be permitted in the event of a medical emergency where knowledge of the allocated intervention is deemed essential for patient management. The decision to unblind will be made by the principal investigator in consultation with the study steering committee. If unblinding occurs, the reason, timing and personnel involved will be documented. Routine postoperative management does not require knowledge of group allocation; therefore, unblinding is expected to be rare. Data analysts will remain blinded until completion of the primary statistical analysis.

Data collection and management

Plans for assessment and collection of outcomes

All trial data will be collected prospectively during hospitalisation using standardised case report forms (CRFs).

To promote data quality:

1. All research staff will receive standardised training prior to trial initiation.

2. A detailed data dictionary will be developed.

3. Key outcome variables will be verified by a second investigator.

4. Periodic internal audits will be conducted by the study steering committee.

Plans to promote participant retention and complete follow-up

Because the primary and secondary outcomes are assessed during hospitalisation, loss to follow-up is expected to be minimal.

Participants will receive routine postoperative monitoring as part of standard cardiac surgical care.

If a participant discontinues the allocated intervention intraoperatively (eg, conversion to on-pump CABG), outcome data will continue to be collected according to the ITT principle.

In our centre, patients are usually discharged home once they are haemodynamically stable, have no uncontrolled arrhythmia or active bleeding, show acceptable wound healing and are able to continue oral medication and outpatient follow-up. Transfers to other hospitals or rehabilitation institutions, if any, will be recorded separately. For participants discharged earlier than expected, discharge ECG findings and clinical records will be reviewed to ensure complete outcome capture. All randomised participants will be included in the final analysis whenever possible.

Data management

All trial data will be entered into a secure, password-protected electronic database accessible only to authorised study personnel.

Data management procedures include:

1. Double data entry for primary outcome variables.

2. Range checks for continuous variables.

3. Logical consistency checks.

4. Regular electronic data capture system backups.

Each participant will be assigned a unique study identification number. Identifiable information will be stored separately from research data.

Confidentiality

Personal information of potential and enrolled participants will be collected only as required for clinical care and research purposes. All identifiable data will be coded using unique study identification numbers. Access to identifiable information will be restricted to the principal investigator and designated study coordinators. Data will not be disclosed to third parties without written permission from the participant, except as required by regulatory authorities. All study-related documents will be stored in locked cabinets and secure institutional servers. After trial completion, data will be retained according to national regulations and institutional policy.

Statistical methods

Statistical methods for primary and secondary outcomes

All statistical analyses will be performed using R software (V.4.4.2). A two-sided p value <0.05 will be considered statistically significant.

Primary outcome: The primary endpoint (incidence of POAF during hospitalisation) is a binary variable. Group comparisons will be performed using the chi-square test. If the expected frequency in any cell is <5, Fisher’s exact test will be used. RR and 95% CIs will be calculated.

Secondary outcomes: Continuous variables (eg, duration of POAF, ventilation time, LOS). Assessed for normality using Shapiro-Wilk test. Normally distributed data: independent-sample t-test. Non-normally distributed data: Mann-Whitney U test. Categorical variables (eg, reoperation, use of antiarrhythmic drugs, MACCEs). Compared using χ² or Fisher’s exact test.

Safety analysis: All safety endpoints will be compared descriptively between groups.

Who will be included in each analysis

The primary analysis will follow the ITT principle. A per-protocol analysis will be performed as a secondary sensitivity analysis, excluding participants with major protocol violations.

How missing data will be handled in the analysis

Because the primary outcome is assessed during hospitalisation under continuous ECG monitoring, missing data for the primary endpoint are expected to be minimal.

If missing data exceed 5% for secondary outcomes:

1. Multiple imputation using chained equations will be performed.

2. Sensitivity analyses will compare complete-case and imputed analyses.

The extent and reasons for missing data will be reported transparently.

Methods for additional analyses (eg, subgroup analyses)

Prespecified subgroup analyses will be conducted to explore potential effect modification by: age (<65 vs ≥65 years), baseline left atrial diameter and congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischaemic attack/thromboembolism, vascular disease, age 65–74 years and sex category (CHA2DS2-VASc) score. Interaction terms will be tested using logistic regression models.

Adjusted analyses will also be performed using multivariable logistic regression, including clinically relevant covariates such as: age, sex, body mass index, hypertension, diabetes, left atrial diameter. Adjusted ORs with 95% CIs will be reported.

These analyses will be considered exploratory.

Interim analyses

No formal interim analysis is planned. Given that this is a single-centre study with a moderate sample size and a low-risk surgical adjunct procedure, no early stopping rules have been predefined.

Protocol and statistical analysis plan

The full trial protocol will be made publicly available through journal publication. The statistical analysis plan (SAP) is incorporated within this protocol. If further refinement of the SAP is required, an updated version will be finalised prior to database lock and made available as a supplementary file or protocol update. No outcome data will be analysed before database lock.

Oversight and monitoring

Composition of the coordinating centre and trial steering committee

The coordinating centre for this study is located at the cardiac surgery department in Peking University Third Hospital. The coordinating team is responsible for the overall management of the trial, including participant recruitment, data collection, protocol implementation, and regulatory compliance.

A trial steering committee (TSC) composed of senior clinicians and investigators will oversee the scientific integrity and progress of the study. The TSC will review study progress, protocol adherence and safety information.

Outcome adjudication will be performed by independent investigators who are blinded to treatment allocation. In cases of disagreement, a senior cardiologist will provide final adjudication. A dedicated data management team will oversee data entry, data verification and database maintenance. The coordinating team will meet regularly to review trial progress and operational issues.

Composition of the data monitoring committee, its role and reporting structure

Given the single-centre design, moderate sample size and low-risk nature of the intervention, a formal independent Data Monitoring Committee has not been established. Trial safety and conduct will instead be monitored by the principal investigator and the TSC. SAEs will be reported to the institutional ethics committee in accordance with regulatory requirements.

Frequency and plans for auditing trial conduct

The conduct of the trial will be monitored internally by the study coordinating team.

Periodic reviews will be conducted to ensure:

1. Protocol adherence.

2. Accuracy of data collection.

3. Completeness of CRFs.

Audits may be performed by the institutional ethics committee if required. No external independent audit is currently planned.

Protocol amendments

Any important modifications to the study protocol (eg, changes to eligibility criteria, outcomes or analyses) will be submitted to the institutional ethics committee for approval prior to implementation. Approved amendments will also be updated in the trial registry. Investigators and relevant study personnel will be informed of protocol changes through formal communication.

Dissemination policy

The results of this trial will be disseminated through publication in peer-reviewed scientific journals and presentations at national and international conferences. The trial results will also be updated in the clinical trial registry in accordance with reporting requirements. Authorship will follow the recommendations of the International Committee of Medical Journal Editors. Participants will be able to access the published results on request.

Discussion

POAF is one of the most common complications after CABG and is associated with increased morbidity, prolonged hospitalisation and higher healthcare costs. Despite advances in perioperative management, the incidence of POAF remains substantial.

The LOM has been recognised as an important structure involved in the pathogenesis of AF due to its autonomic innervation and potential arrhythmogenic activity. Previous electrophysiological and surgical studies have suggested that modification of the LOM may reduce atrial arrhythmia susceptibility. However, high-quality randomised clinical evidence evaluating the preventive effect of LOM resection during CABG is still limited. The intervention evaluated in this trial differs from previous partial cardiac denervation strategies. In the partial cardiac autonomic denervation for postoperative atrial fibrillation trial, partial cardiac denervation was achieved by cutting off the LOM and resecting the fat pad along the Waterston groove. By contrast, LOMEX-AF is designed to assess isolated LOM excision without concomitant Waterston groove fat pad resection. This focused approach may help clarify the specific contribution of the LOM to POAF prevention in the surgical setting. In addition, avoiding manipulation of the Waterston groove fat pad simplifies the operative procedure, improves reproducibility and may enhance safety in minimally invasive CABG.

This trial aims to evaluate whether excision of the LOM during MICS-CABG can reduce the incidence of POAF. The randomised design and blinded outcome assessment are intended to minimise bias and provide reliable evidence regarding the effectiveness and safety of this surgical adjunct.

Several practical considerations arise in the conduct of this study. First, because the intervention is performed during cardiac surgery, the operating surgeon cannot be blinded to treatment allocation. To mitigate potential bias, outcome assessment and statistical analysis will be performed by investigators blinded to group allocation. Second, as the primary outcome is assessed during hospitalisation using continuous ECG monitoring, the risk of loss to follow-up is minimal. Third, as this is a single-centre study, the generalisability of the findings to other surgical centres with different patient populations, perioperative care pathways or levels of experience in MICS-CABG may be limited. However, the single-centre setting also allows for consistency in surgical technique, perioperative management and postoperative rhythm monitoring.

The results of this study may provide prospective clinical evidence regarding the efficacy and safety of isolated LOM excision for preventing POAF during MICS-CABG. These findings may contribute to optimising surgical strategies for arrhythmia prevention in cardiac surgery and inform the design of future multicentre studies.

Ethics and dissemination

The study has been approved by the institutional ethics committee of Peking University Third Hospital, Beijing, China (IRB00006761-M20250847; 11 October 2025). The trial will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice principles and all applicable national regulations. Any important protocol amendments will be submitted to the ethics committee for review and approval before implementation.

Written informed consent will be obtained from all participants by trained research staff before enrolment. Participants will be given sufficient time to read the informed consent form, ask questions and discuss participation with their family members or other trusted individuals before making a decision. Participation in the study is voluntary, and participants may withdraw from the study at any time without giving a reason and without any effect on their standard medical care, legal rights or entitled benefits. A sample participant informed consent form is provided as online supplemental file.

Participant confidentiality will be strictly protected. Each participant will be assigned a unique study identification number, and identifiable personal information will be stored separately from study data. Access to identifiable information will be restricted to authorised research personnel. Study data will be stored securely in the Department of Cardiac Surgery, Peking University Third Hospital, and will be used only for purposes related to this study. When the study findings are presented or published, no information that could identify individual participants will be disclosed.

AEs and SAEs will be monitored throughout the perioperative period and managed promptly according to standard clinical practice. Any confirmed study-related injury will be treated in accordance with institutional policies and applicable laws and regulations. The results of this trial will be disseminated through publication in peer-reviewed journals and presentations at national or international academic conferences. The findings will also be used to inform future research on the prevention of POAF after minimally invasive CABG.

Trial status

This trial has been registered in the Chinese Clinical Trial Registry (ChiCTR). Patient recruitment began on 24 October 2025.

At the time of manuscript submission, more than 190 participants have been enrolled, and recruitment is ongoing.

Participant enrolment is expected to be completed in approximately January 2027.

The current protocol version is Version 1.0, dated 12 September 2025.

Although several authors are affiliated with Peking University Third Hospital, the funder had no role in the study design; collection, management, analysis or interpretation of data; writing of the manuscript; or the decision to submit the manuscript for publication. The funder did not influence the content of the manuscript and will not influence the conduct, analysis or reporting of the trial.