Prediction Model for MINS After Major Hepatobiliary Surgery

Development of an Interpretable Prediction Model for Myocardial Injury After Noncardiac Surgery in Patients Undergoing Major Hepatobiliary Surgery

This multi-center, prospective observational study aims to develop and validate an interpretable prediction model for Myocardial Injury After Noncardiac Surgery (MINS) in patients undergoing major hepatobiliary surgery. The study adopts a nested modeling strategy, starting with baseline risk factors (e.g., RCRI) and stepwise incorporating hepatic inflow occlusion strategies (specifically comparing SPVO vs. Pringle maneuver) and routine intraoperative biomarkers. The model's performance will be evaluated using AUC, Net Reclassification Improvement (NRI), and Decision Curve Analysis (DCA), followed by interpretability analysis using SHAP values and external validation in an independent cohort.

Study Overview

• Status: Recruiting
• Conditions: Postoperative Complications; Liver Neoplasm; Hepatobiliary Diseases; Myocardial Injury After Noncardiac Surgery (MINS)
• Intervention / Treatment: Procedure: Major Hepatobiliary Surgery

Detailed Description

Study Design and Methodology: The study consists of four consecutive phases aimed at constructing a robust and interpretable prediction model for MINS.

1. Multi-center Cohort Standardization: Based on clinical data from multiple participating centers, the investigators will establish a standardized structural dataset. Strict inclusion and exclusion criteria will be applied. The process involves rigorous data cleaning and normalization to harmonize demographics, surgical operation details, and perioperative hemodynamic parameters across different centers, laying the foundation for model construction.

2. Nested Modeling and Performance Evaluation: A nested modeling strategy will be employed to assess the incremental predictive value of specific surgical and biological variables:

   Model A (Baseline): Constructed using standard baseline variables such as the Revised Cardiac Risk Index (RCRI).

   Model B (+Surgical Technique): Incorporates hepatic inflow occlusion strategies, specifically comparing SPVO (Selective Pringle Vascular Occlusion) vs. Pringle maneuver, along with occlusion duration and frequency.

   Model C (Full Model): Further incorporates MINS-related biomarkers.

   Model performance will be comprehensively evaluated using:

   Discrimination: Area Under the Receiver Operating Characteristic Curve (AUC).

   Calibration: Calibration plots.

   Clinical Utility: Net Reclassification Improvement (NRI) and Decision Curve Analysis (DCA) to assess the improvement in risk stratification and clinical net benefit after adding new variables.

3. Model Interpretability Analysis: To enhance the transparency of the model ("White-box" approach), SHAP (SHapley Additive exPlanations) values or similar methods will be utilized. This will quantify and visualize the specific contribution (weight) of key variables, such as SPVO usage, to the individual risk prediction, aligning the statistical results with clinical medical reasoning.
4. External Validation: The final model will undergo validation using an independent external clinical cohort. This step aims to test the stability and generalizability of the model across different center data, defining its applicable scope in real-world clinical scenarios.

• Study Type: Observational
• Enrollment (Estimated): 1800

Contacts and Locations

• Study Contact: Name: Zhifeng Gao, MD; Phone Number: +86-15801249466; Email: gzfa02461@btch.edu.cn

Study Locations

• China
  • Beijing, China
    • Not yet recruiting
    • Peking University International Hospital
    • Contact: Lin Ding, MD; Phone Number: +86-13269092835; Email: 13269092835@163.com
  • Beijing, China
    • Recruiting
    • Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine，Tsinghua University
    • Contact: Zhifeng Gao, MD; Phone Number: +86-15801249466; Email: gzfa02461@btch.edu.cn
  • Chongqing, China
    • Not yet recruiting
    • The First Affiliated Hospital of Army Medical University
    • Contact: Zhiyu Chen, MD; Phone Number: +86-13983881219; Email: chenzhiyu_umn@163.com
    • Contact: Zhifeng Gao, MD; Email: gzfa02461@btch.edu.cn
  • Qingdao, China
    • Not yet recruiting
    • Qingdao West Coast New Area People's Hospital
    • Contact: peng Zhang, MD; Phone Number: +86-16678658917; Email: zhangpeng27309@126.com
  • Shandong, China
    • Not yet recruiting
    • The First Affiliated Hospital of Shandong First Medical University
    • Contact: Ming Hou, MD; Phone Number: +86-13869183831; Email: 13869183831@126.com
  • Zhuhai, China
    • Not yet recruiting
    • Zhuhai People's Hospital
    • Contact: Wenpeng Li, MD; Phone Number: +86-13431577611; Email: liwenpeng324324@163.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

1800

Description

Inclusion Criteria:

Adults (18-85 yr, ASA physical status II-III) undergoing major hepatobiliary surgery were enrolled. Major surgery was defined as duration ≥ 3 h involving hepatectomy (≥ 3 segments) or biliary reconstruction necessitating ICU admission. Eligibility required paired perioperative high-sensitivity cardiac troponin T (hs-cTnT) data and comprehensive documentation of surgical covariates, including surgical approach (laparoscopic vs. open), resection nature (anatomic vs. non-anatomic), number of resected segments, tumor characteristics (size and location), and presence of cirrhosis.

Exclusion Criteria:

(1) preoperative acute myocardial infarction, unstable angina, heart failure, or chronic kidney disease (estimated glomerular filtration rate < 60 ml/ (min · 1.73 m2); (2) undocumented inflow occlusion strategy; or (3) non-imputable missing covariates.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study Cohort; Adult patients scheduled for major hepatobiliary surgery at Beijing Tsinghua Chang Gung Hospital and other participating centers.	Procedure: Major Hepatobiliary Surgery; Patients undergo standard major hepatobiliary surgery (e.g., hepatectomy). The specific surgical strategy, including the method of hepatic inflow occlusion (e.g., Pringle maneuver or SPVO), is determined by the attending surgeon based on routine clinical practice and patient condition, not by the study protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Myocardial Injury After Noncardiac Surgery	MINS is defined as myocardial injury resulting from myocardial ischemia (that may or may not result in necrosis) occurring within 30 days after surgery. The diagnosis is based on a peak high-sensitivity cardiac troponin (hs-cTn) level exceeding the 99th percentile upper reference limit (URL) due to presumed ischemic etiology, irrespective of the presence of ischemic symptoms or electrocardiographic (ECG) changes. Routine hs-cTn screening will be performed on postoperative days 1, 2, and 3. Additional measurements will be taken if clinical signs of ischemia occur anytime within the 30-day follow-up period.	Within 30 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day All-cause Mortality	Death from any cause postoperatively.	Within 30 days after surgery
Postoperative Length of Hospital Stay	Duration from surgery to hospital discharge.	Up to 90 days

Collaborators and Investigators

• Sponsor: Beijing Tsinghua Chang Gung Hospital
• Investigators: Principal Investigator: Zhifeng Gao, MD, Beijing Tsinghua Changgeng Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: January 4, 2026
• First Submitted That Met QC Criteria: January 4, 2026
• First Posted (Estimated): January 12, 2026

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 4, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Hepatectomy; Prediction Model; MINS; High-sensitivity Cardiac Troponin; Major Hepatobiliary Surgery; Hepatic Inflow Occlusion; Pringle Maneuver
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Liver Diseases; Pathological Conditions, Signs and Symptoms; Digestive System Diseases; Liver Neoplasms; Postoperative Complications
• Other Study ID Numbers: 25454-4-01-01

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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