Submaximal Cardiopulmonary Exercise Testing for Detection of Myocardial Injury After Noncardiac Surgery (EnhanceMINS)

Enhancing Precise Perioperative Risk Surveillance: Validation of Submaximal Cardiopulmonary Exercise Testing to Usual Care for Detection of Myocardial Injury After Noncardiac Surgery

The goal of this clinical trial is to learn whether physicians can associate evidence of myocardial injury after surgery with findings obtained from submaximal cardiopulmonary exercise testing. The main questions are:

Is detection of postoperative myocardial injury with submaximal cardiopulmonary exercise testing superior to using usual care?

And which submaximal cardiopulmonary exercise testing measure is better?

Participants will undergo evaluation with a short submaximal cardiopulmonary exercise test, then undergo surgery. Myocardial injury will be measured on postoperative days 0, 1, 2, and 3 (during and up to 3 days after surgery). These results will analyzed by comparing it to findings from the submaximal cardiopulmonary exercise test.

If there is a relationship, this will help anesthesiologists and surgeons assign certain treatments that may reduce the risk of developing myocardial injury after surgery.

Study Overview

• Status: Terminated
• Conditions: Preoperative Period; Submaximal Exercise Performance; Myocardial Injury After Non-cardiac Surgery
• Intervention / Treatment: Diagnostic test: High-sensitivity troponin, serum; Diagnostic test: Submaximal Cardiopulmonary Exercise Testing; Diagnostic test: Duke Activity Status Index

Detailed Description

Among the 50 million US adults undergo non-cardiac surgery each year, an estimated 1.4-3.9% of patients experience perioperative myocardial infarction with another 6-18% showing evidence of myocardial injury. These cardiac insults, known as myocardial injury after noncardiac surgery (MINS) are associated with a 2.7-3.2 fold higher odds of 30-day mortality, 2.2 fold higher odds of nonfatal myocardial infarction (MI), 1.55 fold increase in 30-day congestive heart failure events, and 5.2 times higher risk of stroke, highlighting the importance of predicting and treating their occurrence. MINS is treatable, and potentially preventable, by a combination of tailored intraoperative monitoring and appropriate post-operative care.

The current approach to preoperative risk stratification is predominately derived from patient-reported functional capacity associated with history, physical examination and select laboratory investigations. This approach results in significant healthcare worker time and cost expenditures, without improved perioperative outcomes. In contrast, a technological approach utilizing conventional cardiopulmonary exercise testing (CPET) has been shown to improve individualized identification of high-risk patients prior to surgery. Widespread cardiopulmonary exercise test adoption in the perioperative setting, however, has been limited by cost, technical requirements, and time investment despite its documented utility in cardiopulmonary risk assessment. However, brief submaximal cardiopulmonary exercise testing (smCPET) addresses the limitations of conventional CPET including low cost, low time investment, small footprint, and ease of operator efficiency. In our pilot (under review), we demonstrated the feasibility and performance of implementing smCPET within a high-volume pre-surgical evaluation clinic.

This proposal seeks to continue work in characterizing smCPET and its role in individualized preoperative risk identification. The aim of this study proposal is to validate two clinically relevant questions: 1) Are smCPET measures superior to usual care (Duke Activity Status Index) in patients undergoing moderate to high-risk noncardiac surgery and 2) to determine which smCPET measure is more sensitive to MINS as described by abnormalities in postoperative high-sensitivity troponin measurements.

Using a smCPET-guided approach, this study seeks to characterize its value in identifying high-risk patients for MINS, provide further validation of smCPET utility as a preoperative risk stratification approach, and preliminarily identify smCPET measures with highest association with MINS.

If validated, this would provide the foundation for a smCPET-guided clinical decision support system of preoperative identification and perioperative monitoring that could 1) enhance patient outcomes by providing early prediction and detection of MINS and 2) characterize a research methodology to stratify participants for further research in assessing perioperative strategies to reduce MINS. These findings will provide one of the first examples of quantitative and individualized preoperative risk identification methods for a common and deleterious perioperative outcome.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University; Yale New Haven Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Provision of signed and dated informed consent form.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Biological male or female, aged 45 years or older.
4. In good general health as evidenced by medical history or diagnosed with metabolic equivalents (self-reported ability to climb 1 flight of stairs).
5. Revised Cardiac Risk Index less than or equal to three.
6. Willing to accept phlebotomy on operative day 0, 1, 2, and 3, as part of usual care.
7. Scheduled for moderate to high-risk elective non-cardiac surgery with an expected 24-72 hour stay within 60 days of enrollment in the study.

Exclusion Criteria:

1. Inability to perform study procedures as defined by inability to achieve greater than 4 metabolic equivalents (cannot climb 1 flight of stairs reliably).
2. Pregnancy or lactation.
3. Inability to give independent informed consent.
4. Revised cardiac risk index greater than 3.
5. Recent myocardial infarction (less than 6 weeks).
6. Recent anginal symptoms (stable or unstable) within past 6 months.
7. Recent admission or endorsement for congestive heart failure within 6 months
8. Recent admission or endorsement for syncope within 6 months.
9. Symptomatic tachy- or bradyarrhythmia (supraventricular tachcardia, ventricular tachycardia with symptoms of intermittent dizziness, pre- syncopal events)
10. Uncorrected severe valvular heart disease (severe aortic, tricuspid or mitral stenosis)
11. Acute pulmonary embolism or deep vein thrombosis (within past 6 months)
12. Uncontrolled pulmonary edema
13. Uncontrolled symptomatic cardiac arrhythmias.
14. Active endocarditis
15. Active myocarditis or pericarditis
16. Active wheezing or recent exacerbation of chronic obstructive pulmonary disease admission in past 6 months.
17. Inability to perform components of the SHAPE test (severe hip flexion limitation, severe osteoarthritis of knee or hip, limb immobilization, ambulation requires cane or crutches, baseline balance irregularities.
18. Diagnosis of symptomatic vertigo
19. Known allergic reactions to components of the SHAPE medical system apparatus disposable mouthpiece.
20. Active enrollment in an interventional clinical trial within the enrollment period of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Submaximal cardiopulmonary exercise testing; Single arm design; selected participants will receive both usual care (Duke Activity Status Index) and submaximal cardiopulmonary exercise testing. All participants will receive high-sensitivity troponin measurements on operative day 1 and postoperative day 1,2,3

Diagnostic test: High-sensitivity troponin, serum; A serum derived measure of myocardial injury. Threshold value of 14ng/L.; Other Names: HST; Diagnostic test: Submaximal Cardiopulmonary Exercise Testing; FDA-approved device uses breath by breath sampling during calibration and exercise challenge. Analysis is performed using a differential pressure pneumotach method for volume calibration and measurement, an infrared sensor for CO2 and a paramagnetic sensor for O2 measurements. Automated calibration using a calibration gas mixture (15.6% O2/5% CO2) is performed at regular intervals. The Shape II calculations used to differentiate causes of exertional dyspnea are Artificial Intelligence (AI) based algorithms and measurements have been previously validated to conventional cardiopulmonary exercise testing methods. Brief smCPET is comprised of a 2-minute calibration phase, 3 minutes of graded exercise using a stair-step and a 1 minute recovery phase for a total of 6 minutes. An instant report is then generated.; Other Names: smCPET; Diagnostic test: Duke Activity Status Index; A validated measure of preoperative functional capacity which will be utilized to cross-validate smCPET peak VO2. Low DASI score has been found to estimate peak oxygen uptake (VO2), predict MINS, myocardial infarction, and inducible myocardial ischemia on myocardial perfusion scintigraphy.; Other Names: DASI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MINS	Myocardial Injury after noncardiac surgery. Measurement: High-Sensitivity Troponin assay with an abnormal value defined as 14 nanograms per liter or greater.	Operative Day 0, Postoperative Day 1, 2 or 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day Major Adverse Cardiovascular Events	30-day recorded events of atrial fibrillation, angina, stroke, myocardial infarction, congestive heart failure as defined by International Classification of Disease (Version 10) coding.	Postoperative Day 1 through Postoperative Day 30
Length of Stay	Measurement of patient inpatient status from operative day 0 through physical discharge from the hospital.	From operative day 0 through hospital discharge up to postoperative day 180
Readmission	Readmission of any type from the time of surgical procedure discharge through postoperative day 60.	Postoperative Day One through Postoperative Day 60.

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Zyad J Carr, M.D., Yale University

Publications and helpful links

General Publications

• Snowden CP, Prentis JM, Anderson HL, Roberts DR, Randles D, Renton M, Manas DM. Submaximal cardiopulmonary exercise testing predicts complications and hospital length of stay in patients undergoing major elective surgery. Ann Surg. 2010 Mar;251(3):535-41. doi: 10.1097/SLA.0b013e3181cf811d.
• Devereaux PJ, Goldman L, Cook DJ, Gilbert K, Leslie K, Guyatt GH. Perioperative cardiac events in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk. CMAJ. 2005 Sep 13;173(6):627-34. doi: 10.1503/cmaj.050011.
• Le Manach Y, Perel A, Coriat P, Godet G, Bertrand M, Riou B. Early and delayed myocardial infarction after abdominal aortic surgery. Anesthesiology. 2005 May;102(5):885-91. doi: 10.1097/00000542-200505000-00004.
• Patel AY, Eagle KA, Vaishnava P. Cardiac risk of noncardiac surgery. J Am Coll Cardiol. 2015 Nov 10;66(19):2140-2148. doi: 10.1016/j.jacc.2015.09.026.

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2025
• Primary Completion (Actual): April 30, 2026
• Study Completion (Actual): April 30, 2026

Study Registration Dates

• First Submitted: June 14, 2024
• First Submitted That Met QC Criteria: June 24, 2024
• First Posted (Actual): June 26, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: anesthesiology; MINS; perioperative myocardial injury; submaximal cardiopulmonary exercise testing; myocardial injury after noncardiac surgery
• Additional Relevant MeSH Terms: Wounds and Injuries
• Other Study ID Numbers: 2000037991

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study protocol, statistical analysis plan, informed consent and human study record will be provided. A deidentified dataset will be uploaded to the data sharing repository NIBIB physionet website.
• IPD Sharing Time Frame: For 24 months after initial study publication.
• IPD Sharing Access Criteria: CITI trained certified individuals that meet criteria set forth by physionet.org.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes