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

NCT ID: NCT06474754

Last Updated: 2025-05-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-30
• Study Completion Date: 2026-01-31

Brief Summary

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.

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.

Conditions

Myocardial Injury After Non-cardiac Surgery; Submaximal Exercise Performance; Preoperative Period

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

High-sensitivity troponin, serum

Intervention Type: DIAGNOSTIC_TEST

A serum derived measure of myocardial injury. Threshold value of 14ng/L.

Submaximal Cardiopulmonary Exercise Testing

Intervention Type: DIAGNOSTIC_TEST

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.

Duke Activity Status Index

Intervention Type: DIAGNOSTIC_TEST

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.

Interventions

High-sensitivity troponin, serum

A serum derived measure of myocardial injury. Threshold value of 14ng/L.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

HST; smCPET; DASI

Eligibility Criteria

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.

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zyad J Carr, M.D.

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale University; Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Zyad J Carr, M.D.

Role: CONTACT

zyad.carr@yale.edu

203-785-3689

References

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.

Reference Type: BACKGROUND

PMID: 20134313 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15851872 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16157727 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26541926 (View on PubMed)

Other Identifiers

2000037991

Identifier Type: -

Identifier Source: org_study_id