High-Sensitivity Troponin I After Cardiac Surgery and 30-Day Mortality

Mar 03, 2022
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Authors:
Devereaux PJ, Lamy A, Chan MT, et al., on behalf of the VISION Cardiac Surgery Investigators.
Citation:
High-Sensitivity Troponin I After Cardiac Surgery and 30-Day Mortality. N Engl J Med 2022;386:827-836.
Summary By:
Rachel Eshima McKay, MD

Quick Takes

  • Recent consensus statements have identified prognostically significant high-sensitivity troponin I (hs-cTnI) elevation thresholds after cardiac surgery, ranging from >10 to ≥70 times the upper reference limit (URL), but these thresholds have not been proven with robust evidence.
  • In a very large cohort of adult cardiac surgery patients receiving a standardized monitoring protocol, peak hs-cTnI values associated with increased risk of 30-day postoperative mortality were markedly higher than the thresholds defining postoperative MI or clinically significant myocardial injury in recent consensus guidelines.
  • In all, 75% of patients undergoing major cardiac surgery had peak hs-cTn values exceeding 70× URL.
  • A greater risk of 30-day mortality was observed if hs-cTnI was >218× higher than the URL after isolated CABG or aortic valve replacement, or >499× higher than URL after other cardiac surgical procedures.

Study Questions:

In patients undergoing cardiac surgery, what postoperative threshold high-sensitivity cardiac troponin I (hs-cTnI) elevation is associated with increased risk of 30-day postoperative mortality?

Methods:

Patients aged ≥18 years undergoing cardiac surgery at 24 hospitals in 12 countries between May 2013–April 2019 were enrolled in the VISION (Vascular Events in Surgery Patients Cohort Evaluation) Cardiac Surgery Trial. Hs-cTnI levels were measured using ARCHITECT STAT assay (Abbott Laboratories), with upper reference limit (URL) of 26 ng/L to determine threshold postoperative enzyme elevation levels predictive of postoperative mortality. Exclusion criteria included preoperative myocardial infarction (MI), preoperative hs-cTnI concentration ≥300 ng/L, or less complex surgery (pericardial window, pericardiectomy, or cardiac implantable electronic device implantation). Hs-cTnI was measured 3-12 hours and 1, 2, and 3 days after surgery, and both clinicians and investigators were blinded to these assay results.

The primary outcome was death within 30 days of surgery, and secondary outcome was a composite of vascular complications (nonfatal MI 4-30 days after surgery or insertion of a mechanical circulatory support device within 30 days of surgery). The Cox regression was adjusted using the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), a validated 18-item risk stratification tool that identifies comorbidity and procedural factors known to impact the risk of in-hospital mortality after cardiac surgery.

Results:

A total of 13,862 patients were included in the analysis, 70.9% of whom were male, with mean age of 63.3 years and 29.3% incidence of previous MI. The primary outcome (30-day mortality) occurred in 2.1%, and secondary outcome (major vascular complications) occurred in 2.9% of subjects. Preoperative median (interquartile range [IQR]) hs-cTnI was 9 (4, 20) ng/L. Peak postoperative hs-cTnI median (IQR) was 3920 (1799, 8734) ng/L.

In the adjusted model, an increased hazard of 30-day mortality was associated with every 1-unit increase in the natural log of the peak troponin elevation:

  • Adjusted hazard ratio (aHR) = 1.62 (1.36, 1.93) on postoperative day (POD) 1 after coronary artery bypass grafting (CABG) or aortic valve repair or replacement (AVR)
  • aHR = 1.84 (1.41, 2.40) on POD 2-3 after CABG or AVR
  • aHR = 1.75 (1.48, 2.07) on POD 1 after other/combined cardiac surgery
  • aHR = 2.77 (2.19, 3.51) on POD 2-3 after other/combined cardiac surgery

The lowest (threshold) hs-cTnI (ng/L) values associated with aHR >1.00 for 30-day postoperative mortality were as follows:

  • 5670 ng/L (95% confidence interval [CI] 1075, 8260) on POD 1 (218× URL) after CABG or AVR
  • 1522 ng/L (95% CI 1325, 2433) on POD 2-3 (59× URL) after CABG or AVR
  • 12,981 ng/L (95% CI 2673, 16,591) on POD 1 (499× URL) after other/combined cardiac surgery
  • 2503 ng/L (95% CI 1228, 4033) on POD 2-3 (96× URL) after other/combined cardiac surgery

The lowest hs-cTnI (ng/L) values associated with aHR >1.00 for 30-day postoperative vascular complications were as follows:

  • 4184 ng/L (95% CI 1488, 7781) on POD 1 (161× URL), and 1099 ng/L (95% CI 310, 1972) on POD 2-3 (42× URL) after isolated CABG or AVR
  • 9654 ng/L (5227, 15,107) on POD 1 (371× URL), and 1888 ng/L (95% CI 1495, 2989) on POD 2-3 (73× URL) after other or combined cardiac surgery

Conclusions:

Threshold hs-cTnI associated with increased risk of 30-day mortality was 218× URL among patients undergoing isolated CABG and AVR, and 499× URL on POD 1 among patients undergoing other or combined major cardiac surgical procedures. These postoperative hs-cTnI thresholds are 3-7 times greater in magnitude than previously defined thresholds cited as clinically significant indicators of postoperative MI or myocardial injury in recent consensus statements.

Perspective:

High-sensitivity troponin thresholds predicting greater risk of 30-day mortality in this cohort of cardiac surgery patients were markedly higher than those cited in recent consensus documents that, by convention, define MI or clinically important postoperative myocardial injury. The apparent discrepancy between these results, compared to previous investigations showing associations between more modest troponin elevation thresholds and adverse postoperative outcomes, may relate to differences between specific assays chosen, or to the fact that new-onset ischemia, defined by criteria distinct from biomarker elevation, was not included as an outcome in the analysis. These findings underscore the limitations of a highly sensitive biomarker to distinguish between clinically significant postoperative myocardial injury warranting intervention versus enzyme release caused by events that took place during the surgical procedure.

Clinical Topics: Cardiac Surgery, Cardiovascular Care Team, Invasive Cardiovascular Angiography and Intervention

Keywords: Biomarkers, Cardiac Surgical Procedures, Cardiology Interventions, Comorbidity, Coronary Artery Bypass, Hospital Mortality, Myocardial Infarction, Postoperative Complications, Risk Assessment, Transcatheter Aortic Valve Replacement, Troponin I


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