Myocardial injury after Noncardiac Surgery. A large, international, Prospective Cohort Study Establishing Diagnostic Criteria, Characteristics, Predictors and 30-day Outcomes

Anesthesiology 2014; 120:564-78

Presented by Dr S. Tufail

 Background

  • Most studies focus on perioperative myocardial INFARCTION
  • Patients sustain myocardial injury in the perioperative period which will not satisfy criteria for myocardial infarction
  • These patients have a poor prognosis
  • Timely & appropriate intervention could potentially improve outcome
  • Proposed definition of myocardial injury after non-cardiac surgery (MINS)
    • Myocardial injury caused by ischaemic (that may or may not result in necrosis), has prognostic relevance and occurs during or within 30 days after non-cardiac surgery.
    • Does not include injury due to non-ischaemic etiology

 Primary Objective:

  • Inform the diagnostic criteria of MINS

Secondary Objectives:

  • Determine characteristics, predictors & 30 day outcomes of MINS

 Design and Setting

  • Used VISION data
  • VISION: The Vascular events In noncardiac Surgery patIents cOhort evaluatioN
    • Large (ongoing) international prospective cohort study
  • Evaluating complications post non cardiac surgery
  • Previous publication showed Troponin in the first 3 days after surgery were independent predictors of 30 day mortality

MINS Study

  • Analyzed VISION data
  • Evaluated troponin elevations until day 30 after surgery
  • Excluded non-ischemic troponin elevations
  • Adjusted for perioperative complications
  • VISION: First 15,000 patients had event rates three times higher than expected. Had enough data for MINS objectives

 Subjects

  • Eligible patients for VISION study:
    • Non cardiac surgery
    • Aged 45 years or older
    • General or regional anaesthesia
    • Elective or urgent/emergency surgery
    • Day or night
    • Weekday/weekend
    • 15,065 patients

 Intervention

  • Patients interviewed, examined & charts reviewed for potential pre-operative predictors of major perioperative complications
  • 4th generation Troponin T (TnT)
    • 6-12 hours post op
    • 1st day, 2nd day & 3rd day
  • TnT 0.04ng/ml or greater, lab threshold for abnormal at time study began
  • If TnT greater than/equal to 0.04ng/ml, assessed patients for ischemic symptoms & ECG
  • If patients developed ischemic symptoms during first 30 days, physicians encouraged to obtain TnT & ECG.

Outcomes

  • Primary Outcome:
    • Mortality at 30 days post op (Cause of death also reported
  • Secondary Outcomes:
    • Patients evaluated throughout hospital stay by research staff
    • Contacted patients 30 days post op-if patient or NOK indicated an event, patient’s notes were reviewed

Adjudicators:

  • Evaluated all patients with an elevated TnT (1st 30 days)
  • Presence of any ischemic features (? Myocardial infarction)
  • ? Non ischemic reason for raised TnT
  • Check myocardial injury occurred during or after surgery (ie. Not pre-op)
  • Their decisions used in statistical analysis

Statistical Analysis

  • Primary objective: MINS diagnostic criteria
  • Cox proportional hazards model
  • Dependent variable: Death up to 30 days after non-cardiac surgery
  • Independent variables
    • 9 pre-op characteristics (VISION stats)
    • 6 time-dependent perioperative adverse complications
    • Potential MINS diagnostic criteria

Potential MINS diagnostic criteria

  • Peak TnT ≥ 0.04ng/ml with one or more ischemic feature
    • If this- repeat analysis with exploration of impact of each individual ischemic feature on 30 day mortality to decide which to include in MINS diagnostic criteria
  • Peak TnT ≥ 0.04ng/ml without an ischemic feature
    • If this- planned to repeat MINS diagnostic criteria COX proportional hazard model with two more diagnostic criteria
    • TnT 0.02ng/ml & TnT 0.03ng/ml, without knowledge of ischemic features.
    • Reference group (TnT ≤ 0.01ng/ml)
  • After establishing MINS diagnostic criteria, determined the incidence & 95% CI of patients fulfilling these criteria
  • Patients who developed MINS determine incidence of each individual ischemic feature
  • Compared cardiovascular outcomes at 30 days for patients who did and did not suffer MINS (Fischer exact test)

Sample Size

  • Model to determine diagnostic criteria of MINS
  • Evaluated 19 variables
  • Required 228 deaths in the study

Results

  • Model to determine diagnostic criteria of MINS
  • Evaluated 19 variables
  • Required 228 deaths in the study
  • TnT ≥ 0.04ng/ml with one or more ischemic feature
  • TnT ≥ 0.04ng/ml with no ischemic feature
  • TnT ≥ 0.03ng/ml

ALL independently predicted 30 day mortality

  • Diagnostic criteria for MINS (Primary objective):
    • Any peak TnT of ≥ 0.03ng/ml that was judged as resulting from myocardial ischaemia
  • Total of 1200 patients (8%, 95% CI 7.5-8.4) fulfilled the MINS criteria
  • 1% of MINS events occurred within the first two days after surgery
  • 2% of patients suffering MINS did NOT experience ischemic symptoms
  • 9% with MINS did not have an ischemic ECG
  • 8% would have fulfilled definition of myocardial infarction
  • 12 independent predictors of MINS

Prognostic impact of MINS:

  • Increased risk of non-fatal cardiac arrest, heart failure and stroke
  • 30 day mortality rate:
    • 8% in patients who suffered MINS
    • 1% no MINS (OR 10.07; P<0.001)

Predictors of mortality among patients suffering MINS

  • Age ≥75 years
  • ST elevation/new LBBB
  • Anterior ischemic ECG

Discussion

  • MINS diagnostic criteria established
  • MINS was common (8%)
  • Associated with substantial mortality & CVS complications at 30 days
  • Populations-attributable risk suggests MINS explains 34% of deaths that occur during the first 30 days post op
  • 1 in 10 patients with MINS died within 30 days

Strengths

  • Large study
  • Prospective
  • Good follow up ( 99.7%)
  • Same Troponin assay

Weaknesses

  • Only measured TnT until day 3
  • Can only apply TnT threshold for that one assay
  • Did not assess for ischemic features with TnT 0.03ng/ml
  • May have missed non-ischemic reasons for raised TnT
  • A LOT of stats

Implications

  • Should we assess patients for MINS post op?
  • No established effective treatment
  • However, prognosis may be modifiable e.g. aspirin & statins
  • Need for clinical trials to establish strategies to prevent and treat MINS
  • Majority of MINS would go undetected without TnT measurement post op

Potential for Impact

  • ? Ensure modifiable CVS risk factors optimised pre-op
  • ? Increased vigilance in high risk patients
  • Realistically not going to routinely measure TnT post op in all patients
  • Should TnT be added to blood post op if being done anyway?