Perioperative Myocardial Ischemia: Troponin Monitoring,Cost-effectiveness, Insights Into Pathophysiology
Condition: Myocardial Ischemia; Myocardial Injury; Morality
MeSH terms: Myocardial Ischemia; Coronary Artery Disease; Ischemia
Study type: Observational [Patient Registry]

Summary: 
      Background: Despite preoperative screening, technical improvements and increased patient
      monitoring, perioperative myocardial infarction (PMI) remains the first cause of morbidity
      and mortality within 30 days after surgery. Moreover, the available evidence indicates
      worrying rise of risk in postoperative patients with only elevated troponins reflecting
      cardiac injury, but without a conventional clinical diagnosis of myocardial infarction
      according to current definition. Worldwide, annually approximately 300 million adults undergo
      major non cardiac surgery and 10 million of them are estimated to suffer a myocardial injury
      after non-cardiac surgery (MINS), defined as a prognostically relevant increase of a troponin
      T peak of 0.03 ng/ml or greater. Many of the patients with MINS does not fulfill the
      universal definition of myocardial infarction, rarely experience ischemic symptoms and their
      prognosis is very poor (1 out of 10 die at 30 days).Troponin levels needed to be monitored in
      order to MINS diagnose and high sensitive cardiac troponin T assays are currently the most
      frequently used.

      Methods: Patients with high cardiovascular risk undergoing major non-cardiac surgery will be
      selected from the daily surgical program during a two years period Three determinations of
      hs-cTnT for each patient will be obtained. The proportion of patients with MINS and pre- and
      post-operative thresholds of hs-cTnT that would be prognostically relevant will be
      determined. The cost-effectiveness analysis of hs-cTnT monitoring compared with usual care
      will be undertaken. Finally using computed tomography angiography (CTA) and cardiac magnetic
      resonance imaging (MRI) pathophysiology of MINS will be determined, whether is due to plaque
      rupture, supply-demand mismatch, non-ischemic cardiac cause or non-cardiac cause.

      Discussion: The study will evaluate the feasibility and impact of implementing the hs-cTnT
      monitoring program in the Hospital de la Santa Creu i Sant Pau of Barcelona, as well as its
      cost-effectiveness. Moreover, this is the first study which will determine pre and
      postoperative thresholds of hs-cTnT and with minimally invasive diagnostic tools will
      evaluate potential mechanisms involved in perioperative ischemic events.
    

Detailed description: 
      The study consists of four sub studies

        -  Troponin monitoring implementation - Sub study A

        -  Preoperative and postoperative hs-cTnT threshold - Sub study B

        -  Economic analysis - Sub study C

        -  Advanced cardiac imaging case-control study - Sub study D

      Study A:To implement and evaluate a Troponin T monitoring program in patients with high
      cardiovascular risk undergoing major non-cardiac surgery, the investigators will include
      prospectively patients with one or more of the following inclusion criteria (intervention
      cohort). Age, sex, type of surgery, revised cardiac risk index, history of coronary artery
      disease, history of cardiac arrest, history of congestive heart failure, history of
      peripheral vascular disease, history of stroke, history of a transient ischemic attack,
      chronic renal failure, history of deep venous thrombosis or pulmonary embolism, diabetes,
      hypertension, current atrial fibrillation, chronic obstructive pulmonary disease, type of
      treatment (statins and antithrombotic treatments) will be collected.

      The investigators will obtain three determinations of Roche high-sensitive troponin T (99th
      percentile (14 ng/L) for each patient: preoperative (during the preoperative visit or just
      before surgery), 48h, and 72h after surgery. If a rise and/or fall of hs-cTnT with at least
      one value above the 99th percentile upper reference is detected, a clinical evaluation and a
      12-lead ECG will be performed. If no ECG changes, ischemic symptoms, or pulmonary edema to
      fulfill the diagnostic for PMI the patients will undergo an echocardiographic study.

      Study B: All patients included in study A (see above) will included. The investigators will
      measure high sensitivity cardiac troponin T using a Roche Elecsys 2010 analyzer (limit of
      detection 5.0 ng/L, 99th percentile 14 ng/L, a 10% coefficient of variation at 13 ng/L) at
      three predefined time points: preoperatively (during the preoperative visit or just before
      surgery), at 48h and 72h after surgery. The main outcome will be 30 day and 1 year mortality.

      Study C: To analyze the cost-effectiveness of a hs-cTnT screening program for the detection
      of PMI compared to the current practice (no screening). The investigators will structure a
      model as a decision tree analysis. Two alternatives will be considered: the application of
      screening program for detection of PMI versus current practice, based on the application of
      standard treatments in the presence of ischemic symptoms.

      Study D: All the patients from hs-cTnT screening study mentioned above (A) who fulfill MINS
      criteria will be recruited in this study. After obtaining written informed consent, all
      variables included risk factors, comorbidities, medical treatment and perioperative data will
      be recollected by researchers. Within the postoperative hospitalization period, CTA and MRI
      studies will be performed in all cases.

      Two groups of patients will be distinguished :

        -  MINS/PMI group: composed by patients with hs-cTnT value higher than 50% of preoperative
           level, without symptoms, without ECG changes related to ischemia, neither new wall
           abnormalities in the postoperative echocardiogram. Moreover PMI group will be composed
           by patients with perioperative myocardial infarction according the current definition.

        -  Control group: composed by patients without PMI or MINS.

      After a matching analyses for the principal confounding factors (age, sex, Lee index, type of
      surgery), one control for each case will be selected to complete CTA and MRI examinations.

      In MRIs the investigators will do an analysis of global and segmental contractility baseline
      perfusion, a pharmacological stress with adenosine, and an assessment of necrosis and
      myocardial viability by studying late gadolinium enhancement contrast. In CTAs the
      investigators will evaluate plaque morphology, plaque size and composition, stenosis and
      remodeling index.

      Given these findings, and with the information provided by clinical history and eventual ECG
      changes, the investigators will classify MINS patients as (1) due to plaque rupture, (2)
      supply-demand mismatch, (3) non-ischemic cardiac cause, or (4) non-cardiac cause.
    

Intervention name(s): High sensitive Troponin T monitoring
Intervention type(s): Other
Intervention description(s): Three determinations of Roche high-sensitive troponin T (99th percentile (14 ng/L) for each patient: preoperative (during the preoperative visit or just before surgery), 48h, and 72h after surgery. If a rise and/or fall of hs-cTnT with at least one value above the 99th percentile upper reference is detected, a clinical evaluation and a 12-lead ECG will be performed. If no ECG changes, ischemic symptoms, or pulmonary edema to fulfill the diagnostic for PMI the patients will undergo an echocardiographic study.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Adults ≥ 65 years or < 65 years with documented cardiovascular disease (history of coronary
        artery disease, history of congestive heart disease, history of stroke, history of
        peripheral vascular disease) undergoing a major non-cardiac surgery can considered for
        eligibility. Eligible Patients will be approached for informed consent after surgery and
        before hospital discharge.
      
Keywords: Ultrasensitive Troponin T; MINS; Cost-effectiveness; Myocardial Ischemia