Myocardial Injury Following Non-cardiac Surgery
Condition: Myocardial Injury; Surgery--Complications
MeSH terms: Wounds and Injuries
Study type: Observational

Summary: 
      It is estimated that > 200 million patients in the world undergo surgery each year of which
      approximately 10 million will suffer from a myocardial injury in the perioperative period.
      Mortality is high in patients with myocardial injury since it often goes undiagnosed and
      management is unclear. In contrast to myocardial infarction diagnosed in the emergency room
      (non-surgical patient) where treatment is well established today, patients suffering from a
      perioperative myocardial injury have a poorer outcome. Additionally, the patho-physiology of
      myocardial injury is unknown in the individual patient, non-invasive diagnostic tools are not
      widely available and treatment remains unknown.

      Most cases of myocardial injury in Non-cardiac surgery (MINS) are seen within the first 48-72
      h after surgery and a majority have no symptoms. Many patients developing MINS are < 65 years
      old and non-diabetics, an age group that usually does not have coronary artery disease. A
      elevated Troponin T (TnT) without symptoms or ECG changes, typically occurring in the
      perioperative period, is an independent predictor of 30-day mortality. Surgical trauma also
      causes an increase in several pro-inflammatory cytokines, which together with sympathetic
      over-activity and platelet activation, leads to a hyper-coagulant state, and in turn may
      cause coronary thrombosis. It is possible that some cases of MINS also result from oxygen
      supply-delivery mismatch. To our knowledge, no study has investigated the cause of MINS in
      patients presenting with increased TnT in the perioperative period. Our aim is therefore to
      investigate patients having MINS in order to better understand its aetiology and subsequently
      develop focused strategies to reduce risks.
    

Detailed description: 
      Introduction:

      It is estimated that > 200 million patients in the world undergo surgery each year of which
      approximately 10 million would suffer from a myocardial injury in the perioperative period.
      Mortality is high in this group of patients since it often goes undiagnosed, the
      patho-physiology of myocardial injury is unclear, non-invasive diagnostic tools are not
      widely available and treatment is unknown.

      Multiple studies have shown that > 10% of patients > 65 years and undergoing non-cardiac
      surgery have an increase in Troponin T (TnT). In the POISE study including 8331 patients, the
      authors found that 5.7% of the placebo group suffered from a myocardial injury within the
      30-day postoperative period. In the recently published data from the VISION study including >
      15,000 patients, the authors demonstrated that patients with peak perioperative TnT values of
      < 0.01, 0.02, 0.03-0.29 and > 0.30 ng/L had a 30-day mortality of 1%, 4%, 9.3% and 16.9%
      respectively. Furthermore, an elevated TnT without symptoms or ECG changes are an independent
      predictor of 30-day mortality. It is possible that some cases of myocardial injury in
      Non-cardiac surgery (MINS) result from oxygen supply-delivery mismatch due to severe
      perioperative hypotension, and possibly persistent tachycardia but coronary artery thrombosis
      cannot be excluded in these patients. It is well known that surgical trauma causes an
      increase in several pro-inflammatory cytokines which, together with sympathetic
      over-activity, leads to a hypercoagulable state due to platelet activation, and a
      predisposition to thrombosis. In one study, it was found that approximately 1/3 of the
      patients had evidence of intracoronary thrombosis at autopsy.

      Myocardial infarction with non-obstructive coronary artery (MINCA) has recently received
      greater attention in the literature. The underlying patho-physiology responsible for MINCA
      revealed the presence of a typical myocardial infarct on cardiac magnetic resonance imaging
      in only 24% of patients, with myocarditis occurring in 33% and no significant abnormality in
      26%. A rare cause of MINCA is Takotsubo cardiomyopathy, also called stress cardiomyopathy.
      Recently, coronary angiography using computerized tomographic angiography (CTA) has added a
      new dimension to the diagnostic armamentarium available to the clinician. Using advanced
      imaging techniques and low radiation, it is today possible to determine quite accurately
      coronary artery anatomy and thereby determine stenotic lesions in the coronary vasculature.
      Echocardiography can be easily performed by an experienced technician, the images stored
      digitally and evaluated subsequently by specialists. The availability of continuous
      perioperative monitoring of several hemodynamic indices as well as regular blood gas
      analysis, may enable determination of oxygen demand-supply mismatch.

      Methods:

      This is a case-control study in patients undergoing major, non-cardiac surgery. Permission
      will be obtained from the Ethics committee prior to patient recruitment and Good Clinical
      Practice guidelines will be followed in all patients. Two parts to the study are planned:

      Part 1. Screening of all patients undergoing vascular surgery (arterial surgery) where
      demographic data, co-morbidities, laboratory and perioperative haemodynamic parameters,
      postoperative complications will be recorded and patients followed up at 30, 90 and 365 days
      after surgery via medical records. This group is estimated to include 500 patients. Informed
      consent will be obtained from these patients for data collection and follow-up via medical
      records.

      Part 2. Patients with a significant increase in TnT (estimated 10% = 50 patients) will
      undergo cMRI (see below) and a matched control without increase in TnT will also undergo
      similar protocol as described below.

      Verbal and written informed consent will be obtained from all patients willing to participate
      in the second part of the study. The following laboratory tests would be performed
      preoperatively (baseline values): routine bloods, creatinine, urea, estimated glomerular
      filtration rate (eGFR), C-reacting proteins (CRP), white blood cell (WBC) count, TnT,
      N-Terminal pro-Brain Natriuretic Peptide (NT-pro BNP), lipid profile, 12-lead EKG and
      echocardiography (ECHO).

      Anaesthesia and Surgery The surgical and anaesthetic techniques would be determined by
      physicians responsible for the patient and according to established hospital routines and
      practices. Patient records would be used for the determination of adverse events according to
      a standardized protocol. Patient characteristics, pre-operative risk factors, laboratory data
      and follow-up data would be obtained from medical records. Prophylaxis against deep vein
      thrombosis, surgical infections and fluid and electrolyte balance would also follow hospital
      practice. All included patients would be admitted to the post-anaesthesia care unit (PACU)
      overnight, and longer if deemed necessary by the attending Anaesthesiologist. Patients would
      be continuously haemodynamically monitored and anaesthesia records would be maintained for
      independent assessment by a blinded reviewer. Drop in blood pressure that persists despite
      short-acting vasopressors will be treated by infusion of noradrenaline perioperatively.
      Hs-TnT would be repeated in all patients at 24, 48 and 72 h postoperatively. Plasma NT-pro
      BNP would be re-assessed at 24 h. A 12-lead EKG would be recorded in all patients with
      elevated high-sensitivity TnT (hs-TnT) at the time of first occurrence and 48 h later.
      Platelet function tests, microparticles as well as coagulation tests would be performed
      periodically in the perioperative period. Further laboratory tests would be performed as
      needed at the discretion of the attending physician.

      Cardiac Magnetic Resonance Imaging (cMRI) would be performed within 1-3 days of detecting a
      rise in TnT in the study population as well as the control group. This will include a
      drug-induced (Adenosine) stress test of the heart in connection with the examination. cMRI
      will allow an increased opportunity to identify an acute myocardial injury, even of a minor
      nature, and minimises the risk of radiation to patients (as with CTA). The cMRI scan will be
      performed within 24-48 hours after elevated levels of cTnT (cardiac troponins) are measured.

      Echocardiography: Protocolized ECHO would be performed 24 h after detection of raised TnT in
      the study group, and at corresponding time period in a matched group of controls. The ECHO
      will be recorded and subsequently interpreted by an experienced clinical
      physiologist/cardiologist to determine wall motion abnormalities and systolic and diastolic
      function.

      When deemed necessary by the attending Cardiologist, the following may also be performed:

      Conventional invasive coronary angiography: This will only be done at the discretion of the
      attending Cardiologist and in agreement with the patient and surgeon at an appropriate time
      point after surgery, if deemed necessary.

      The control group will be matched for age, sex and co-morbidities described in the revised
      cardiac risk score (myocardial ischemia, cardiac failure, stroke, diabetes mellitus, renal
      insufficiency and major-risk surgery) (ref) and grouped into < 3 risk factors and >/= 3 risk
      factors.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with an increase in Troponin T (> 20 ng/L) or a > 50% rise from preoperative
        values after induction of anesthesia will form the Myocardial injury Group while those
        without an increase in Troponin T (< 14 ng/L) will form the Control group
      
Biospecimen description: 
      Plasma
    
Keywords: troponin; major surgery