Perioperative Myocardial Ischemia: Troponin Monitoring,Cost-effectiveness, Insights Into Pathophysiology

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.

Inclusion criteria

• Age ≥ 65 years.
• Age < 65 years and documented cardiovascular disease (history of coronary artery disease, history of congestive heart disease, history of stroke, history of peripheral vascular disease).
• Renal insufficiency (GF <60ml/min).

Exclusion criteria

Patients undergoing non cardiac surgery that do not require an overnight hospital admission or that only receive infiltrative (i.e., local) or topical anesthesia.