Determination of Biochemical Onset Time for ST-Segment Elevation Myocardial Infarction and Comparison With Patient-Reported Symptom Onset Time

ST segment elevation myocardial infarction (STEMI) is one of the leading causes of death across the world (1) and immediate treatment with either thrombolytics or percutaneous coronary intervention (PCI) results in lower mortality (2,3,4). Prior studies have demonstrated that in patients with STEMI approximately 50% of jeopardized myocardium undergoes necrosis in the first hour, and after 6 hours, myocardial salvage is minimal or absent (5,6). Among such patients each minute of delay in reperfusion treatment raises 1-year mortality; in fact, the risk of 1-year mortality increases by 7.5% for each 30-minute delay (7).

As the outcome of reperfusion treatment in STEMI is time dependent, it is essential to accurately determine the time of onset of myocardial infarction. It is standard clinical practice to take the time of symptom onset as a surrogate for artery occlusion time, and this helps in decision making about mode of reperfusion in STEMI-patients. However symptom onset is a subjective parameter and affected by multiple factors such as recall issues in elderly patients and preceding unstable angina symptoms before artery occlusion. This mandates need for an objective method to know the artery occlusion time. Different time intervals are defined for STEMI patients that include, "artery occlusion to symptom onset time", "symptom onset to first medical contact time" and "door to balloon time" and combination of all these intervals is "Total Ischemic time" i.e. the time between artery occlusion and re-opening, which is strongly correlated with 1-year mortality (8).

In a recent study by Mahmoud et al. (9) an objective method, biochemical onset time is proposed for estimation of artery occlusion time using serial cardiac troponin T (cTnT) levels in patients with STEMI. However, this study was retrospective, had an average of two measurements of cTnT for each patient, peak troponin level was frequently missing and newer earlier detectable biomarkers such as high sensitive Troponin I (hsTnI) were not used.

The objective of this pilot study is to observe if there is any role of multiple samples of markers of myocardial injury in prediction of the biochemical onset time. We plan to use multiple samples (four) of hsTnI for each patient using the same method as above (9); and we will compare the biochemical ischemic time with the patient reported symptom onset time. Secondarily, we will try to determine whether a single sample of multiple cardiac biomarkers with different release kinetics drawn at time of patient presentation in emergency room (ER) can also predict precise time of onset of myocardial infarction, which would be a revolutionary finding in STEMI patients' early management. For this purpose we will use three markers including cardiac specific myoglobin (CS-Mb) and Creatinine kinase-Mb (CK-Mb) (10). We also plan to test three other novel markers which has previously shown to have some role in post MI prognosis and cardiac event risk prediction in general population {(Mean neutrophil volume (MNV), Gamma Prime fibrinogen (γ' Fibrinogen) and heart type fatty acid binding protein (h-FABP)} to assess whether it has a possible predictive value to assess time of onset of MI. Lastly, we plan to assess the prognostic value of biochemical ischemic time versus conventional ischemic time for the outcomes of major adverse cardiovascular events (MACE) at hospital discharge and 30 days post MI, infarct size using CMR and echo based parameters.

OBJECTIVES