Abstract
Infarct size is a major predictor of subsequent cardiovascular events following ST-segment elevation myocardial infarction (STEMI) and is frequently used in clinical trials focused on cardioprotection. Approximately assessed through serial blood sampling, it can be accurately measured by imaging techniques, e.g. cardiac magnetic resonance imaging, which is the actual gold standard for infarct size determination but with limited availability in daily practice. We developed a mathematical biomarker kinetic model based on pharmacokinetic compartment models to easily and accurately estimate infarct size using individual data from five clinical trials evaluating the impact of conditioning therapies in STEMI between 2005 and 2013. Serial blood sampling was available in all studies with data regarding creatine kinase (CK), CK specific of cardiomyocytes (CK-MB) and cardiac troponin I. Our model allowed an accurate estimation of biomarker release as a surrogate marker of infarct size and a powerful assessment of conditioning treatments. This biomarker kinetic modelling approach identified CK-MB as the most accurate biomarker in determining infarct size and supports the development of limited sampling strategies that estimate total biomarker amount released with a lower number of samples. It will certainly be a useful add-on to future studies in the field of STEMI and cardioprotection.
Highlights
In the context of myocardial ischemia-reperfusion injury, infarct size is a key predictor of subsequent major cardiovascular events[1, 2]
This study is the first to describe a simple and reliable estimation of the amounts (BTOT) of necrosis biomarkers (CK, cTnI, creatine kinase (CK)-MB) that are released by injured myocardium, obtained using a mathematical description of their kinetics
Evaluating the effect of a treatment on Major adverse cardiac and cerebrovascular events (MACCE) reduction after myocardial infarction in patients receiving up-to-date treatments can only be performed in large clinical trials enrolling a large number of patients
Summary
In the context of myocardial ischemia-reperfusion injury, infarct size is a key predictor of subsequent major cardiovascular events[1, 2]. Cardiac MRI is usually not available during off-business hours and non-working days This renders the assessment of infarct size in the early phase of acute myocardial infarction still mainly dependent on serial blood measurements of biomarkers that are more likely to be available on a 24/7 basis. The relevance of these conditioning techniques are assessed by measuring the total amount of necrosis marker released by the injured myocardium using the peak and/or the area under the concentration versus time curve (AUC) of CK, CK-MB and cTnI. These surrogate endpoints are used because of their availability and their known correlation with infarct size[11,12,13]. The quantification of all of these phenomena should allow an accurate quantification of the amount of biomarker released by injured tissue, a variable that could be of precious value in cardioprotection studies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
