Biomarkers for infarct diagnosis and rapid rule-out/rule-in of acute myocardial infarction
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Introduction Despite recent developments in omicsbased technologies, cardiac troponins (cTn) maintained their role as the preferred biomarkers of myocardial injury and myocardial infarction in the 4th version of the Universal Definition of Myocardial Infarction (UDMI) [1] and in current national guideline recommendations [2, 3]. Although use of the 99th percentile value of a healthy reference population to define an abnormal cTn concentration has some shortcomings [4], lack of a better alternative supports its use for the diagnosis of myocardial infarction (MI). With the development of high-sensitivity (hs)-cTn assays, it became evident that the diagnostic process can be further accelerated [5–7]. Whereas the UDMI definition of MI resides on the 99th percentile value to discriminate abnormal myocardial injury versus physiological myocardial cell turnover [8, 9], fast diagnostic protocols are now optimized to achieve the highest sensitivities and negative predictive values for rule-out, while at the same time the highest specificities and positive predictive values (PPVs) [10, 11]. Using a strategy that requires two sets of diagnostic thresholds, i.e., separately for rule-out and rule-in, creates a grey zone between rule-out and rule-in that does not fit the diagnostic criteria and increases the difficult-to-diagnose cases. The present review provides an overview on the state-of-the-art diagnosis, existing controversies, and profound insights into unmet needs and knowledge gaps, as well as caveats associated with the
Evangelos Giannitsis · Vinayak Gopi Medizinische Klinik III, Heidelberg, Germany
Biomarkers for infarct diagnosis and rapid rule-out/rule-in of acute myocardial infarction diagnosis of MI and the use of faster diagnostic protocols.
4 Definition of the threshold of relevant
rise and/or fall 4 The preference of relative or absolute
Biomarkers of myocardial necrosis in the universal MI definition At present, the 4th version of the UDMI [1] defines an MI in the presence of a cTn value exceeding the 99th percentile value showing a relevant acute concentration change (“rise and/or fall”) in symptomatic patients having a clinical context of myocardial ischemia (. Table 1). Moreover, the 4th UDMI lists and defines subtypes of MI (. Table 2). The UDMI definition is biologically plausible, although there is some debate around a number of components of this definition: 4 Variability of the 99th percentile depending on definition of health, exclusion/inclusion criteria, screening methods, statistical method of determination, identification and handling of outliers, representation of diverse ethnicities 4 Clinical usefulness of sex-specific cut-offs
concentration changes 4 The role of biological variability 4 Type 2 MI and MI with non-
obstructed coronary arteries (MINOCA) 4 Missed MI 4 Periprocedural myocardial injury/ type 4a-5 MI 4 Unstable angina
Missed myocardial infarction In the pre-troponin era, unrecognized MI was frequent, ranging between 22–40% of all MI [12]. Factors for missing MI include older age, female sex,
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