Taking a closer look into the diagnosis of acute coronary syndrome

Diagnosis and management of acute myocardial infarction (MI), particularly biomarker testing in suspected acute coronary syndromes (ACS), belong to the fastest moving targets in cardiovascular medicine. Therefore, a special issue has now been dedicated to provide a state-of-the art overview on the diagnosis of ACS and to provide more detailed information on new protocols and novel biomarkers that facilitate earlier and more accurate diagnosis of ACS. In this context, Vafaie [1] has drafted an update on the diagnosis and management of non-ST segment elevation (NSTE)-ACS highlighting the most important recommendations of the 2015 ESC guidelines [2]. These guidelines advocate the use of a 3-h diagnostic algorithm which is now regarded the standard protocol to rule-out and rule-in NSTEMI, provided hsTn assays are available. Even faster diagnostic protocols with re-testing of hsTn after only 1 or 2 h are also recommended by ESC guidelines as alternatives, with or without the use of clinical scores [2, 3]. Distinct to other available choices, the 1-h algorithm requires the availability of validated hsTnT or hsTnI assays [2, 3]. However, accelerated diagnostic protocols and even instant rule-out of NSTEMI may be accomplished even in the presence of conventional or contemporary sensitive troponin assays, particularly when used together with copeptin, a normal ECG and a clinical score indicating a low or intermediate risk. Copeptin is a surrogate marker of vasopressin and values are elevated in patients with severe endogenous stress and in patients with cardiovascular failure [4]. Copeptin measured together with cTn has been successfully introduced into the 2015 ESC guidelines [2] as an effective algorithm not only to rule-out NSTEMI on admission but also to detect low risk patients with unstable angina that might be discharged home earlier without an excess risk of death, MI or other major cardiovascular events [5]. An overview on the diagnostic role of copeptin in ACS is provided by Möckel et al. in another review [6] in this special issue. The authors nicely summarize the current strategies for the initial diagnostic approach in patients with suspected MI with a special focus on the added benefits of copeptin measurement for instant rule-out and earlier discharge. An interesting expansion of early diagnosis is provided by Stengaard et al. in this issue [7] who reflects on the role of copeptin and cTn testing in the pre-hospital phase pointing to the potential role of pre-hospital triage using biomarkers for more accurate earlier diagnosis and thus improved routing of high risk patients with suspected ACS to dedicated interventional centers avoiding re-routing or secondary transports in ambulances.

High sensitivity troponins have become the preferred biomarkers for diagnosis of MI due to their absolute tissue specificity. However, the improved analytical sensitivity has facilitated the detection of truly troponin positive patients caused by myocardial injury due to miscellaneous cardiac causes other than coronary ischemia. Thus, the clinical sensitivity has increased at the cost of clinical specificity despite the exclusive tissue specificity. von Jeinsen and Keller [8] elaborates this issue in his review article with emphasis on the loss of clinical specificity. He discusses ways to overcome this issue by utilization of comorbidity, sex- and age-optimized decision cutoffs. Moreover, he provides information on non-type I MI related troponin elevations and how to avoid misdiagnosis and under-treatment of MI. The highly debated topic whether to implement sex- and age-specific cutoffs is separately addressed by Mueller-Hennessen and Giannitsis [9]. In their review, the inconsistency of study findings and recommendations is highlighted with a personal view on the usefulness and anticipated acceptability of sex- and age-specific cutoffs. Although the diagnostic performance of hsTn is improved by optimized cutoffs for age and sex, the diagnostic re-classification is small and the impact on survival is negligible. More importantly, implementation of complex diagnostic algorithms is questionable.

An increasingly important point in the diagnostic process is the role of cardiac imaging in the initial work-up and differential diagnosis of suspected ACS. Andre et al. [10] discuss state-of-the-art and novel approaches using cardiovascular magnetic resonance and cardiac computed tomography in suspected ACS and for the differential diagnoses of acute and chronic myocardial injury. The authors give an overview on the strengths and weaknesses of both methods. They also describe the different principles and diagnostic targets of CMR and CCT in ACS and which protocols can be used for accurate and fast diagnosis. Finally, Samani and Meder [11] provide a nice overview on the potential role of microRNA for diagnosis of ACS and give information on available technologies and their advantages and limitations. MicroRNAs (miRNAs) as part of the human regulatory transcriptome are expressed intracellularly and released into various body fluids including blood. MiRNA dysregulation is associated with a wide range of cardiac diseases including ACS. However, biochemical evaluation of ACS requires fast and accurate assay technologies. Until now, quantification of this small non-coding RNAs is performed in the research laboratory. Advanced technologies that might fulfill the requirements of emergency medicine are presented and discussed.

All authors have to be congratulated for their contributions that give a representative state-of-the-art across different important aspects in the diagnosis and differential diagnosis of MI. Space limitations precluded us from discussing other interesting and evolving issues concerning ACS, including the role of echocardiography and updates on pharmaceutical and interventional treatments in ACS.