Evangelos Giannitsis

Recommendations for the use of cardiac troponin measurement in acute cardiac care

The release of cardiomyocyte components, i.e. biomarkers, into the bloodstream in higher than usual quantities indicates an ongoing pathological process. Thus, detection of elevated concentrations of cardiac biomarkers in blood is a sign of cardiac injury which could be due to supply-demand imbalance, toxic effects, or haemodynamic stress. It is up to the clinician to determine the most probable aetiology, the proper therapeutic measures, and the subsequent risk implied by the process. For this reason, the measurement of biomarkers always must be applied in relation to the clinical context and never in isolation. There are a large number of cardiac biomarkers, but they can be subdivided into four broad categories, those related to necrosis, inflammation, haemodynamic stress, and/or thrombosis. Their usefulness is dependent on the accuracy and reproducibility of the measurements, the discriminatory limits separating pathology from physiology, and their sensitivity and specificity for specific organ damage and/or disease processes. In recent years, cardiac biomarkers have become important adjuncts to the delivery of acute cardiac care. Therefore, the Working Group on Acute Cardiac Care of the European Society of Cardiology established a committee to deal with ongoing and newly developing issues related to cardiac biomarkers. The intention of the group is to outline the principles for the application of various biomarkers by clinicians in the setting of acute cardiac care in a series of expert consensus documents. The first of these will focus on cardiac troponin, a pivotal marker of cardiac injury/necrosis.

Recommendations for the use of natriuretic peptides in acute cardiac care : A position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care

Recommendations for the use of natriuretic peptides in acute cardiac care : A position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care

Biomarkers of Necrosis for Risk Assessment and Management of ST-Elevation Myocardial Infarction

The diagnosis and immediate initiation of reperfusion therapy in patients with acute ST-elevation myocardial infarction (STEMI) are based on results of the standard 12-lead electrocardiogram. Because the appearance of cardiac markers of myocardial injury in the blood is delayed relative to the onset of symptom, cardiac markers are neither helpful for early diagnosis nor should their results be awaited before initiation of reperfusion therapy. Nevertheless, there are four important reasons to measure cardiac markers of necrosis in patients with STEMI: (1) confirmation of diagnosis, (2) monitoring of efficiency of reperfusion, (3) assessment of risk, and (4) infarct sizing.

Diagnosing cardiovascular diseases

The cardiac specific troponins (cTn) are the preferred biomarkers for the diagnosis of myocardial infarction. They are measured quantitatively in the serum. The use of highly sensitive cTn assays made the measurement of other markers (such as myoglobin, CK-MB mass, fatty acid binding protein) redundant, because they confer no added diagnostic benefit. To date, highly sensitive cTn assays are available only on two POCT benchtop devices. Laboratory assays used in heart failure include the use of BNP and NT-pro-BNP markers as recommended by the European and American Associations for the screening and diagnosis of heart failure. POCT methods are now becoming capable of measuring these cardiac markers with high sensitivity.

Diagnostik kardiovaskulärer Krankheiten

Der bevorzugte Biomarker in der Herzinfarktdiagnostik ist das quantitativ im Serum gemessene kardiale Troponin (cTn) wegen seiner Gewebespezifitat. Bei Verwendung hochsensitiver cTn-Assays wird die Bestimmung weiterer Marker wie Myoglobin, CK-MB Masse, FABP nicht empfohlen, da diese Biomarker keinen diagnostischen Zusatznutzen bringen. Hochsensitive cTn-Assays werden bislang von zwei POCT-Benchtop-Geraten angeboten. Fur die labormedizinische Begleitung der chronischen Herzinsuffizienz stehen heute mit dem BNP und dem NT-pro-BNP Marker zur Verfugung, deren Einsatz von Europaischen und Amerikanischen Fachgesellschaften fur Screening und Diagnostik der Herzinsuffizienz empfohlen wird. POCT-Methoden zur Messung sind bereits entwickelt worden.

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, sexand 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 sexand 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 sexand 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 *Corresponding author: Prof. Dr. Evangelos Giannitsis, Medizinische Klinik III, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany, Phone: +49-6221-56-38686, Fax: +49-6221-56-5516, E-mail: evangelos_giannitsis@med.uni-heidelberg.de Hugo A. Katus: Department of Internal Medicine III, Cardiology, University Hospital Heidelberg, Germany

Clinical Decisions in Acute Patients: ACS-POCT-Hypertension and Biomarkers

1 Division of Emergency Medicine/CPU, Charite-University Medicine Berlin, Campus Virchow-Klinikum and Campus Charite Mitte, 13353 Berlin, Germany 2 Kerckhoff Heart and Thorax Center, Bad Nauheim and Medical Clinic I, University of Giessen, 61231 Bad Nauheim, Germany 3Department of Internal Medicine III, Cardiology, University Hospital Heidelberg, 69120 Heidelberg, Germany 4 European Society for Emergency Medicine, EuSEM and Emergency Medicine Department, Faculty of Medicine, Rennes University Hospital, 35033 Rennes, France

Quantitative Analyse und Visualisierung der Herzfunktionen

Die computergestutzte bildbasierte Analyse der Herzfunktionen ist mittlerweile Standard in der Kardiologie. Die verfugbaren Produkte erfordern meist ein hohes Mas an Benutzerinteraktion und somit einen erhohten Zeitaufwand. In dieser Arbeit wird ein Ansatz vorgestellt, der dem Kardiologen eine grostenteils automatische Analyse der Herzfunktionen mittels MRT-Bilddaten ermoglicht und damit Zeitersparnis schafft. Hierbei werden alle relevanten herzphysiologsichen Parameter berechnet und mithilfe von Diagrammen und Graphen visualisiert. Diese Berechnungen werden evaluiert, indem die ermittelten Werte mit manuell vermessenen verglichen werden. Der hierbei berechnete mittlere Fehler liegt mit 2,85 mm fur die Wanddicke und 1,61 mm fur die Wanddickenzunahme immer noch im Bereich einer Pixelgrosse der verwendeten Bilder.

Cardiac Biomarkers in the Diagnostic Workup of Pulmonary Embolism

Confirmation of pulmonary embolism (PE) must be followed by risk stratification in order to obtain information on short-term prognosis and determine the need for more aggressive therapy such as thrombolysis or surgical/interventional embolectomy. The cardiospecific troponins, I and T, and the brain-type natriuretic peptide (BNP) or its biologically inactive N-terminal fragment, NT-pro BNP, are frequently elevated in PE. Although the exact mechanisms are still unknown, there is a link between the presence of cardiac troponins, BNP, or NT-pro BNP in blood and the presence and severity of right ventricular dysfunction resulting from PE. Thus, absence of cardiac troponin or natriuretic peptide elevation is associated with a benign clinical course that justifies conservative treatment, i.e., heparin anticoagulation followed by oral vitamin K antagonists. On the other hand, the presence of elevated cardiac troponins, BNP, or NT-pro BNP does not necessarily predict an adverse outcome when biomarker tests are used alone for risk stratification of PE. The following chapter presents an overview of the pathophysiology and prevalence of elevated biomarkers in PE and summarizes the evidence supporting a novel risk stratification algorithm based on biomarker testing and echocardiography or other imaging modalities.