Myocardial injury and myocardial infarction: the various ways of losing myocytes and their prognostic impact

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. What an infarction is has been defined differently over the past decades. In the 1950s physicians had only clinical signs and the ECG,1 then biomarkers were introduced such as lactate dehydrogenase (which was not specific), then myoglobin (which gave faster answers, but was also not specific), then creatinine kinase (CK) and its cardiac isoform CK-MB became available and remained the gold standard for many years. With the introduction of troponins,2–4 even small infarcts could be detected with a high sensitivity and specificity. This Focus Issue on myocardial infarction contains the ‘Fourth universal definition of myocardial infarction (2018)’ authored by Kristian Thygesen and colleagues from the ESC Scientific Document Group.5 What is new in the fourth definition? Importantly, the group now introduces a differentiation between myocardial injury and myocardial infarction. As such, many conditions with increased troponins represent myocardial injury rather than myocardial infarction, in particular troponin also rises after cardiac and non-cardiac procedures. Furthermore, the role of imaging to differentiate different forms of infarction is discussed. This document is complemented by ‘The year in cardiology 2018: acute coronary syndromes’ wherein Petr Widimsky from the Charles University in Prague, Czech Republic and colleagues summarize the most important novelties in acute coronary syndromes (ACS) in 2018.6 Novel mechanisms of ACS include alterations of immunity, the increasing importance of plaque erosion, the role of troponin in the very early diagnosis, and cardiac myosin-binding protein as a novel biomarker with great potential for risk stratification. Furthermore, the role of gender in ACS, in particular spontaneous coronary dissection which affects mainly women, and novel forms of dual antiplatelet therapy and oral anticoagulation attracted a lot of interest. Routine oxygen therapy is definitively ruled out in the acute phase, while periprocedural antithrombotic medication remains an issue, as does multivessel percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients without shock. Unresolved questions and unmet needs remain and should be addressed in 2019. Patients with ACS who present initially as STEMI on the ECG but, subsequently, show complete normalization of the ST-segment and relief of symptoms before reperfusion therapy are referred to as having transient STEMI and pose a therapeutic challenge.7 In their FAST TRACK entitled ‘Timing of revascularization in patients with transient ST-segment elevation myocardial infarction: a randomized clinical trial’, Niels van Royen and colleagues from the Radboud University Medical Center in Nijmegen, The Netherlands noted that it is unclear what the optimal timing of revascularization for these patients is and whether they should be treated with a STEMI-like or a non-STEMI-like invasive approach (Figure 1).8 Thus, they randomized 142 transient STEMI patients to an immediate or delayed invasive strategy and measured infarct size by cardiac magnetic resonance imaging (CMR). Infarct size at day 4 was generally small and not different between the immediate and the delayed invasive group, as was left ventricular ejection fraction. Furthermore, there was no difference in major adverse cardiovascular events (MACE) at 30 days. Thus, infarct size in transient STEMI is small and is not influenced by an immediate compared with a delayed strategy, nor were short-termMACE different between the treatment groups. These clinically relevant findings are accompanied by an interesting Editorial by David P. Faxon from the University of Chicago in Illinois, USA.9 (A and B) Typical electrocardiograms of transient ST-segment elevation myocardial infarction. (C) cardiac magnetic resonance imaging of typical transient ST-segment elevation myocardial infarction patient. (D) Similar study outcomes between the treatment groups. AUC, area under the curve; CK-MB, creatine kinase-MB; LV, left ventricle; LVEF, left ventricular ejection fraction; MVO, microvascular obstruction; NA, not applicable (from Lemkes JS, Janssens GN, van der Hoeven NW, van de Ven PM, Marques KMJ, Nap A, van Leeuwen MAH, Appelman YEA, Knaapen P, Verouden NJW, Allaart CP, Brinckman SL, Saraber CE, Plomp KJ, Timmer JR, Kedhi E, Hermanides RS, Meuwissen M, Schaap J, van der Weerdt AP, van Rossum AC, Nijveldt R, van Royen N. Timing of revascularization in patients with transient ST-segment elevation myocardial infarction: a randomized clinical trial. See pages 283–291). Thrombus formation is essential for haemostasis after injury; however, in all other conditions intravascular thrombus formation should be prevented.10,11 The endogenous fibrinolytic system serves to prevent lasting thrombotic occlusion and may be the underlying mechanism of transient STEMI following initiation of coronary thrombosis discussed above, and may also be relevant for outcomes.12 In their article ‘Impaired endogenous fibrinolysis in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention is a predictor of recurrent cardiovascular events: the RISK PPCI study’ Diana Adrienne Gorog and colleagues from the Imperial College London in the UK evaluated the role of impaired endogenous fibrinolysis in 496 STEMI patients undergoing primary PCI.13 Blood was tested upon arrival, at discharge, and at 30 days using the point-of-care Global Thrombosis Test. Endogenous fibrinolysis was significantly impaired in 14%, and was highly predictive of recurrent MACE, driven by cardiovascular death and MI (Figure 2). Fibrinolysis remained strongly predictive of MACE after adjustment for conventional risk factors. Net reclassification showed that adding impaired fibrinolysis improved the prediction of recurrent MACE by >50%. Patients with spontaneous ST-segment resolution prior to primary PCI had more rapid, effective fibrinolysis than those without. Thus, in line with previous results from the PLATO trial,14 endogenous fibrinolysis assessment can identify patients with STEMI who remain at very high cardiovascular risk despite guideline-based management. These intriguing findings are put into context in an Editorial by Frans Van de Werf from KU Leuven in Belgium.15 Impaired endogenous fibrinolysis in patients with ST-segment elevation myocardial infarction presenting for primary percutaneous coronary intervention (PPCI), detected using an automated point-of-care technique in the catheterization laboratory, identifies those at high risk of recurrent major adverse cardiovascular events despite dual antiplatelet therapy and PPCI (from Farag M, Spinthakis N, Gue YX, Srinivasan M, Sullivan K, Wellsted D, Gorog DA. Impaired endogenous fibrinolysis in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention is a predictor of recurrent cardiovascular events: the RISK PPCI study. See pages 295–305). Patients who present with infarction and sudden cardiac arrest still have a dismal outcome.16,17 Continued education of the public at large has been recommended.18 In particular, bystander cardiopulmonary resuscitation (CPR) has been proposed to increase survival rates in out-of-hospital cardiac arrest.19 In their article entitled ‘Bystander cardiopulmonary resuscitation and long-term outcomes in out-of-hospital cardiac arrest according to location of arrest’ Kathrine Sondergaard and colleagues from the Gentofte Hospital in Hellerup, Denmark examined the importance of public or residential location of arrest on temporal changes in bystander CPR and outcomes.20 Arrests witnessed by paramedics were excluded. Of 25 505 out-of-hospital cardiac arrests, 26.4% and 73.6% were in public and residential locations, respectively. Bystander CPR increased during 2001–2014 in both locations from 36.4% to 83.1% in public and from 16.0% to 61.0% in residential locations. Concurrently, 30-day survival increased in public from 6.4% to 25.2% and in residential areas from 2.9% to 10%. Among 2281 surviving to 30 days, 1-year risk of anoxic brain damage or nursing home admission decreased from 18.8% to 6.8% in public, but increased in residential locations from 11.8% to 17.6%. Thus, bystander CPR and 30-day survival more than doubled in both public and residential out-of-hospital cardiac arrest locations over the years. The fact that anoxic brain damage and nursing home admission decreased in out-of-hospital arrests in public, but increased among survivors from residential out-of-hospital arrests is a remaining issue that is further discussed in an thought-provoking Editorial by Daniele Giacoppo from the German Heart Center in Munich, Germany.21 The editors hope that this issue of the European Heart Journal will be of interest to its readers. With thanks to Amelia Meier-Batschelet for help with compilation of this article.