A counterpoint paper: Comments on the electrocardiographic part of the 2018 Fourth Universal Definition of Myocardial Infarction

This is the accepted manuscript of the article, which has been published in Journal of Electrocardiology, 2020, 60, 142-147. https://doi.org/10.1016/j.jelectrocard.2020.04.012 © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license A counterpoint paper: Comments on the Electrocardiographic Part of the 2018 Fourth Universal Definition of Myocardial Infarction Endorsed by the International Society of Electrocardiology (ISE) and the International Society for Holter and Noninvasive Electrocardiology (ISHNE). Yochai Birnbaum1 Miguel Fiol2 Kjell Nikus3 Javier Garcia Niebla4 Ljuba Bacharova5 Sergio Dubner6 Wojciech Zareba7 Peter W. Macfarlane8 Antonio Luiz Ribeiro9 Iwona Cygankiewicz10 Antoni Bayes de Luna11 1. The Section of Cardiology, Baylor College of Medicine. Houston, Texas, USA. 2. Health Research Institute of the Balearic Islands.Hospital Son Espases. Palma. Spain. 3. Faculty of Medicine and Health Technology, University of Tampere, and Finnish Cardiovascular Research Center, Tampere, Finland. Heart Hospital, Tampere University Hospital, Tampere, Finland. 4. Servicios Sanitarios del Area de Salud de El Heirro. Valle del Golfo Health Center, C/ Marcos Luis Barrera, 1.38911-Frontera, El Hierro, Spain. 5. International Laser Center, Bratislava, Slovak Republic and Institute of Pathophysiology, Medical School, Comenius University, Bratislava, Slovak Republic. 6. Clinica y Maternidad Suizo Argentina and De Los Arcos Sanatorio. Buenos Aires, Argentina. 7. Division of Cardiology, University of Rochester Medical Center, Rochester, NY, USA. 8. Institute of Health and Wellbeing, University of Glasgow and Electrocardiology Section, Royal Infirmary, Glasgow, Scotland, UK. 9. Internal Medicine Department, School of Medicine, and Telehealth Center, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. 10. Department of Electrocardiology. Medical University of Lodz, Poland. 11. Cardiovascular Research Foundation. Cardiovascular ICCCProgram, Research Institute Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain. Corresponding author: Yochai Birnbaum, MD. John S. Dunn Chair in Cardiology Research and Education. The Department of Medicine, Section of Cardiology, Baylor College of Medicine. One Baylor Plaza. MS BCM620. Houston, TX 77030. Phone: +1-713-798-2735. Fax: +1-713-798-0270. Email: [email protected]u Abstract: The Fourth Universal Definition of Myocardial Infarction (FUDMI) [published simultaneously in 2018 in numerous journals including Circulation, Journal of the American College of Cardiology and European Heart Journal] focuses mainly on the distinction between non-ischemic myocardial injury and myocardial infarction (MI), along with the role of cardiovascular magnetic resonance, in order to define the etiology of myocardial injury. As a consequence, there is less emphasis on updating the parts of the definition concerning the electrocardiographic (ECG) changes related to MI. Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI and the ECG is the main available tool for i) detecting acute ischemia, ii) triage and iii) risk stratification upon presentation. This review focuses on multiple aspects of ECG interpretation that we firmly believe should be considered for incorporation in any future update to the Universal Definition of MI. Our counterpoint view is that: a) the use of the ECG following coronary artery bypass surgery should be better explored and defined; b) the emphasis in the FUDMI on convex versus concave ST-elevation, which is questionable, should be balanced by the fact that many patients with true ST-elevation MI (STEMI) present with a concave form of ST elevation; c) reciprocal ST-depression in STEMI caused by right coronary artery or left circumflex artery occlusion, should be set against the fact that not all anterior STEMIs present with reciprocal ST-depression which can also be seen in cardiomyopathy and left ventricular hypertrophy; d) the “posterior” leads V7-V9 should be placed on a horizontal line from V4, rather than follow the 5th intercostal space; e) ST-depression in V1-V3 is not a manifestation of ischemia of the basal inferior segment, placed horizontally; f) Interpreting ST-T changes in patients with conduction abnormalities and pacemakers should be further defined. The Fourth Universal Definition of Myocardial Infarction (FUDMI), published simultaneously in 2018 in numerous journals including Circulation, Journal of the American College of Cardiology and European Heart Journal, focuses mainly on the distinction between non-ischemic myocardial injury and myocardial infarction (MI) and the role of cardiovascular magnetic resonance in defining the etiology of myocardial injury, with less emphasis on updating the parts related to the electrocardiographic (ECG) changes related to MI (1). Evidence of myocardial ischemia is a prerequisite for the diagnosis of MI and the ECG is the main diagnostic tool for detecting acute myocardial ischemia, as stated in the document, viz: “Myocardial ischemia in a clinical setting can most often be identified from the patient’s history and from the ECG” (1). Therefore, the definitions of “ischemic changes” should be accurate. The International Society of Electrocardiology (ISE) and the International Society for Holter and Noninvasive Electrocardiology (ISHNE) focus on the ECG and have members that are expert in interpreting ECG changes detected during ischemia and infarction. This counterpoint review focuses on several topics related to the ECG that we believe should be considered to be modified and incorporated into future versions of the document. METHODS: YB, MF, KN, JGN and AB read the FUDMI and communicated about topics related to the ECG that should be discussed in this paper. Those ideas were incorporated into an initial draft by YB that has been circulated to all co-authors for review and approval. Communications were by email, Skype and in person during The International Society of Electrocardiology (ISE) and the International Society for Holter and Noninvasive Electrocardiology (ISHNE) conference in Belgrade 2019. The manuscript has been updated accordingly, until all co-authors approved the final version. The headings in this paper refer mainly to the original sections of the FUDMI (1). MYOCARDIAL INFARCTION ASSOCIATED WITH CORONARY ARTERY BYPASS GRAFTING (TYPE 5 MYOCARDIAL INFARCTION) Although the FUDMI states: “It is important that the postprocedural elevation of cTn values is accompanied by ECG, angiographic, or imaging evidence of new myocardial ischemia/new loss of myocardial viability”, the thresholds for the ECG changes, especially ST deviation, are not mentioned. The document specifies that ST-T changes are common after coronary artery bypass grafting (CABG) due to epicardial injury and are not reliable indicators of myocardial ischemia in this setting. “However, ST elevation with reciprocal ST depression or other specific ECG patterns may be a more reliable finding of a potential ischemic event” (1). 1. While later on, ST-T changes can be secondary to pericardial/ epicardial inflammation and thus, can be non-specific (2), soon after completion of cardiac surgery they are probably more specific (3). At this stage, when the patient is still sedated and intubated, ST deviation can be an early marker of acute bypass failure or type 5 MI. Further studies are needed to evaluate the accuracy of routine 12-lead ECG after completion of surgery to detect ischemia/ infarction. 2. As the thresholds for cardiac troponin elevation for diagnosing MI are different for type 5 MI (>10 times the 99th percentile of the upper limit of normal) than for the other types of MI, it might be that different thresholds of ST deviation should be used in this scenario. As mentioned above, further studies are needed to clarify this issue. 3. Reciprocal changes are commonly seen in STEMI with ST elevation in the limb leads (inferior or lateral STEMI) (4). However, they are less common in anterior STEMI, especially when the left anterior descending (LAD) is occluded after the first diagonal branch (5). In our experience, acute MI caused by anastomosis failure or distal embolization of a graft to the LAD (usually the insertion is distal) normally does not cause reciprocal ST depression. ELECTROCARDIOGRAPHIC DETECTION OF MYOCARDIAL INFARCTION As stated, “The ECG is an integral part of the diagnostic workup of patients with suspected MI, and should be acquired and interpreted promptly” We disagree with the statement that “more profound ST-segment shifts or T wave inversion involving multiple leads/ territories are associated with a greater degree of myocardial ischemia…”. In our experience and based on the literature, T wave inversion in leads with an isoelectric ST segment does not occur with acute ischemia. It can be seen in the subacute phase or after reperfusion and should be regarded as “post-ischemic changes” (6). Negative T waves in leads with ST elevation are also seen after reperfusion or in the subacute phase of infarction. Only when seen in leads with ST depression can negative T waves signify acute subendocardial ischemia, or changes reciprocal to ST elevation in opposing leads. Therefore, we believe that T wave inversion should not be considered a sign of active ischemia It is written that “ST-segment depression ≥1 mm in 6 leads, which may be associated with ST segment elevation in leads aVR or lead V1 and hemodynamic compromise, is suggestive evidence of multivessel disease or left main disease”. However, in our opinion this statement should probably be restricted to patients in the appropriate clinical situation and to those with a relatively normal baseline ECG (7,8). In many patients with left ventricular hypertrophy, critical aortic stenosis, cardiomyopathy, left bundle branch block or nonspecific intraventricular conduction delay, dynamic diffuse ST depression associated with ST elevation in aVR can be seen. These changes can be more pronounced in patients with tachycardia or increased afterload. Implementation of the original statement could lead to over diagnosing NSTEMI in patients with positive cardiac markers secondary to hypertensive crisis or exacerbation of acute heart failure We think that the next statement is also questionable: “Prolonged new convex ST-segment elevation, particularly when associated with reciprocal ST-segment depression, usually reflects acute coronary occlusion and results in myocardial injury with necrosis.” The traditional literature emphasizes the “convex” pattern. Probably in the pre-reperfusion era when patients presented late (often with T wave inversion in the leads with ST elevation), the ST was often convex. However, nowadays, when patients present early, in a large percentage of patients the ST is concave (9). This is especially common in patients with anterior STEMI presenting early with ST elevation and tall positive T waves [Figure 1]. As mentioned above, reciprocal changes are commonly seen in inferior or lateral STEMI with ST elevation in the limb leads. However, they are less common in anterior infarct, especially when the LAD is occluded after the first diagonal branch. Yet, occlusion of a short LAD before the first diagonal branch is usually associated with ST elevation in aVL and reciprocal ST depression in the inferior leads. However, in the majority of patients with anterior STEMI, reciprocal ST depression is not seen [Figure 2]. “Reciprocal changes can help to differentiate STEMI from pericarditis or early repolarization changes”. Indeed, in both early repolarization and acute pericarditis, reciprocal changes are commonly seen only in aVR. Yet, in patients with left ventricular hypertrophy, cardiomyopathy and/or LBBB, “reciprocal” changes are common (ST elevation in V1-V2 with ST depression in I, aVL, V5-V6) (10). We believe that the cutoffs of ST segment elevation for the different leads (Table 2 in the FUDMI) should probably be limited to patients with narrow QRS and without voltage criteria for LVH (11). [ I introduced some of this in JECG 2004;37(Suppl): 98-103 and did say at that time that the criteria did not apply in the presence of LVH]. The thresholds for ischemic ST elevation in patients with LVH or cardiomyopathies have not been established (10) (11). Moreover, many patients with right bundle branch block (RBBB) display ST depression in leads V1-V3 at baseline. There are no established guidelines on how to diagnose acute inferolateral STEMI (ST depression in the anterior leads) in patients with complete or incomplete RBBB (12). In addition, it is unclear whether lower thresholds should be used for ST elevation in the anterior leads for diagnosing anterior STEMI in patients with complete or incomplete RBBB (12). It should be remembered that due to the way in which the six limb leads are derived, “reciprocal” changes within these leads are merely a function of the lead derivation, e.g. since aVR = -½(I + II), if there is ST depression in Leads I and II, then by definition, there must be ST elevation in avR. Simple mathematical considerations also show that ST elevation in aVL is reflected in ST depression in III and aVF so in a way these “reciprocal” changes in limb leads are “automatic” changes. While the text states that “upsloping ST-segment depression >1 mm at the J-point in the precordial leads” can be a sign of “significant left anterior descending artery (LAD) occlusion”, this pattern has not been included in Table 2 of the FUDMI. Upsloping ST depression is commonly seen during exercise stress tests and there is controversy regarding its significance. While initially it was considered a nonspecific pattern induced by tachycardia and not specific for ischemia, more recent studies have suggested that upsloping ST depression can be a true indicator of ischemia (13,14) (15,16). Upsloping ST depression with tall T waves in the anterior leads was described as an ECG sign of proximal LAD occlusion in patients presenting with chest pain (17,18). More recently, this pattern was described in 11 patients (0.2%) of 5,588 with suspected acute coronary syndromes whose ECG was transmitted by the field triage team. All of them had a culprit lesion in the proximal LAD (15,16). However, there are anecdotal descriptions of a similar pattern of upsloping ST depression with tall T waves in left circumflex ischemia (19-21) and even right coronary artery ischemia (22). Thus, we think that the description be changed to “significant coronary artery occlusion”, rather than LAD occlusion based on the current literature. It should also be noted that normal limits of ST elevation are race dependent (23). African and Chinese males, for example, have higher normal limits of ST elevation compared to Caucasians particularly in precordial leads. We think that allowance therefore has to be made for interpretation of ST shift particularly in Africans and Chinese. APPLICATION OF SUPPLEMENTAL ELECTROCARDIOGRAM LEADS The FUDMI recommends the use of “posterior leads at the fifth intercostal space (V7 at the left posterior axillary line, V8 at the left midscapular line, and V9 at the left paraspinal border)” for detecting ischemia caused by left circumflex occlusion. However, the original description of Wilson et al was that leads V6-V8 will be placed on a horizontal line from lead V4, rather than following the fifth intercostal space, (24) as used by Matetzky et al in the reference quoted by the FUDMI (25) and as described by the 2007 AHA/ACC/HRS Scientific Statement for the recommendations for the standardization and interpretation of the electrocardiogram (26). There is specific recommendation for recording these leads “in patients with high clinical suspicion of acute circumflex occlusion (e.g. initial ECG non-diagnostic or ST-segment depression in leads V1–V3)”. However, ST segment depression in leads V1-V3 is not suggestive of inferobasal myocardial ischemia. The RCA courses on the right atrioventricular groove, supplying branches to the right atrium and the free wall of the right ventricle, until the junction with the posterior interventricular groove. This can give a posterior descending artery that courses along the posterior interventricular groove and/or a posterolateral branch that supplies the inferolateral segments. The LCX courses on the left atrioventricular groove, until it reaches the posterior interventricular groove, supplying the left atrium and the free wall of the left ventricle via the obtuse marginal branches. The LCX may give rise to the left posterior descending artery that travels along the posterior interventricular groove. Thus, the majority of inferior infarcts due to RCA or LCX occlusion involve the basal inferior segment, unless the occlusion is in the mid or distal part of the posterior descending artery, sparing the basal segments. Cardiac MRIECG correlation suggested that it is correlated with the projection of the vector of inferior ischemia on the anterior-posterior plan (27). In the acute phase of STEMI, the reciprocal changes of ST elevation with positive T waves are ST depression with negative T waves. Therefore, in the acute stages of inferolateral STEMI with ST depression in V1-V3, the T waves are usually negative. Only after reperfusion, or with a more 27 Jia X, Heiberg E, Sejersten Ripa M, Engblom H, Carlsson M, Halvorsen S, Arheden H, Atar D, Clemmensen P, Birnbaum Y: Cardiac magnetic resonance evaluation of the extent of myocardial injury in patients with inferior st elevation myocardial infarction and concomitant st depression in leads v1-v3: Analysis from the mitocare study. Cardiology 2018;140:178. 28 Porter A, Vaturi M, Adler Y, Sclarovsky S, Strasberg B, Herz I, Kuzniec H, Birnbaum Y: Are there differences among patients with inferior acute myocardial infarction with st depression in leads v2 and v3 and positive versus negative t waves in these leads on admission? 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Am Heart J 2004;147:390. 36 Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van 't Hof A, Widimsky P, Zahger D: Esc guidelines for the management of acute myocardial infarction in patients presenting with st-segment elevation. Eur Heart J 2012;33:2569. Figure 1: a. A presenting ECG of a patient with anterior STEMI. There is concave ST elevation in V1-V6. There is a reciprocal ST depression in III and aVF. ’ Figure 1: b. Emergent coronary angiography shows tight lesion in the proximal left anterior descending (LAD) coronary artery. Figure 2: Anterior STEMI with ST elevation in I, aVL, V2-V6 without reciprocal ST depression.