A counterpoint paper : Comments on the electrocardiographic part of the 2018 Fourth Universal Definition of Myocardial Infarction endorsed by the International Society of Electrocardiology and the International Society for Holter and Noninvasive Electrocardiology

Ann Noninvasive Electrocardiol. 2020;00:e12786.   | 1 of 8 https://doi.org/10.1111/anec.12786 wileyonlinelibrary.com/journal/anec Received:31May2020 | Accepted:3June2020 DOI: 10.1111/anec.12786 REVIEW ARTICLE A counterpoint paper: Comments on the electrocardiographic part of the 2018 Fourth Universal Definition of Myocardial Infarction endorsed by the International Society of Electrocardiology and the International Society for Holter and Noninvasive Electrocardiology Yochai Birnbaum MD, FACC, FAHA1 | Miguel Fiol MD, PhD2 | Kjell Nikus MD, PhD3,4 | Javier Garcia Niebla RN5 | Ljuba Bacharova MD, DSc, MBA6,7 | Sergio Dubner MD8 | Wojciech Zareba MD, PhD9 | Peter W. Macfarlane DSc, eFESC, FRCP10 | Antonio Luiz Ribeiro MD, PhD11 | Iwona Cygankiewicz MD, PhD12 | Antoni Bayes de Luna MD, PhD, FESC, FACC13 1TheDepartmentofMedicine,TheSectionofCardiology,BaylorCollegeofMedicine,Houston,TX,USA 2Health Research Institute of the Balearic Islands, Hospital Son Espases, Palma, Spain 3Faculty of Medicine and Health Technology, Finnish Cardiovascular Research Center, University of Tampere, Tampere, Finland 4Heart Hospital, Tampere University Hospital, Tampere, Finland 5ServiciosSanitariosdelAreadeSaluddeElHeirro,ValledelGolfoHealthCenter,Frontera,Spain 6International Laser Center, Bratislava, Slovak Republic 7Institute of Pathophysiology, Medical School, Comenius University, Bratislava, Slovak Republic 8ClinicayMaternidadSuizoArgentinaandDeLosArcosSanatorio,BuenosAires,Argentina 9DivisionofCardiology,UniversityofRochesterMedicalCenter,Rochester,NY,USA 10ElectrocardiologySection,InstituteofHealthandWellbeing,UniversityofGlasgow,Glasgow,UK 11InternalMedicineDepartment,SchoolofMedicine,andTelehealthCenter,HospitaldasClínicas,UniversidadeFederaldeMinasGerais,BeloHorizonte,Brazil 12Department of Electrocardiology, Medical University of Lodz, Lodz, Poland 13Cardiovascular ICCCProgram, Research Institute Hospital de la Santa Creu i Sant Pau, Cardiovascular Research Foundation, Barcelona, Spain ThisisanopenaccessarticleunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsuse,distributionandreproductioninanymedium, provided the original work is properly cited. ©2020TheAuthors.Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC Correspondence Yochai Birnbaum, The Department of Medicine, Section of Cardiology, Baylor College of Medicine, One Baylor Plaza, MS BCM620,Houston,TX77030,USA. Email: [email protected] Abstract The Fourth Universal Definition of Myocardial Infarction (FUDMI) focuses on the distinction between nonischemic 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(a)detectingacuteischemia,(b)triage,and(c) riskstratificationuponpresentation.ThisreviewfocusesonmultipleaspectsofECG 2 of 8 | BIRNBAUM et Al. 1 | INTRODUCTION 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 nonischemic 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 (Thygesen et al., 2019). 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”(Thygesenetal.,2019).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. 2 | METHODS YB, MF, KN, JGN, and AB read the FUDMI and communicated about topics related to the ECG that should be discussed in this article. 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 article refer mainly to the original sections of the FUDMI (Thygesen et al., 2019). 3 | 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”(Thygesenetal.,2019). 1. While later on, ST-T changes can be secondary to pericardial/ epicardial inflammation and, thus, can be nonspecific (Borgaonkar & Birnbaum, 2019), soon after completion of cardiac surgery they are probably more specific (Liu & Birnbaum, 2019). 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) (Birnbaum, Sclarovsky, Mager, Strasberg, & Rechavia, 1993). However, they are less common in anterior STEMI, especially when the left anteriordescending(LAD)isoccludedafterthefirstdiagonalbranch (Birnbaum,Nikus,etal.,2014).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. interpretation that we firmly believe should be considered for incorporation in any future update to the Universal Definition of MI. KEYWORDS electrocardiography,epidemiology/clinicaltrials,non-invasivetechniques | 3 of 8 BIRNBAUM et Al. 4 | 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“postischemicchanges”(deLuna et al., 2014). Negative T waves in leads with ST elevation are also seen after reperfusion or in the subacute phase of infarction. Only 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.(b)Emergentcoronaryangiographyshowstightlesionintheproximalleftanteriordescending(LAD)coronary artery (a) (b) 4 of 8 | BIRNBAUM et Al. 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(Kim&Birnbaum,2013;Knotts,Wilson,Kim,Huang,& Birnbaum, 2013). 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 overdiagnosing 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 (Huang & Birnbaum, 2011). 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) (Birnbaum & Alam,2014). 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 (Macfarlane et al., 2004). [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(Birnbaum&Alam,2014)(Macfarlaneetal.,2004). 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 (Wei et al., 2013). 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 (Wei et al., 2013). 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,forexample,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 FIGURE 2 AnteriorSTEMIwithSTelevationinI,aVL,V2–V6 without reciprocal ST depression | 5 of 8 BIRNBAUM et Al. that upsloping ST depression can be a true indicator of ischemia (Polizos&Ellestad, 2006; Rijneke, Ascoop,& Talmon, 1980)(de Winter et al., 2019; de Winter, Adams, Verouden, & de Winter, 2016). 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(deWinter,Verouden, Wellens,&Wilde,2008;Veroudenetal.,2009).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(deWinteretal.,2019;deWinteretal.,2016).However, there are anecdotal descriptions of a similar pattern of upsloping STdepressionwithtallTwavesinleftcircumflexischemia(Alam, Nikus, Fiol, Bayes de Luna, & Birnbaum, 2019; Birnbaum, Wilson, etal.,2014;Misumida,Kobayashi,Schweitzer,&Kanei,2015)and even right coronary artery ischemia (Tsutsumi & Tsukahara, 2018). 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 (Macfarlane et al., 2014). African and Chinese males,forexample,havehighernormallimitsofSTelevationcompared with Caucasians particularly in precordial leads. We think that allowance therefore has to be made for interpretation of ST shift particularlyinAfricansandChinese. 5 | 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("RECOMMENDATIONSforstandardizationofelectrocardiographic and vectorcardiographic leads," Wilson et al., 1954) as used byMatetzkyetalinthereferencequotedbytheFUDMI(Matetzky etal.,1999)andasdescribedbythe2007AHA/ACC/HRSScientific Statement for the recommendations for the standardization and interpretationoftheelectrocardiogram(Kligfieldetal.,2007). There is specific recommendation for recording these leads “in patients with high clinical suspicion of acute circumflex occlusion (e.g., initial ECG nondiagnostic 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MRI-ECGcorrelationsuggestedthatitiscorrelatedwiththe projection of the vector of inferior ischemia on the anterior-posteriorplan(Jiaetal.,2018). 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 advanced stage of infarction, do the T waves become positive (reciprocal changes of ST elevation with negative T waves) (Porter et al., 1998). 6 | CONDUCTION DISTURBANCES AND PACEMAKERS The FUDMI states “In patients with LBBB, ST-segment elevation ≥1mmconcordantwiththeQRScomplexinanyleadmaybe anindicatorofacutemyocardialischemia.”Yet,thesensitivityofthis sign for STEMI physiology (acute occlusion of an epicardial artery) is low. We suggest that it be stated that since detection of ischemia by theECGinLBBBisdifficult,decisionsconcerningurgentreperfusion therapy should be based mainly on symptoms and hemodynamic parameters. According to the 2013 ACCF/AHA STEMI guidelines “NeworpresumednewLBBBhasbeenconsideredaSTEMIequivalent.”MostcasesofLBBBattimeofpresentation,however,are“not knowntobeold”becauseapriorECGisnotavailableforcomparison. New or presumed new LBBB at presentation occurs infrequently, may interfere with ST-elevation analysis, and should not be considered diagnostic of acute MIinisolation”(Jain etal.,2011;O'Gara et al., 2013). The European guidelines, published in 2017, specify “In thepresenceofLBBB,theECGdiagnosisofacutemyocardialinfarction is difficult but often possible if marked ST-segment abnormalitiesarepresent.Somewhatcomplexalgorithmshavebeenoffered to assist the diagnosis, but they do not provide diagnostic certainty. The presence of concordant ST-segment elevation (i.e. in leads with positive QRS deflections) appears to be one of the best indicators of ongoing MI with an occluded infarct artery. On the other hand, STdepression(usuallyconcordant)inV1–V3 in LBBB is very specific but not overly sensitive (Sgarbossa et al., 1996). Patients with a clinical suspicion of ongoing myocardial ischemia and LBBB should be managed in a way similar to STEMI patients, regardless of whether the LBBB is previously known. It is important to remark that the presenceofa(presumed)newLBBBdoesnotpredictanMIperse” (Ibanez et al., 2018). The FUDMI states “New, or presumed new, RBBB without associated ST-segment or T wave changes is associated with 6 of 8 | BIRNBAUM et Al. thrombolysis in myocardial infarction (TIMI) 0–2 flow in as many as 66% of patients (compared with > 90% in those with ST-segment or Twavechanges).”The2017ESCguidelinesforSTEMIalsospecify “Patients with myocardial infarction and RBBB have a poor prognosis. It may be difficult to detect transmural ischemia in patients with chest pain and RBBB. Therefore, a primary percutaneous coronary intervention strategy (emergent coronary angiography and percutaneous coronary intervention if indicated) should be considered whenpersistentischemicsymptomsoccurinthepresenceofRBBB” (Ibanez et al., 2018). These recommendations are mainly based on a retrospective study by Widimsky et al. (2012). These authors analyzed 6,742 patients with acute MI and found that among the 427 patients with RBBB (53% with concomitant ST elevation), TIMI flow 0 in the infarct-related artery was present in 51.7% and primary percutaneous coronary intervention was performed in 80.1% of the patients. TIMI flow 0 in the infarct-related artery was found in significantly more patients with new or presumed new RBBB (55%) than in the group with old RBBB 34.9%, old LBBB 28% or new or presumed new LBBB 41.1%. We think it should be stressed that these results apply to patients with adjudicated acute MI, rather than for the general population of patients presenting with acute symptoms. Moreover, the patients included in the study underwent cardiac catheterization, not necessarily emergent catheterization, as a part of a primary percutaneous coronary intervention protocol. Significant coronary artery lesions, including chronic total occlusion, can be found in patients with stable coronary artery disease and in those with non-ST-elevation acute coronary syndromes. Thus, coronary angiography can be recommended. However, as there are no data on outcomes with and without primary percutaneous coronary intervention in patients with chest pain and presumed new RBBB without ST deviation, the recommendation for emergent coronary angiography is probably overreaching. Recommending primary percutaneous coronary intervention for patients presenting with RBBB and with atypical symptoms (shortness of breath, acute heart failure, etc.) should be prospectively tested. A more recent study by Neumann et al. retrospectively assessed the significance of RBBB inpatientspresentingwithsuspectedmyocardialinfarction.Among 4,067 patients presenting with compatible symptoms, 125 patients (3.1%) had RBBB. Only 23 of them (18.4%) had a final diagnosis of acute MI (6 had STEMI and 17 NSTEMI). Yet, one-year mortality for patients with RBBB was 10.7%. They concluded that their data support the new ESC statement that RBBB is associated with a high risk of mortality; however, as the likelihood of acute MI was comparable tothatofthepatientswithoutRBBB,theyquestionedtheindication for emergent coronary angiography solely based on the presence of RBBB(Neumannetal.,2019).Inourexperience,diagnosingSTelevation in the inferior and lateral leads can easily be done in patients with RBBB. The problem, as discussed earlier, is how to diagnose inferolateralSTEMIequivalentinpatientswithRBBBandbaseline STdepressioninV1–V3 and whether the threshold for ST elevation intheanteriorleadsV1–V3 should be reduced. 7 | ADDITIONAL COMMENTS 7.1 | Reperfused STEMI Although the FUDMI does not directly deal with indications for acute reperfusion therapy, the entity of (spontaneously) reperfused STEMI is not mentioned in the documents nor in the STEMI guidelines(Ibanezetal.,2018;O'Garaetal.,2013).Patientswithspontaneous reperfusion at presentation (improvement in symptoms and ST-elevationresolutioncomparedwithapreviousECG)haveagood prognosis without primary percutaneous coronary intervention (de Lunaetal.,2014;Dowdyetal.,2004).Astheydonothaveongoing ischemia with progression of necrosis, coronary revascularization is indicated to prevent re-ischemia/ re-infarction, rather than salvaging myocardium. This can be done urgently, as in high-risk NSTEMI, rather than by using the time frame of primary percutaneous coronary intervention for acute STEMI. The most recent ESC STEMI guidelines from 2017 state “Early angiography (within 24 hr) is recommended if symptoms are completely relieved and ST-segment elevation is completely normalized spontaneously or after nitroglycerin administration (provided there is no recurrence of symptoms orST-segmentelevation).”Yet,thosewithresolutionofsymptoms and persistent ST elevation (despite having clear decrease in the magnitudeofSTelevationcomparedtotheoriginalECG)shouldbe treated according to this indication: “Reperfusion therapy is indicated in all patients with symptoms of ischemia of ≤ 12 hr duration and persistent ST-segment elevation” (Ibanez et al., 2018; O'Gara et al., 2013; Steg et al., 2012). This statement does not emphasize “ongoing”symptomsandthereforeincludespatientsinwhomsymptoms resolved but who continued to have ST elevation above the relevant threshold. We believe that thrombolytic therapy should not be administered to patients with spontaneous reperfusion despite having residual ST elevation, as the current recommendation states: “If timely primary PCI cannot be performed after STEMI diagnosis, fibrinolytic therapy is recommended within 12 hr of symptom onset in patients withoutcontraindications” (Ibanez etal.,2018; O'Gara et al., 2013; Steg et al., 2012). 8 | CONCLUSION Inconclusion,althoughtheECGhasbeenusedforthediagnosisand triage of patients with suspected myocardial infarction for many decades, many of the concepts and terminology currently used shouldbeupdated,asinotherfieldsofcardiologyandimaging.As new information is available, based on high-sensitive biomarkers, angiography, and especially cardiac magnetic resonance images, ourunderstandingofthesignificanceofthevariousECGpatterns continues to be refined. We recommend that these new concepts should be further studied and given due consideration for incorporation in any future guidelines. | 7 of 8 BIRNBAUM et Al. CONFLICT OF INTEREST The authors declare that they have no conflict of interest. AUTHOR CONTRIBUTIONS Allauthorsparticipateinwritingandeditingthemanuscript. ORCID Yochai Birnbaum https://orcid.org/0000-0001-7653-6328 Miguel Fiol https://orcid.org/0000-0002-5370-1391 Kjell Nikus https://orcid.org/0000-0002-9345-9851 Sergio Dubner https://orcid.org/0000-0001-9449-9225 Wojciech Zareba https://orcid.org/0000-0003-4146-420X Peter W. Macfarlane https://orcid.org/0000-0002-5390-1596 Antonio Luiz Ribeiro https://orcid.org/0000-0002-2740-0042 Iwona Cygankiewicz https://orcid.org/0000-0003-3006-311X Antoni Bayes de Luna https://orcid.org/0000-0003-1676-207X REFERENCES Alam,M.,Nikus,K.,Fiol,M.,BayesdeLuna,A.,&Birnbaum,Y.(2019). Upsloping ST depression: Is it acute ischemia? 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CIR.10.4.564 How to cite this article:BirnbaumY,FiolM,NikusK,etal.A counterpoint paper: Comments on the electrocardiographic part of the 2018 Fourth Universal Definition of Myocardial Infarction endorsed by the International Society of Electrocardiology and the International Society for Holter and Noninvasive Electrocardiology. Ann Noninvasive Electrocardiol. 2020;00:e12786. https://doi.org/10.1111/ anec.12786