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Journal of Electrocardiology 42 (2009) 1–5www.jecgonline.com

Editorial

Symposium on electrocardiogram in myocardial ischemia and infarction

The first recording of the electrocardiographic (ECG)pattern of acute myocardial infarction (MI), ST segmentelevation, was obtained by Eppinger and Rothberger1 afterintramyocardial injection of silver nitrate in 1909. Smith2

reproduced this finding by ligation of the left circumflexcoronary artery in 1918. Pardee was the first to publish apatient case with ST elevation described as a T wave starting“from a point well up on the descent of the R wave.”3 Thetypical sequential ECG signs of occlusion of an epicardialartery are well known today: the T wave becoming tall andpeaked, followed by elevation of the ST segment (the “injurypattern”), followed by changes in the initial portion (Qwaves) and terminal portion (increase in R wave amplitudeand decrease in S wave amplitude) of the QRS complex.However, in the modern era of sophisticated diagnostic andtherapeutic modalities, electrocardiography has been some-what neglected. This is partially because of the impressionthat the data obtained by ECG is indirect and many timesinaccurate. It is conceived that the newer noninvasiveimaging modalities are more accurate and give more directinformation. However, careful analysis of these modalitiesshows that their use at the presenting phase of acutecoronary syndromes (ACS) is impractical; since mostpatients present to hospitals lacking the expertise inperforming sophisticated imaging modalities 24 hours aday. Furthermore, in many cases the patients are having painand/or shortness of breath and, therefore, cannot hold theirbreath for a long time, a prerequisite for cardiac computedtomographic angiography, or cannot lay flat and still,making echocardiography and radionuclear or magneticresonance imaging difficult or impossible. Thus, althoughthe newer modalities have the potential to better delineatethe size and location of the ischemic area at risk, there hasbeen only few studies reporting on the use of thesemodalities in the acute stage of MI.

The size and site of the final infarction does notnecessarily correlate with the size and location of theischemic area at risk, especially in patients undergoingprompt reperfusion therapy. However, only few studiescorrelating the ECG patterns in the acute stage of infarctionwith imaging of the ischemic area at risk have beenpublished. Most of our information has been derived fromstudies correlating ECG patterns with coronary angiographicfindings. However, it is clear that in many cases, theischemic area at risk does not correlate with the “potential

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ischemic area at risk;” that is the situation when the coronaryartery was occluded at the site of the thrombus. In manycases the thrombus overlying the culprit lesion is not totallyocclusive and the actual ischemia is caused by distalembolization to more peripheral branches. For example, athrombus in the left main coronary artery may cause STelevation in leads V5 to V6 due to distal embolization toperipheral coronary artery branches.

Without doubt, the ECG is the most useful and feasibletool for the initial evaluation, early risk stratification, triage,and guidance of therapy in patients with a suspicion of anacute ischemic event. Especially in ST-elevation ACS, theECG from the acute phase contains important informationabout the site and size of the area at risk aiding in selectionof appropriate therapy for the individual patient.4,5 How-ever, the anatomic, pathophysiologic, and prognosticinformation contained in the “simple” 12-lead ECG is notoptimally used in routine clinical work. One way towardmore optimal implementation of the diagnostic informationin the ECG to improve patient care is usage of regionallogistic telecardiology systems for “on-line” expert evalua-tion. Optimally, these systems should include immediateaccess to digitally stored ECGs to compare actual recordingswith previous ones. From a technical perspective, referenceECGs could be made available anywhere and anytime at thevery onset of an acute coronary event through Internet-basedtelemedicine.6 Equally important is continuous education ofhealth care personnel, which is also one of the aims of thismini-symposium.

Morphologic ECG interpretation

Use of the ECG to predict the culprit artery, and even thelocation of the culprit lesion within the infarct-related artery,could provide clinically important information to augmentdecision making and tailor reperfusion therapy. Electro-cardiographic criteria for prediction of culprit lesion location(proximal vs distal) are primarily based on the principle factthat involvement of major side branches in the ischemic areachanges the “injury” vector in a predictable manner.5

Especially in geographic regions with long transportdistances, individual risk stratification based on clinicalfindings and ECG data about the estimated size of the area atrisk and the severity of the ischemic process can help inchoosing appropriate therapeutic strategies.7

2 Editorial / Journal of Electrocardiology 42 (2009) 1–5

Wang et al8 studied consecutive patients referred from theemergency department (ED) for emergent coronary angio-graphy, and using ECG criteria derived from previousstudies, attempted to predict the culprit lesion. Their criteriacorrectly identified left main, proximal left anterior descend-ing (LAD) or proximal right (RCA) culprit lesions with apositive and negative predictive value of 72% and 81%,respectively. The authors concluded that recognizing theECG criteria for such lesions has the potential for shorteningdoor-to-reperfusion time and improving patient outcomes.The relatively low positive predictive value for proximalRCA occlusion (64%) may be explained by the ECGcriterion used by the authors being electro/pathophysiologi-cally illogical. Indeed, ST elevation in lead III higher than inlead II in conjunction with ST depression in leads I and aVLis typical for right coronary artery occlusion. However, inproximal RCA occlusion, involvement of the right ventricletends to attenuate ST depression in leads V1 to V2.Therefore, presence of ST depression in these leads pointsagainst, not in favor of, proximal RCA occlusion (Table 1 ofWang et al in this issue). It is hoped that a large prospectivestudy to test different ECG criteria for culprit artery andlesion location will be performed in the near future.

Zhong-qun et al9 in this isuue present 2 cases with acuteanterior ST-elevation myocardial infarction (STEMI) anddiscuss the background of the so-called extensive anteriorSTEMI, including ST elevation in leads V1 through V6. Inanterior STEMI, the ECG is useful to predict LAD occlusionsite in respect to major side branches. In general, moreproximal lesions indicate larger area at risk. Lead aVR STelevation has been associated with an occlusion proximal tothe first septal branch, whereas ST elevation in leads I andaVL has been linked to prediagonal culprit lesions. Lead V1

represents the electrical activity of the right paraseptal region.A large conus branch of the right coronary artery may supplythe right paraseptal region. In these individuals, this regionhas a dual blood supply, and accordingly, proximal LADocclusion may not cause ST elevation in lead V1. As pointedout by Rakita et al10 in this issue, the precordial leads V1 andV6 often face almost opposite aspects of the heart; STelevation in V1 is often accompanied by ST depression in V6.Hence, in proximal LAD occlusions, which mostly involvealso the LV apex, ST elevation is not necessarily present inleads V5 and V6, due to cancellation of anatomically opposite“injury” vectors. The authors suggest that the extensiveanterior STEMI pattern with ST elevation in both V1 and V6

could be present in cases with a distal LAD occlusion in alarge “wrap-around-the-apex” LAD especially in patientswith a small conus branch. ST elevation in lead V1 would becaused by the small conus branch (no protection of the rightparaseptal area), but the basal septum would not necessarilybe involved in the ischemic process. Hence, apical transmuralischemia, indicated by ST elevation in V5 and V6, would notbe counteracted by basal septal transmural ischemia. The casereport challenges the common knowledge that the size of theischemic area at risk and/or final infarct size correlates withthe number of leads with ST elevation or the sum of STelevation, highlighting the importance of cancellation of the“injury” vectors by opposing zones, such as lack of ST

deviation in the anatomically opposite leads aVL and III inpatients with proximal occlusion of a wrap-around LAD or inproximal occlusion of a dominant left circumflex coronaryartery. Their explanation also challenges an alternativeexplanation by Sclarovsky5 in this issue that lack of STelevation in the anterolateral leads in LAD occlusion isrelated to alternative blood supply to the anterolateral andapical regions by big diagonal branches originating proximalto the LAD occlusion, or alternatively, by developed obtusemarginal branches and/or ramus intermedius. Thus, furtherstudies are needed to assess the significance of the differentand distinct patterns of the classic subclassification of STEMI(anteroseptal, anterolateral, extensive anterior, etc).

Madias,11 a colleague with knowledge of practically allaspects of the ECG, presents an editorial in this issue inwhich he places the works of 2 distinguished ECG expertgroups, the Prinzmetal and the Sclarovsky groups, intohistorical perspective. He finds some similarities of theworks by the 2 groups, although the medical communitychanged considerably during the decades that separate thegroups in time. The author notes that both groups ofinvestigators gleaned what was important in the work of theirpredecessors, put together a working model for theirinvestigations, and proceeded to explore this model in newscientific ventures. As a background, Madias also brieflydescribes the work by the “OldMasters” of ECG in ischemia.In his article, the author criticizes the use of dichotomizingthe continuous ECG changes into 3 “grades,” as statisticiansand epidemiologists discourage this approach. However, inclinical practice, we commonly dichotomize continuousvariables into “grades” and “stages” (eg, New York HeartAssociation class for heart failure, severity of valvulardisease, stages of cancer). Thus, pure academicians andepidemiologists may use different approaches to analyzecontinuous variables.

In a responding editorial, Sclarovsky5 gives a briefpresentation of the scientific work by he and his group in thefield of acute myocardial ischemia. In the pre-thrombolyticera, Sclarovsky and his group systematically studiedthousands of consecutive patients in the Intensive CardiacCare Unit by continuous recording of the ECG, acquiringnew insight into different types of ischemic syndromes, andreperfusion patterns. Imaging modalities, like echocardio-graphy and coronary angiography opened new views into thetopics of interest. During almost 3 decades, the Sclarovskygroup contributed extensively to our understanding of theanatomic, pathophysiologic, and prognostic information ofthe ECG, both in ST elevation– and ST depression–relatedACS. Also, the concept of grading the severity of myocardialischemia was introduced. Now, finally, new aspects of thebasis for ECG changes are introduced by the author from therapidly expanding field of molecular biology. His theories,which are based on unique clinical experience combinedwith extensive knowledge of the literature, should be studiedin appropriate experimental and clinical models. Simplequestions, such as prognostication based on the severity ofischemia (grades of ischemia) and the size of the ischemicarea at risk (patterns of ST elevation) should be tested inlarge randomized trials.

3Editorial / Journal of Electrocardiology 42 (2009) 1–5

In an animal study, Floyd et al12 in this issue analyzed theimpact of preconditioning and collateral flow, as methods ofmyocardial protection, both on ST elevation and QRS complexprolongation during repeated episodes of the dominant leftcircumflex artery occlusion. Collateral flow was measured byinjection of radioactive microspheres. The authors found areduction of both ST elevation and QRS complex prolongationby the presence of collateral flow and ischemic preconditioning.The limitations of this study are that it is composed ofretrospective analysis of ECGs from experiments conducted inopen chest dogs before 1990 and data were analyzed only fromlead II. As mentioned by Sclarovsky,5 ECG tracings aredistorted in open chest animals, and although lead II recordedby the investigators may be adequate to monitor inferior wallischemia in close-chest humans, it is unclear whether this leadrepresents the maximal ischemic changes due to dominant leftcircumflex occlusion in the open-chest dog.

The significance of ST changes before, during, and afterreperfusion therapy

Early ST-segment resolution after reperfusion therapy isassociated with microvascular reperfusion and improvedoutcome. The number of studies evaluating the significanceof ST changes before and during reperfusion therapy islimited. In the thrombolytic era, re-elevation of the STsegment was reported both as a marker of successfulreperfusion and a marker of reperfusion injury. Less isknown about the significance of changes in the magnitude ofST elevation before and during invasive therapy. Terkelsen etal13 add to our knowledge of the significance of ST changesin acute STEMI. In this issue they show that spontaneous (oraspirin/heparin-induced) ST resolution before primary per-cutaneous coronary intervention (PCI) predicts minimal finalinfarct size, whereas intervention-related increase in STelevation predicts extensive final infarct size; supporting theconcept that intervention-induced increase in ST elevationmay signify reperfusion injury or distal embolization of theocclusive thrombus plugging small vessel branches.Although not directly addressed in their article, this studydepicts the complexity of defining ST resolution; should weuse sum of ST elevation, the sum of all ST deviation, or themagnitude of ST deviation in the lead with maximal STelevation in the presenting ECG? As a thrombus may shiftand migrate downstream, side branches may recanalize orocclude especially during thrombolytic therapy or PCI; thepattern of ST elevation may shift and thus may alter the sumof ST elevation and/or the magnitude of ST elevation inindividual leads. For example, if Zhong-qun et al9 arecorrect, distal migration of a proximal LAD thrombus duringPCI may cause an increase in ST elevation in lead V6 and the“inferior” leads (especially if the LAD is wrapping aroundthe ventricular apex). Moreover, this study depicts theproblem of where to measure the ST segment. This subjectwas addressed in the present issue by Rekik et al.14 Terkelsenet al measured the ST halfway between the J point and thestart of the ST segment. Is this point affected by concomitantdynamic changes in T waves? As pointed out bySclarovsky,5 tall T waves in the early “preinfarction” stage

may signify epicardial protection, whereas early inversion ofthe T wave is considered as a sign of reperfusion.

Rekik et al14 in this issue present an article related to totalabsence of ST resolution after failed thrombolysis. Whencomparing with the ST-segment elevation before thrombo-lytic therapy, they found that absence of ST resolution 90minutes after therapy compared with partial (10%-50%) STresolution was associated with hemodynamic deterioration,inferior epicardial coronary artery blood flow, and multi-vessel disease, despite similar post-rescue PCI ST resolution.In multivariate analysis, total absence of ST resolution wasan independent predictor of in-hospital mortality and long-term major adverse cardiac events. This study actuallychallenges the strong association between ST resolution andrestoration of myocardial tissue perfusion or viability, asboth patient groups had similar rates of ST resolution afterPCI yet different short- and long-term outcomes.

Predicting acute coronary syndrome in the ED usingonly the ECG

The correct identification of ACS in patients with chestpain is a major challenge in the ED. Failure to admit patients,who subsequently prove to have an acute event caused bycoronary artery disease, may result in a new coronary eventwith potential for sudden death within the next few days orweeks. As no diagnostic strategy has yet been proven reliableto identify all cases of ACS, admission to “rule out ACS” isoften used. However, 7 of 10 patients prove not to have ACS,posing economic burden on the medical community. TheECG is the single most important method to predict ACS inthe ED. Forberg et al15 in this issue compared the ACSprediction abilities of 4 different ECG diagnostic methods inED patients presenting with chest pain. The investigators'artificial neural network and multivariable logistic regressionmodel were superior to expert interpretation and classic ECGcriteria to predict ACS. The authors state that most of theACS predictive information currently available in the ED canbe found in the ECG. Their logistic regression model whichperformed best, included parameters from the QRS complex,the ST segment and the T wave, well known to be the mostimportant ECG parameters in acute ischemia. The positivepredictive value and the negative predictive value for ACSwere 35% and 98%, respectively, indicating that the datafrom the ECG only are not enough to make decisions aboutpatient discharge or admission. It should be remembered thatin many patients with non-STEMI or unstable angina, theischemia is transient; and if the ECG is recorded when thepatient is symptom-free, ischemic changes may not bedetected; although occasionally the footprints of the previousischemia (negative Twaves) may be seen. This fact points tothe importance of ECG recording during episodes ofsymptoms and to the comparison with previous or follow-up ECG recordings when the patient is symptom-free.Telemedicine systems with immediate 24/7 access toprevious ECGs and continuous ECG monitoring have thepotential to improve decision making. Knowledge of patienthistory, such as existence of structural heart disease, riskfactors for coronary artery disease, and presenting

4 Editorial / Journal of Electrocardiology 42 (2009) 1–5

symptoms, are important. Adding results of biomarker testsand in certain cases, echocardiography, will help in decisionmaking. In acute STEMI, one should not await results ofbiomarker tests but decide on reperfusion therapy based onthe ECG, symptoms, and clinical findings. It should bementioned that some of the criteria, used by Forberg et al, todefine unstable angina are unusual. For example, acute heartfailure or pulmonary edema with transient or persistent STdepression without changes in the Q and R waves. Thesemay occur in hypertensive heart disease with repolarizationchanges and not necessarily indicate unstable angina. In ouropinion, some of the ECG criteria found to be associated withACS are related to the likelihood of preexisting coronaryartery disease but do not necessarily represent acutemyocardial ischemia; to mention one example, negativeQRS area in lead avF (Table 2 in their article). Also, anegative T wave in lead V2 is found in children and youngwomen and may not by itself be a sign of ischemia.

ST-segment changes and temporal relation to the J pointduring heart rate increase

There is a controversy where to measure the ST segment.Studies that considered exercise stress tests suggested that STshould be measured at the J point + 60 or 80 milliseconds, asdepression of the PR segment may affect the STsegment duringtachycardia and cause up-sloping ST depression. Indeed, up-sloping ST depression during an exercise stress test is notconsidered to reflect ischemia. However, for STEMI, it isrecommended to measure the STat the J point, as changes in theTwavemay affect themagnitude of ST if measured late after theJ point. If the ST is measured at J + 80 milliseconds, manyindividuals without structural heart disease have N0.2 mV STelevation in the precordial leads. In the present issue Haney etal16 studied the relation between different J point intervals to ST:J point, J + 20 milliseconds, J + 60 milliseconds, and J + 80milliseconds, during pacing-induced tachycardia in patientsknown to have coronary artery disease with a positive exercisetest. The patients were investigated during general anesthesiawhile being prepared for bypass surgery. The ST-segmentchanges increased in a similar fashion during pacing-inducedischemia. Therewas no significant difference in ST results whenmeasurements were performed at different time intervals.However, the authors do not mention if their pacing inducedSTelevation or depression.Moreover, as stated by the authors, itis unclear whether their findings are applicable to exercise stresstests. The authors mention that in some situations, it is verydifficult to identify the J point. In these cases, measurement ofST at the J point may indeed be difficult but that should alsoaffect measuring ST at fixed intervals after the J-point.

Risk stratification post-MI

Giannospoulis et al in this issue studied the predictive valueof the spatial QRS-T angle (angle between the maximal spatialQRS and T vectors) circadian variation with 24-hour, 12-leadambulatory digital ECG recording before hospital discharge inpost-MI patients.17 Inverse QRS-T angle circadian pattern,defined as lower values during the day than during the night,

was found to be associated with adverse outcome, whereas anormal pattern (lower values during nighttime) was associatedwith a favorable outcome. As pointed out by the authors, theQRS-T angle is different between sexes, and post-MI patientshave altered autonomic tone.Hence, the findings by the authorscould be explained by severe disruption of normal autonomicfunction and hormonal circadian cycles in post-MI patients athigher risk of adverse outcome.Confirmation in larger prospec-tive studies is needed before the spatial QRS-T angle circadianvariation possibly could be added to the list of noninvasive riskmarkers in post-MI patients. One potential advantage of themethod is the fact that the prognostic information seems to bepresent already a few days after the index event.

QRS scores to quantifymyocardial infarction and fibrosis

In the present issue, Strauss et al18 describe the QRScomplex as a biomarker that images the heart. They present ahistorical overview starting from the legendary work bySmith in 1918 after ligating coronary arteries in dogs.2 Theypresent the Selvester QRS MI score in detail, includingclinical utility. New methods of QRS scoring in the presenceof all types of ventricular conduction, including hypertrophyand fascicular and bundle branch blocks-, are presented.These QRS scores were developed by simulating MIthroughout the left ventricle in each conduction type. Earlierstudies, using predischarge technetium sestamibi SPECTscans, concluded that in patients receiving reperfusiontherapy, the correlation between the predischarge SelvesterQRS score and the perfusion defect size was poor. However,it might be that these scans overestimated the necrotic zone.Validation in small studies has been performed using cardiacmagnetic resonance imaging as the gold standard for finalinfarct size, but larger multicenter magnetic resonanceimaging studies are needed for proper validation. Postmor-tem anatomical studies are probably not necessary becauseof the new potential “golden standard.”

Acoustic cardiography during PCI

Hemodynamic changes may be induced by ischemia beforeany symptoms or ECG changes. Lee et al19 in the present issueproposed that computerized acoustic cardiography as anoninvasive test might prove to be a useful diagnostic tool incombination with ECG data to diagnose acute myocardialischemia. During PCI-induced ischemia, a new or increasedintensity third or fourth heart sound was detected in about 2 of 3patients. Interestingly, in 10 of 15 patients without ST criteriafor ischemia, new or increased-intensity diastolic heart soundswere recorded. The method needs evaluation in patients withand without clinical ischemia.

The studies in this symposium depict the complexityof investigating the ECG changes in patients with ACS. Newideas and methods are published, and their findings shouldbe validated in independent multicenter randomized trials. Itis hoped that this mini-symposium adds to the knowledgeof the medical community dealing with patients withacute myocardial ischemia and also stimulates furtherresearch in the field.

5Editorial / Journal of Electrocardiology 42 (2009) 1–5

Kjell C. NikusHeart Center, Department of Cardiology

Tampere University HospitalTampere, Finland

E-mail address: kjell.nikus@pshp.fi

Yochai BirnbaumThe Department of Medicine, Section of Cardiology

Baylor College of MedicineHouston, Texas, USA

E-mail address: ybirnbau@bcm.edu

References

1. Eppinger H, Rothberger CJ. Zur Analyse der Electrokardiogramms.Wien klin Wochnschr 1909;22:1091.

2. Smith FM. The ligation of coronary arteries with electrocardiographicstudy. Arch Intern Med 1918;22:8.

3. Pardee HEB. An electrocardiographic sign of coronary artery obstruc-tion. Arch Intern Med 1920;26:244.

4. Birnbaum Y, Drew BJ. The electrocardiogram in ST elevation acutemyocardial infarction: correlation with coronary anatomy and prog-nosis. Postgrad Med J 2003;79:490.

5. Sclarovsky S. Upgrading the ECG toward the 21 century. J Electro-cardiol 2009;42:35.

6. Fayn J, Rubel P, Pahlm O, Wagner GS. Improvement of the detection ofmyocardial ischemia thanks to information technologies. Int J Cardiol2007;120:172.

7. Nikus KC, EskolaMJ, Niemelä KO, Sclarovsky S.Modernmorphologicelectrocardiographic interpretation—a valuable tool for rapid clinicaldecision making in acute ischemic coronary syndromes. J Electrocardiol2005;38:4.

8. Wang SS, Paynter L, Kelly RV, Koch GG, Skains MS, Gettes LS.Electrocardiographic determination of culprit lesion site in patients withacute coronary events. J Electrocardiol 2009;42:46.

9. Zhong-qun Z, et al. Does left anterior descending coronary artery acuteocclusion proximal to the first septal perforator counteract ST elevationin leads V5 and V6? J Electrocardiol 2009;42:52.

10. Rakita L, Borduas JL, Rothman S, Prinzmetal M. Studies on themechanism of ventricular activity. XII. Early changes in the RS-Tsegment and QRS complex following acute coronary arteryocclusion: experimental study and clinical applications. Am HeartJ 1954;48:351.

11. Madias J. Prinzmetals' work and the “Sclarovsky-Birnbaum ischemiascore” for acute myocardial infarction: a parallel in systematizingelectrocardiographic knowledge. J Electrocardiol 2009;42:27.

12. Floyd J, et al. Effect of ischemic preconditioning and arterialcollateral flow on ST-segment elevation and QRS complex prolonga-tion in a canine model of acute coronary occlusion. J Electrocardiol2009;42:19.

13. Terkelsen CJ, et al. ST changes before and during primary percutaneouscoronary intervention predict final infarct size in patients with STelevation myocardial infarction. J Electrocardiol 2009;42:64.

14. Rekik S, et al. Total absence of ST-segment resolution after failedthrombolysis is correlated with unfavourable short- and long-termoutcomes despite successful rescue angioplasty. J Electrocardiol2009;42:73.

15. Forberg J, et al. In search of the best method to predict acute coronarysyndrome using only the electrocardiogram from the emergencydepartment. J Electrocardiol 2009;42:58.

16. Haney M, et al. ST changes and temporal relation to the J pointduring heart rate increase and myocardial ischemia. J Electrocardiol2009;42:6.

17. Giannospoulis G, et al. Prognostic significance of inverse spatial QRS-Tangle circadian pattern in myocardial infarction survivors. J Electro-cardiol 2009;42:79.

18. Strauss DG, et al. The QRS complex—a biomarker that “images” theheart: QRS scores to quantify infarction and fibrosis in all types ofventricular conduction. J Electrocardiol 2009;42:85.

19. Lee E, et al. Frequency of diastolic third and fourth heart sounds withmyocardial ischemia induced during percutaneous coronary interven-tion. J Electrocardiol 2009;42:39.