The ST-segment elevation (STE) myocardial infarction (MI)/non-STEMI (NSTEMI) paradigm has been the central dogma of emergency cardiology for the last 30 years. Although it was a major breakthrough when it was first introduced, it is now one of the most important obstacles to the further progression of modern MI care. In this article, we trace why a disease with an established underlying pathology (acute coronary occlusion [ACO]) was unintentionally labeled with a surrogate electrocardiographic sign (STEMI/NSTEMI) instead of pathologic substrate itself (ACO-MI/non-ACO-MI or occlusion MI [OMI]/non-OMI [NOMI] for short), how this fundamental mistake caused important clinical consequences, and why we should change this paradigm with a better one, namely OMI/NOMI paradigm.
Keywords: Acute coronary syndrome, coronary occlusion, electrocardiogram, myocardial infarction, ST-segment elevation
| Introduction|| |
The ST-segment elevation (STE) myocardial infarction (MI)/non-STEMI (NSTEMI) paradigm has been the central dogma of emergency cardiology for nearly 30 years. It has been widely accepted as the infallible indication of an acute coronary occlusion (ACO) or near-occlusion that necessitates and benefits from immediate reperfusion. The term STEMI established itself so firmly in our minds, as if the real disorder that we are looking for was an electrocardiogram (ECG) abnormality rather than the ACO itself. If the ECG does not show STE despite the subsequent angiogram showing an ACO, the STEMI/NSTEMI paradigm automatically accepts it as a NSTEMI, not a missed “STEMI.” This highly presumptuous, yet widely accepted, claim with “no false negativity” is a quite uncommon, if not unique, diagnostic paradox in medicine. As a consequence, it is falsely reassuring as if it is acceptable to let a patient actively have an MI under our supervision as long as there is no “diagnostic” STE on the ECG. Consequently, the validity of the established STEMI/NSTEMI paradigm started to be questioned, and the need for better paradigm has unavoidably risen.,,
In this article, we trace why a disease with an established underlying pathology (ACO) was unintentionally labeled with a surrogate ECG sign (STE) instead of pathologic substrate itself (ACO-MI/non-ACO-MI or OMI/non-OMI [NOMI] for short), how this fundamental mistake caused important clinical consequences, and why we should change this paradigm with a better one, namely OMI/NOMI paradigm.
| What Is a ST-Segment Elevation Myocardial Infarction?|| |
The notion that the STEMI patients would benefit from emergent reperfusion therapies comes from fibrinolytic studies done in the 1990s. In these trials, patients with suspected ACO, mostly without an evidence of STE or the presence of angiographic ACO being sought, had been randomized to fibrinolytics versus placebo and mortality had been taken as the outcome measure. Pooled data from these trials were studied in the seminal fibrinolytic therapy trialists' meta-analysis, which showed an impressive reduction in mortality with a slightly better benefit in patients with (ambiguously and inconsistently defined) STE compared to general cohort. This was an unparalleled revolution in cardiology which made “reperfusion medicine” the norm.
However, as many patients with no ACO, as well as normal subjects, have some STE on their ECGs, this vague STE needed to be defined better. Menown et al. compared STE in normal subjects and patients with creatine kinase- MB (CK-MB)–diagnosed MI (again without referencing to ACO) and found that ≥2 mm STE in at least one of the anteroseptal leads or ≥1 mm in any of the other leads differentiates patients with MI from normal subjects. These results provided the basis for the first universal definition of MI. Later, Macfarlane et al. fine-tuned these criteria introducing age- and sex-based cutoffs, again comparing CK-MB–positive patients with normal subjects and without including any angiographic outcomes. In 2009, American Heart Association, American College of Cardiology Foundation, and Heart Rhythm Society took these cutoffs that were originally developed to differentiate CK-MB–positive MI patients with normal subjects and surprisingly recommended their use in the differentiation of patients with STEMI and NSTEMI. These “STEMI criteria,” namely (1) 1 mm STE in any two contiguous leads except V2 and V3; (2) STE in V2 and V3 on the basis of age and gender, where the following cut-points apply: ≥1.5 mm elevation in women regardless of age, ≥2.5 mm in men aged less than 40 years, and ≥2 mm in men aged 40 years and above, stuck and were repeated throughout the future guidelines, including the latest universal definition of MI consensus.
| Can a Non-ST-Segment Elevation Myocardial Infarction Still be OMI-nous ?|| |
Although the current guidelines prudently advocate urgent (<2 h) invasive assessment in patients with persistent pain, hemodynamic compromise, acute heart failure, and/or arrhythmias to identify high-risk patients that may benefit from urgent revascularization, it is not clear if this recommendation aims to identify high-risk patients or the patients with ACO. This distinction is highly relevant because high-risk patients may not necessarily benefit from urgent revascularization procedure despite having an increased short-term mortality; however, in the latter situation, urgent revascularization is expected to have a positive effect on the outcomes.
Observational studies indeed show that the current STEMI criteria miss approximately one-third of ACOs.,,,,,,,, This suggests that, when STEMI criteria are not met, the physicians do not manage to identify the patients with ACO among all patients with undifferentiated persistent chest pain partly because it may be present in many other competing diagnoses., Furthermore, STEMI criteria were shown to have only a prospective sensitivity of 21% and 49% for ACO when a computer algorithm and cardiologist evaluation were used, respectively. Physicians across different specialties have poor accuracy and poor interrater reliability for detecting ACO and cannot even agree on where and how to measure the STE.,
A high percentage of coronary occlusion at the 24-h angiogram was also seen in the randomized trials on acute management of NSTEMI comparing early and late intervention, even after the patients with persistent pain were excluded.,,, Therefore, the presence or the absence of persistent pain, hemodynamic compromise, severe heart failure, and/or arrhythmias are not reliable indicators for diagnosing or excluding an OMI; hence, clinicians need to put all lines of evidence together. Moreover, a recent real-life study showed that the clinicians generally do not elect to use urgent coronary angiography in the presence of these clinical parameters.
On the other hand, the group of patients labeled as NSTEMI but having ACO is deprived of emergent reperfusion therapy, succumbs larger infarcts, and is roughly 1.5 times higher short- and long-term risk mortality.,,,,, Although no study compared early versus late intervention in patients with OMI, NSTEMI, observational evidence suggests that these patients significantly benefit from early intervention.,
| What Is an Occlusion Myocardial Infarction?|| |
OMI is an ongoing MI due to a total or near-total coronary occlusive process that necessitates acute reperfusion. It has no ECG, echocardiographic, or even angiographic findings in its definition (as coronary occlusion may spontaneously reperfuse at the time of the angiogram, so the absence of angiographic occlusion does not exclude an OMI). It reminds the clinician that even if the ECG is nondiagnostic, the patient may still need acute reperfusion, and therefore, active search for further evidence should be warranted.
Three studies especially worth mentioning for supporting how such an endeavor seems rewarding. The DIagnostic accuracy oF electrocardiogram for acute coronary OCClUsion resuLTing in MI (DIFOCCULT) study retrospectively compared OMI/NOMI approach with STEMI/NSTEMI paradigm. As expected, 28.2% of the patients initially classified as having NSTEMI were reclassified by the ECG reviewers as having OMI. This subgroup had a higher frequency of ACO, myocardial damage, and both in-hospital and long-term mortality compared to the NOMI group. The OMI/NOMI approach to the ECG had a superior diagnostic accuracy compared to the STE/NSTEMI approach in the prediction of both ACO and long-term mortality. Furthermore, early intervention in patients with OMI-predicting ECGs was associated with lower long-term mortality, whereas early intervention increased long-term mortality in patients with NOMI-predicting ECGs.
Another retrospective case–control study compared the accuracy of STEMI criteria versus structured OMI interpretation by expert ECG reviewers. The OMI approach to ECG had significantly higher sensitivity (86% vs. 41% and 80% vs. 36%) for the detection of ACO compared to the STEMI criteria. The patients classified as NSTEMI, but OMI had a similar infarct size measured by peak troponin but greater delays to angiography compared with the patients classified as STEMI and OMI. Moreover, OMI approach diagnosed ACO earlier with a median of 1.5 h compared to STEMI approach.
Another study by the same group compared the STEMI/NSTEMI versus OMI/NOMI paradigms in 467 consecutive high-risk acute coronary syndrome patients. Among the 108 patients with OMI, only 60% had any ECG fulfilling STEMI criteria. NSTEMI but OMI patients had similar infarct sizes and adverse outcomes as compared with the STEMI and OMI patients but were much less likely to receive emergent catheterization.
In summary, many studies indicated that the ECG has the capability of recognizing ACO with high accuracy beyond mere STE, including minor STE not fulfilling STEMI criteria, STE disproportionate to corresponding QRS-T-QT complex, unusual patterns with contiguous leads showing opposite ST-segment deviations, and some patterns not showing STE at all, but that a compilation of ECG tools will inevitably be necessary for diagnosis rather than using a single set of STEMI millimeter criteria.,,, The readers strongly advised to refer to our latest article which provides a step-by-step approach to OMI diagnosis. Furthermore, the diagnosis of ACO is not limited to ECG. The use of other diagnostic tools, such as echocardiography,, computed tomography angiography, and conventional angiography, should be considered when clinical suspicion is high.
| Conclusion|| |
The current STEMI/NSTEMI paradigm is imperfect and needs to be replaced by a better OMI/NOMI paradigm. Since the process of deciding on whether an ECG qualifies for acute reperfusion is a complex one, a tool set will inevitably be necessary for the diagnosis rather than using a single-point measurement of ST-segment. Furthermore, the clinicians should also be aware of the fact that OMI is not solely an ECG diagnosis. In patients with a high clinical suspicion, a careful follow-up and further diagnostic workup should be considered.
All by Emre Aslanger.
Conflicts of interest
| References|| |
Aslanger EK, Meyers HP, Smith SW. Time for a new paradigm shift in myocardial infarction. Anatol J Cardiol 2021;25:156-62.
Aslanger EK, Meyers PH, Smith SW. STEMI: A transitional fossil in MI classification? J Electrocardiol 2021;65:163-9.
Aslanger EK, Meyers HP, Bracey A, Smith SW. The STEMI/NonSTEMI dichotomy needs to be replaced by occlusion MI vs. non-occlusion MI. Int J Cardiol 2021;330:15.
Tziakas D, Chalikias G, Al-Lamee R, Kaski JC. Total coronary occlusion in non ST elevation myocardial infarction: Time to change our practice? Int J Cardiol 2021;329:1-8.
Sankardas MA, Ramakumar V, Farooqui FA. Of occlusions, inclusions, and exclusions: Time to reclassify infarctions? Circulation 2021;144:333-5.
Fibrinolytic Therapy Trialists' (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: Collaborative overview of early mortality and major morbidity results from all randomized trials of more than 1000 patients. Lancet 1994;343:311-22.
Menown IB, Mackenzie G, Adgey AA. Optimizing the initial 12-lead electrocardiographic diagnosis of acute myocardial infarction. Eur Heart J 2000;21:275-83.
Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined-A consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959-69.
Macfarlane PW, Browne D, Devine B, Clark E, Miller E, Seyal J, et al.
Modification of ACC/ESC criteria for acute myocardial infarction. J Electrocardiol 2004;37<(Suppl):98-103.
Wagner GS, Macfarlane P, Wellens H, Josephson M, Gorgels A, Mirvis DM, et al.
AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: Part VI: Acute ischemia/infarction: A scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol 2009;53:1003-11.
Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al.
Fourth universal definition of myocardial infarction. J Am Coll Cardiol 2018;72:2231-64.
Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al.
2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018;39:119-77.
Pride YB, Tung P, Mohanavelu S, Zorkun C, Wiviott SD, Antman EM, et al.
Angiographic and clinical outcomes among patients with acute coronary syndromes presenting with isolated anterior ST-segment depression: A TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) substudy. JACC Cardiovasc Interv 2010;3:806-11.
Martí D, Mestre JL, Salido L, Esteban MJ, Casas E, Pey J, et al.
Incidence, angiographic features and outcomes of patients presenting with subtle ST-elevation myocardial infarction. Am Heart J 2014;168:884-90.
Schmitt C, Lehmann G, Schmieder S, Karch M, Neumann FJ, Schömig A. Diagnosis of acute myocardial infarction in angiographically documented occluded infarct vessel: Limitations of ST-segment elevation in standard and extended ECG leads. Chest 2001;120:1540-6.
Wang TY, Zhang M, Fu Y, Armstrong PW, Newby LK, Gibson CM, et al.
Incidence, distribution, and prognostic impact of occluded culprit arteries among patients with non-ST-elevation acute coronary syndromes undergoing diagnostic angiography. Am Heart J 2009;157:716-23.
Abbas AE, Boura JA, Brewington SD, Dixon SR, O'Neill WW, Grines CL. Acute angiographic analysis of non-ST-segment elevation acute myocardial infarction. Am J Cardiol 2004;94:907-9.
Koyama Y, Hansen PS, Hanratty CG, Nelson GI, Rasmussen HH. Prevalence of coronary occlusion and outcome of an immediate invasive strategy in suspected acute myocardial infarction with and without ST-segment elevation. Am J Cardiol 2002;90:579-84.
Khan AR, Golwala H, Tripathi A, Bin Abdulhak AA, Bavishi C, Riaz H, et al.
Impact of total occlusion of culprit artery in acute non-ST elevation myocardial infarction: A systematic review and meta-analysis. Eur Heart J 2017;38:3082-9.
Aslanger EK, Yıldırımtürk Ö, Şimşek B, Bozbeyoğlu E, Şimşek MA, Yücel Karabay C, et al.
DIagnostic accuracy oF electrocardiogram for acute coronary OCClUsion resuLTing in myocardial infarction (DIFOCCULT Study). Int J Cardiol Heart Vasc 2020;30:100603.
Pendell Meyers H, Bracey A, Lee D, Lichtenheld A, Li WJ, Singer DD, et al.
Accuracy of OMI ECG findings versus STEMI criteria for diagnosis of acute coronary occlusion myocardial infarction. Int J Cardiol Heart Vasc 2021;33:100767.
Hillinger P, Strebel I, Abächerli R, Twerenbold R, Wildi K, Bernhard D, et al.
Prospective validation of current quantitative electrocardiographic criteria for ST-elevation myocardial infarction. Int J Cardiol 2019;292:1-12.
McCabe JM, Armstrong EJ, Ku I, Kulkarni A, Hoffmayer KS, Bhave PD, et al.
Physician accuracy in interpreting potential ST-segment elevation myocardial infarction electrocardiograms. J Am Heart Assoc 2013;2:e000268.
Carley SD, Gamon R, Driscoll PA, Brown G, Wallman P. What's the point of ST elevation? Emerg Med J 2002;19:126-8.
Tandberg D, Kastendieck KD, Meskin S. Observer variation in measured ST-segment elevation. Ann Emerg Med 1999;34:448-52.
Mehta SR, Granger CB, Boden WE, Steg PG, Bassand JP, Faxon DP, et al.
Early versus delayed invasive intervention in acute coronary syndromes. N Engl J Med 2009;360:2165-75.
Kofoed KF, Kelbæk H, Hansen PR, Torp-Pedersen C, Høfsten D, Kløvgaard L, et al.
Early versus standard care invasive examination and treatment of patients with non-ST-segment elevation acute coronary syndrome. Circulation 2018;138:2741-50.
Katritsis DG, Siontis GC, Kastrati A, van't Hof AW, Neumann FJ, Siontis KC, et al.
Optimal timing of coronary angiography and potential intervention in non-ST-elevation acute coronary syndromes. Eur Heart J 2011;32:32-40.
Montalescot G, Cayla G, Collet JP, Elhadad S, Beygui F, Le Breton H, et al.
Immediate vs. delayed intervention for acute coronary syndromes: A randomized clinical trial. JAMA 2009;302:947-54.
Lupu L, Taha L, Banai A, Shmueli H, Borohovitz A, Matetzky S, et al.
Immediate and early percutaneous coronary intervention in very high-risk and high-risk non-ST segment elevation myocardial infarction patients. Clin Cardiol 2022;45:359-69.
Meyers HP, Bracey A, Lee D, Lichtenheld A, Li WJ, Singer DD, et al.
Comparison of the ST-Elevation Myocardial Infarction (STEMI) vs. NSTEMI and Occlusion MI (OMI) vs. NOMI Paradigms of Acute MI. J Emerg Med 2021;60:273-84.
Miranda DF, Lobo AS, Walsh B, Sandoval Y, Smith SW. New insights into the use of the 12-lead electrocardiogram for diagnosing acute myocardial infarction in the emergency department. Can J Cardiol 2018;34:132-45.
Aslanger EK, Meyers HP, Smith SW. Recognizing electrocardiographically subtle occlusion myocardial infarction and differentiating it from mimics: Ten steps to or away from cath lab. Turk Kardiyol Dern Ars 2021;49:488-500.
Aslanger E, Yıldırımtürk Ö, Şimşek B, Sungur A, Türer Cabbar A, Bozbeyoğlu E, et al.
A new electrocardiographic pattern indicating inferior myocardial infarction. J Electrocardiol 2020;61:41-6.
Aslanger E, Yıldırımtürk Ö, Bozbeyoğlu E, Şimşek B, Karabay CY, Türer Cabbar A, et al.
A simplified formula discriminating subtle anterior wall myocardial infarction from normal variant ST-segment elevation. Am J Cardiol 2018;122:1303-9.
Eek C, Grenne B, Brunvand H, Aakhus S, Endresen K, Smiseth OA, et al.
Strain echocardiography predicts acute coronary occlusion in patients with non-ST-segment elevation acute coronary syndrome. Eur J Echocardiogr 2010;11:501-8.
Rowland-Fisher A, Smith S, Laudenbach A, Reardon R. Diagnosis of acute coronary occlusion in patients with non-STEMI by point-of-care echocardiography with speckle tracking. Am J Emerg Med 2016;34:6.e3-6.
Linde JJ, Kelbæk H, Hansen TF, Sigvardsen PE, Torp-Pedersen C, Bech J, et al.
Coronary CT angiography in patients with non-ST-segment elevation acute coronary syndrome. J Am Coll Cardiol 2020;75:453-63.
Emre K Aslanger,
Department of Cardiology, Pendik Training and Research Hospital, Marmara University, Fevzi Cakmak Mah., Muhsin Yazicioglu Cad. No: 10, Pendik 34899, Istanbul
Source of Support: None, Conflict of Interest: None