The Need for Uniform Definitions in the Regionalized Care of ST‐segment Elevation Myocardial Infarction

Abstract

Treatment modalities for ST segment elevation myocardial infarction (STEMI) have rapidly evolved over the past several years. However, minimizing total coronary ischemia time, defined by symptom onset to reperfusion therapy, has been the cornerstone of treatment.1 There are currently two types of hospitals that provide reperfusion therapy: those with the ability to provide primary percutaneous coronary intervention (PCI) and those without PCI capability that provide fibrinolytic therapy. Decreasing reperfusion times has been shown to improve morbidity and mortality after STEMI.2 Thus, identifying which process-of-care strategies improve time to reperfusion is paramount.3 Launched by the American College of Cardiology (ACC), the “Door to Balloon (D2B): An Alliance for Quality” is a campaign to improve the timeliness of PCI. The ACC goal is to achieve reperfusion within 90 minutes for 75% of patients. Toward that end, various emergency medical services (EMS) systems have begun to regionalize cardiac care by identifying and transporting patients identified with a STEMI in the out-of-hospital setting directly to hospitals capable of providing PCI.4 In evaluating STEMI process-of-care strategies, there exist problems with consistency in nomenclature and uniformity of definitions. Research involving STEMI management depends on the accurate reporting of clinical events, time intervals and time points, and pathophysiologic changes, yet basic terms and parameters for time measures are vague and ill-defined. Clinical investigators from many different specialties, such as emergency medicine, cardiology, and out-of-hospital care, contribute to the multidisciplinary knowledge base of the management of myocardial ischemia. Examples of terms utilized with variable meaning include the following: “false-positive cardiac catheterization laboratory (CCL) activation,”“STEMI,”“culprit lesion,”“door-to-balloon time,”“medical contact-to-balloon time,” etc. Although diversity in disciplinary backgrounds often promotes research, it can be detrimental if it contributes to the lack of a common language and communication between investigators. Thus, similar to how investigators in resuscitation developed the uniform, “Utstein style,” it will be important to establish consistency in nomenclature and guidelines for reporting coronary revascularization data. A uniform vocabulary of terminology and definitions will help improve the clarity of scientific communication and the comparability of investigations. Changing an entire region’s EMS system to direct STEMI patients to centers providing PCI requires enormous financial and personnel commitment, yet whether or not regionalizing cardiac care is cost-effective can only be determined through systematic comparisons using sound research methodology, which requires standard terminology. The concept of false-positive activation of the CCL warrants discussion. To meet the D2B goal of reperfusion within 90 minutes, PCI-capable hospitals mobilize the 24/7 on-call CCL team as soon as a patient is identified as having a STEMI, whether it is in the out-of-hospital or hospital setting. Maintaining 24/7 response of the CCL team is dependent on willing staff cardiologists and nurses, potential fixed costs for on-call pay, and addition costs incurred for each activation. To minimize expenses, investigators are evaluating process-of-care strategies to minimize “false-positives.” At this time, however, multiple definitions for what constitutes a false-positive CCL activation exist in the literature, and these differing definitions of false-positive CCL activations make it difficult, if not impossible, to compare studies. Depending on the definition used, the false-positive CCL activation rate ranges from 0%5 to 26% (unpublished data). For example, Larson et al.6 defined false-positive in their study as one in which there was any of the following: no culprit artery (14%), no significant coronary artery disease at catheterization (9.5%), or negative cardiac biomarkers (11.2%). With the use of this definition, a patient who has no culprit lesion identified during CCL, with positive biomarkers and an electrocardiogram (ECG) universally interpreted by the field, emergency department (ED), and cardiology services as a STEMI, is included as one of the false-positives. Reporting a 0% (0/51) false-positive rate, Kraft et al.5 defined false-positive as a lack of an occluded vessel on catheterization, without commenting on biomarkers, or concordance or discordance of ECG interpretations among field providers, ED physicians, and cardiologists. In contrast, Khot et al.7 reported a 1% (1/97) false-positive rate for catheterization lab activation, which was defined as when catheterization was deemed unnecessary by a cardiologist (one example involved the patient who had flash pulmonary edema, presumptively explaining his ECG interpretation) or when the ED ECG interpretation differed from the cardiologist’s interpretation. Khot et al. also did not consider biomarkers as one of the criteria, nor did he consider it a false-positive if a patient with a normal coronary angiogram had an ECG interpreted by both cardiologist and ED physician as a STEMI. In van de Loo et al.,8 although false-positive was actually not explicitly defined, they report a 5% false-positive rate (4/74). Similarly, Bradley et al.3 vaguely stated that when the catheterization team was activated but was “not needed,” a “false alarm” occurred. The underlying confusion about what constitutes a false-positive is due to the ambiguity in the definition of a STEMI. If the ST segments evolve over time and pathologic Q waves develop, one is more confident about identifying the infarct-related artery and the diagnosis of STEMI. Nondynamic or nonevolving ST elevation may be due to a left ventricular aneurysm or other fixed pathology and is less likely to be due to an acute myocardial infarction. According to the ACC, the European Society of Cardiology (ESC), the American Heart Association (AHA), and the World Heart Foundation (WHF) 2007 global task force, STEMI (in the absence of left ventricular hypertrophy and left bundle branch block) ECG criteria, in the presence of symptoms, include the following: “new ST elevation at the J-point in two contiguous leads with the cut-off points: >0.2 mV in men or >to 0.15 mV in women in leads V2-V3 and/or >to 0.1 mV in other leads”; or, indicative of posterior myocardial infarction, “new horizontal ST depression >0.05 mV in V1-V3 with prominent R wave or R/S ratio >1.”9 Despite this explicit definition of STEMI put forth by the ESC/ACC/AHA/WHF global task force, none of the studies evaluating regionalization of cardiac care referred to it. The role of biomarkers in the definition of STEMI should also be discussed. According to the ESC/ACC/AHA/WHF task force, to establish the diagnosis of myocardial infarction, an elevated biomarker level above the threshold level is required. Although an elevation of biomarkers, such as troponin I, reflects myocardial necrosis, there are multiple causes of troponin elevations in the absence of overt ischemic heart disease. For example, myocardial necrosis may result from myocarditis, aortic dissection, pulmonary embolism, congestive heart failure, renal failure, cardiac contusion, drug toxicity, etc. Thus, demonstration of a rising or falling pattern may be necessary to distinguish background elevated troponin levels in patients with chronic renal failure or dilated cardiomyopathy.10 Because cardiac biomarkers are generally considered a more sensitive marker of ischemia and infarction than the ECG, it would be difficult to argue that a patient had a STEMI in the absence of positive biomarkers, unless the myocardial infarction occurred during CCL and immediate reperfusion followed. Note that the prevalence of a normal coronary angiogram in a patient with chest pain and ST elevation seen on ECG with positive cardiac biomarkers is thought to be extremely rare—0.7% (7/1,004 patients).11 If “ST elevation” is an electrocardiographic definition, angiographic criteria should not be considered as part of the definition of STEMI. From the perspective of the emergency physician, the critical decision point is to identify whether or not a patient needs to undergo a cardiac catheterization with the potential for PCI. The interventional cardiologist validates this decision by performing catheterization, even if no treatable lesion is later present. Similarly, the out-of-hospital care provider, who aims to improve the accuracy of CCL activation before ED arrival, also relies on electrocardiographic criteria for a STEMI. In fact, in many EMS systems that have moved toward regionalization of STEMI care, the out-of-hospital ECG dictates whether or not the patient will be transported to a hospital with PCI capability. Certainly, from the out-of-hospital perspective, if the ED ECG confirms the field ECG, the patient was appropriately managed and triaged. In contrast, interventional cardiologists may state that the results of the angiogram are critically important in defining a true positive STEMI. If catheterization criteria are considered, it is difficult to know how to classify the patient who ultimately does not undergo catheterization despite meeting the electrocardiographic criteria, because of prohibitive comorbidities (septic shock) or personal preference. If only electrocardiographic criteria are used, such a patient would have been classified as a true-positive STEMI. However, if angiographic criteria are considered, this patient would have been excluded. A similar classification dilemma arises in the patient who meets ECG criteria for ST elevation but has no demonstrable lesion (apical ballooning syndrome, aneurysm, etc.). From the perspective of the ED, even if a patient’s cardiac catheterization ultimately demonstrates clean coronaries, no reasonable emergency physician would argue that the patient wrongly underwent diagnostic cardiac catheterization if the patient had presented with a chest pain history consistent with myocardial ischemia and ST elevation meeting ECG criteria for STEMI. The concept of culprit lesion is also ill-defined. If the interventional cardiologist finds and stents a 70% occlusion in the right coronary artery in a patient whose ECG demonstrates ST elevations in leads V1–V3, was this a true-positive CCL activation? Knowledge of pathophysiology would lead us to conclude that there should be concordance between the pathologic lesion and the ECG distribution of ST elevations, yet if appropriate CCL activation is defined as any performance of PCI, then this patient would have been misclassified as a true-positive CCL activation. The term, culprit lesion should therefore be standardized, such that it is defined by a certain percentage of luminal narrowing in an artery, concordant with the associated electrocardiographic ST elevation abnormality. Other terms warrant standardization. What is the definition of D2B time? When is the “door” time? Is it when the patient enters the ED? When the patient gets registered? When the patient has his first ED ECG with a reliable computerized time? When is “balloon” time? Is it when the wire crossed the lesion in the coronary artery? Or when the actual balloon has crosses the lesion? Or is it when TIMI grade flow has been established? Similar confusion confounds the concept of door-to-needle (D2N) time. There are other time intervals, such as medical contact-to-balloon times that are being discussed, and these terms also need more explicit parameters. Is “medical contact” when the patient makes contact with the 9-1-1 operator? When the paramedic arrives on scene with the patient? When the field ECG is performed? The American Heritage Dictionary defines an “interval” as the “temporal duration between two specified events.”12 Thus, there should be a beginning and end point, such that one specified time point anchors the start of the interval while another specified time anchors the end of the interval. The significance of time intervals in the management of STEMI is exemplified by the emphasis on achieving a D2B time of <90 minutes, as well as achieving the shortest possible D2N time, medical contact-to-balloon time, etc. However, without explicitly defining the anchor points of each of these time intervals, it is difficult to compare the various studies and understand which strategies are effective in decreasing total myocardial ischemia time. In summary, standardization of the terminology for the management of STEMI is needed to improve the understanding and reporting of research. It is time for a multidisciplinary panel of experts from emergency medicine, cardiology, and EMS to convene a consensus conference to establish uniform definitions and reporting criteria in the management of STEMI.