Imaging in patients with acute chest pain in the emergency department

Scope of the problem

Chest pain is one of the most common chief complaints in subjects presenting to the emergency department (ED), representing 5% of all ED visits. ^, In the United States, approximately seven to eight million individuals present to the ED each year for evaluation of chest pain, at an annual cost of approximately five billion U.S. dollars for the care they are provided. Despite this high frequency, only 10% to 20% of these visits are truly the result of an underlying cardiovascular cause and, among those, only 5% are caused by a life-threatening acute coronary syndrome (ACS).

Therefore the majority of patients who present to the ED with chest pain are at low risk for developing adverse cardiac events in the short term and may therefore be safely discharged from the ED without the need for hospital admission once they are identified as being at very low risk. Identifying such patients quickly, however, has been a challenge, and the pursuit to accurately quantify risk among ED patients with chest pain has been an area of robust investigation for decades.

Because the goal of evaluation in the ED is to triage patients in a rapid and safe manner, various clinical prediction models were developed to risk-stratify such patients, aid in cutting costs, and reduce overcrowding in the ED. These models were often based on specific patient-related clinical features and objective data collected in the ED and were an initial attempt to quantify the likelihood of ACS to aid in triage decisions, rather than have clinicians rely on their own intuition and experience. Although the models stratified patients more accurately than clinicians, their performance was not sufficient to engender adoption because they were likely to miss cases of ACS events. Although the risk of missing ACS among ED patients is overall low and reportedly in the range of 1% to 2%, failure to accurately recognize these patients is not without consequences and is at the expense of up to a twofold increase in the risk for mortality compared with patients who are admitted and evaluated in the hospital. ^{, ,} Further more, although this 1% or so epidemiologic risk has been considered acceptable among experts, individual cases of missed diagnoses have led to important legal concerns and malpractice litigation among ED clinicians. These safety issues have understandably resulted in the adoption of a very conservative approach to triage in such patients, including a common practice of holding patients for observation, ordering costly diagnostic tests, and maintaining a very low threshold for hospital admission.

The lack of sufficient and rapid stratification encouraged clinicians and investigators to develop strategies to further improve the risk stratification process and reduce the risk for missed ACS events. Of particular interest and focus has been the goal of rapidly identifying very low-risk patients (commonly quantified as being at <1% risk of ACS or myocardial infarction [MI] over the subsequent 30 days from presentation), with the implication that such patients could be safely discharged directly from the ED. Over the past 20 years, substantial evidence from randomized strategy trials has evolved.

Evaluation of patients with chest pain in the emergency department

The aim of evaluating patients with chest pain in the ED is to identify ACS early on and rapidly impose an aggressive therapeutic plan. History-taking and a 12-lead electrocardiogram (ECG) remain the most important initial diagnostic tools that are typically readily available for all subjects coming to an ED with chest pain. Because initial ECG changes detect less than two-thirds of patients with ACS, ECGs are often serially tested at 20 to 30 minute intervals for patients with persistent symptoms. ^, In clinical practice, however, only a minority of patients have typical anginal symptoms with a clearly interpretable ECG demonstrating new or dynamic changes (clear-cut ST-segment elevation or depression) consistent with ischemia. The majority of patients either present with atypical symptoms or have ECGs that are difficult to interpret because of either baseline changes, findings of unknown chronicity, or complete absence of ECG features of ischemia. Thus, any approach relying on history and ECG will, by its nature, be limited and insensitive. The main importance of the initial ECG is to quickly capture the 10% to 15% of presenting subjects who will have obvious ST-segment changes of elevation or depression to rapidly move them into an ACS treatment pathway.

The development of cardiac troponin assays, and more recently high-sensitivity troponin assays, has changed the standard by which patients with chest pain are evaluated in the ED. Troponin has now become the fundamental cornerstone in the diagnosis of MI and has been integrated into the iterations of the universal definition of MI, including the most recent iteration. Although prior non–cardiac-specific enzymes, namely aspartate transaminase, lactate dehydrogenase, creatine kinase, and myoglobin, were available before troponin, they were not diagnostically helpful for triage decisions in the ED because they lacked specificity to cardiac myocytes and their detection times in patient sera after the onset of an ACS event were markedly delayed.

Serial assays of high-sensitivity troponin at presentation and 1 hour later have been associated with high negative predictive value of 99% to rule out MI, whereby the absolute change of the level within 1 hour may be used as a surrogate for absolute change over 3 to 6 hours (specific cutoff levels are assay-specific). Thus the European Society of Cardiology (ESC) guidelines have adopted the 0/1-hour algorithm to rapidly diagnose and safely and effectively triage patients with suspected ACS/ non-ST-elevation myocardial infarction (NSTEMI). When further validated among 4368 patients presenting to the ED, the 0/1-hour algorithm proved to be safe for triaging patients, particularly for ruling out NSTEMI among those with negative serial assays or ruling in NSTEMI among those with elevated initial assay or a significant change in troponin concentration over 1 hour. Therefore, based on the available risk stratification models, it seems the combination of patient clinical features, ECG, and serial troponin is necessary for adequate risk stratification, with a negative predictive value effectively approaching 100%. These important studies focus on one end of the spectrum of patients, those with negative high-sensitivity troponin values within a relatively short time frame from ED presentation, and identify a group of patients for whom safe direct discharge from the ED is reasonable.

Despite several advantages over earlier generation assays, the high-sensitivity nature of contemporary troponin assays also brings with it a new set of limitations. In patients presenting with new-onset chest pain, high-sensitivity troponin has been demonstrated to be elevated in many non-ACS cardiac conditions, including arrhythmias, acute decompensated heart failure, myocarditis, and noncardiac conditions such as sepsis and liver disease.

Perhaps, most importantly, real-world registries have demonstrated that approximately 30% of patients have “border zone” values of high-sensitivity troponin that do not fall in either category to conclusively rule in or rule out acute cardiac ischemia. Between the two extremes of risk lies an intermediate group that does not fulfill the criteria for either. For example, in one large registry among patients with a “rule-out” range of high-sensitivity troponin I or T, the prevalence of NSTEMI was 0.3% and 0.2%, respectively, well below the 1% risk threshold to potentially enable direct discharge. Among those with “rule-in” ranges, prevalence of ASC/NSTEMI was very high. Nevertheless, among those patients with borderline values of high-sensitivity troponin I or T in the 0/1-hour testing algorithm, NSTEMI was ultimately diagnosed in 7.2% and 14.2%, respectively. Thus, even though 80% to 90% of such patients will not ultimately rule in for an ACS, these patients have an intermediate likelihood of ACS at that early time of presentation and need further evaluation.

In clinical practice, these patients comprise a diagnostic challenge to clinicians because the appropriateness for admission and further testing remains unclear and the safety of discharging directly from the ED is also not practical because most clinicians will not be comfortable with the fact that an ACS has been adequately ruled out. Accordingly, additional risk stratification in this intermediate risk group is an unmet need. With the application of cardiac imaging modalities in this setting, the utility of these diagnostic tests as a means of risk stratification may address the uncertainty surrounding these intermediate-risk patients who present to the ED with symptoms suggestive of ischemia but with nondiagnostic ECG findings and high-sensitivity troponin findings that do not conclusively place the patient at either extreme of the risk spectrum ( Fig. 11.1 ). In contemporary practice, with the increasing deployment of high-sensitivity troponin assays, it is this intermediate or border zone group of patients who are most likely to benefit from the information provided by imaging.

The ischemic cascade and the rationale for use of noninvasive imaging

The rationale to use noninvasive imaging to interrogate various underlying pathophysiologic factors in the evaluation of chest pain in the ED is based on the sequence of events that occur in the ischemic cascade . During an ischemic event, a series of occurrences ensue in a hierarchical and sequential manner. Early on, the initial mismatch between myocardial oxygen supply and demand during an ischemic event is associated with potentially detectable regional coronary flow heterogeneity between subendocardial and subepicardial perfusion and/or between one myocardial region and others. This mismatch leads to the development of perfusion defects that are detectable on imaging. Interestingly, these defects may persist for several hours after the inciting event, even after the resolution of clinical symptoms. With worsening of the supply/demand mismatch, metabolic changes begin to occur that initially cause diastolic functional abnormalities and subsequently systolic dysfunction manifested by regional systolic wall motion abnormalities. Finally, electrical abnormalities, manifested as ischemic findings on ECG, and then clinical manifestations, such as chest pain, are the later events in the ischemic cascade to develop. ^,

Therefore patients who present to the ED with ongoing chest pain due to myocardial ischemia are likely to already have perfusion defects and wall motion abnormalities on arrival, potentially detectable by noninvasive imaging. The usefulness of imaging to rule out an ACS is based on the sensitivity of the test (in turn based on its spatial and temporal resolution to pick up subtle changes) as well as the timing of imaging. Many patients are not continuously symptomatic during an ED evaluation, and the resolution of symptoms may be associated with a resolution of the abnormality to be detected by imaging. This appears to be particularly important for detecting wall motion abnormalities because they resolve more quickly than perfusion abnormalities.

Therefore the use of noninvasive imaging in the ED setting among patients with symptoms suggestive of ischemia confers a significant advantage in the detection of ACS and may be a useful tool for diagnosing and triaging these patients and in the decision-making process.