INTRODUCTION — Chest pain accounts for approximately eight million annual visits to emergency departments (EDs) in the United States . Acute coronary syndrome (ACS) evaluations account for approximately 10 to 20 percent of all these cases. The approaches to chest pain patients in general or those who are likely to have an ACS are discussed separately. (See "Evaluation of the adult with chest pain in the emergency department" and "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)
This group of patients is among the most challenging in acute care medicine in part because of the frequency of the clinical problem. Challenges, which at times compete with one another, include the need to rapidly diagnose ACS so that appropriate interventions can be initiated, the pressure to discharge patients appropriately from busy EDs, and the tendency to overinvestigate chest pain patients, which leads to increased resource utilization.
Two primary goals of the early evaluation of patients with chest pain suggestive of myocardial ischemia are to rapidly confirm the diagnosis of an ACS if possible (a "rule-in") or exclude the diagnosis. Diagnosing ACS in a timely manner is a high priority, as early intervention in patients with ACS has been shown to lead to better outcomes. Conversely, for patients with a low to intermediate risk of an ACS, it is important that unnecessary time and resources not be spent overpursuing the diagnosis.
This topic discusses the evaluation of patients with chest pain who are at low or intermediate risk for ACS as assessed by the results of the initial history (including age and risk factors), physical exam, and electrocardiogram (ECG). The use of troponin testing, risk assessment, and care pathways is presented. A major goal of the topic is to help clinicians identify patients who are candidates for early discharge from the ED.
DEFINITION OF ACUTE CORONARY SYNDROME — The term "ACS" is applied to patients in whom there is evidence of myocardial ischemia or infarction. There are three types of ACS: ST-elevation myocardial infarction (STEMI), non-ST-elevation MI (NSTEMI), and unstable angina (UA). The first two are characterized by a typical rise and/or fall in serum troponin . UA is characterized by new or worsening myocardial ischemia without elevated biomarkers and is often a clinical diagnosis based on history, dynamic ECG changes, or inducible ischemia on stress testing. UA accounts for a smaller proportion of ACS now that there is widespread use of highly sensitive troponin, which can detect very small amounts of myocardial injury. Establishing whether a patient has ACS requires integration of information obtained from a careful patient interview and examination, as well as from serial evaluation of the ECG, troponin levels, and occasionally provocative testing results. (See "Diagnosis of acute myocardial infarction", section on 'Definitions'.)
INITIAL EVALUATION — The primary focus in the very early evaluation (generally within the first 15 minutes after presentation) of patients with possible ACS is to reasonably confirm or exclude in an expeditious manner ACS as the cause for the patient's symptoms (algorithm 1). In this early time period, reasonable confirmation of ACS is generally secured by the finding of diagnostic ECG changes. ACS is reasonably excluded when the probability of ACS is very low (generally considered below a 1 to 2 percent threshold [3,4]). (See 'Risk assessment' below.)
For patients who have or are likely to have an ACS, appropriate management strategies should be initiated (algorithm 2). (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Management'.)
In addition, other life-threatening illnesses should be rapidly identified that would remove the patient from a low- to medium-risk ACS category. (See "Evaluation of the adult with chest pain in the emergency department".)
Prehospital — Patients with symptoms of possible ACS (eg, chest discomfort with or without radiation, shortness of breath, weakness, diaphoresis, nausea, or light headedness) should generally be instructed to call their emergency telephone number, be evaluated by emergency medical services, and be brought to the hospital by ambulance. Emergency medical service evaluation and transport result in more rapid and focused evaluation by streamlining the triage process. Prehospital evaluation should include obtaining a prehospital 12-lead ECG and continuous ECG monitoring.
Immediate in-hospital evaluation — On hospital arrival, patients with symptoms that raise the possibility of myocardial ischemia should have the following performed (see "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department"):
●Continuous ECG monitoring.
●An initial 12-lead ECG within 10 minutes of arrival (even if one has been performed in an ambulance, unless that ECG showed ST-segment elevation) in patients ≥25 years of age with chest pain, or age ≥50 years with chest pain or other symptoms that could represent myocardial ischemia like shortness of breath, altered mental status, upper extremity pain, syncope, or generalized weakness. Very elderly (≥80 years of age) patients with abdominal pain or nausea/vomiting should have an immediate 12-lead ECG as well [2,5].
It is recommended that the ECG be repeated at 20- to 30-minute intervals for any patient with ongoing pain in whom a suspicion of ACS continues. Patients whose ECGs are diagnostic for or strongly suggestive of either STEMI or NSTEMI should be managed for those diagnoses. (See "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes".)
●A brief history and physical examination to screen for signs or symptoms of cardiopulmonary distress. The history should include questions that evaluate whether the chest pain is likely to represent myocardial ischemia. (See "Approach to the patient with suspected angina pectoris".)
As will be discussed below, risk scores also use patient age and coronary artery disease risk factors. (See 'Risk scores' below.)
●At a minimum, the following laboratory tests should be ordered as soon as possible in patients with possible ACS: high sensitivity cardiac troponin (where available), serum electrolytes, serum creatinine, and a complete blood count. (See "Evaluation of the adult with chest pain in the emergency department", section on 'Laboratory studies'.)
While patients who are assessed to be at very low risk of an ACS do not need a troponin test, many institutions have protocols that direct nursing staff to order them based on their assessment, which may be prior to physician evaluation. We believe this is a reasonable strategy.
The results of the first high sensitivity troponin should be available within 60 minutes. (See "Troponin testing: Clinical use", section on 'Diagnosis of acute MI'.)
●A chest radiograph is usually performed in patients suspected of having an ACS, since alternative diagnoses such as heart failure, pneumonia, aortic dissection, pulmonary embolism, or large pericardial effusion may be detected .
Risk assessment — We attempt to assign patients to low, intermediate, or high risk for ACS category, or definite ACS (table 1), based on information obtained from the history, physical examination, ECG, and continuous ECG monitoring (algorithm 1) but before the first troponin level is available. Multiple scoring systems have been evaluated. We prefer the History, ECG, Age, Risk factors, and a single sensitive Troponin (HEART) score, which is used in the HEART Pathway (see 'Care pathways' below). Using this score, individuals with a score of 0 to 3 are considered low risk. There is an element of subjectivity in the HEART score, so internal discussions to improve consistency of use are suggested .
Low-risk patients generally have none of the risk factors found in the table (table 1). Specifically, low-risk patients cannot have a history of coronary artery disease or have ST-segment elevation, significant ST-segment depression, or new T wave inversion.
We manage patients as follows:
●If the patient's likelihood of ACS is very low (<1 to 2 percent) based on the history, physical examination, and initial ECG, additional testing for ACS is not likely to be beneficial.
●All other patients with possible (but not definite) ACS should be further risk stratified by the measurement of serum troponin, if not already ordered. (See "Troponin testing: Clinical use" and 'Troponin testing' below.)
These patients should be monitored with continuous ECG rhythm monitoring at least until return of the first troponin value. Any changes in clinical condition (eg, patient complaints or change in vital signs) should prompt reassessment. Serial ECGs should be performed on patients with continuous pain or changes in symptoms to detect dynamic changes.
●Patients felt to have definite ACS or who are at high risk should be managed accordingly. (See "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Overview of the acute management of ST-elevation myocardial infarction" and "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)
At some lower threshold of pretest probability, the clinician is more likely to cause harm by further testing. It has been suggested that an acceptable lower limit of pretest probability for ACS, above which further testing should be done, is 1 to 2 percent [3,4]. We believe patients below this threshold are very low risk and are unlikely to benefit from additional testing for an ACS. All other patients should receive further testing and risk stratification.
Providers commonly identify very low-risk patients using an experienced clinician's unstructured clinical estimate. In an evaluation of this method, approximately 25 percent of chest pain patients were classified as very low risk (<2 percent risk), and these patients experienced an event rate of 0.7 percent (95% CI 0-2.4) . With the introduction of clinical decision aids, many clinicians and health systems have moved toward more objective classification systems, typically incorporating serum troponin measurements. (See 'Troponin testing' below.)
When formulating the clinician's pretest (before the troponin) probability, it is important to avoid eliminating the possibility of an ACS even when an alternative diagnosis is possible. In patients being evaluated for chest pain, it has been shown that those with a "clear-cut" alternative noncardiac diagnosis still have a 4 percent rate of ACS at 30 days . Similarly, patients with a "clear-cut" alternative noncardiac diagnosis and a Thrombolysis in Myocardial Infarction (TIMI) risk score of 0 had a 2.9 percent rate of ACS at 30 days . As an example, among patients with ACS, a common misdiagnosis is gastroesophageal reflux disease. In two different datasets, it has been shown that patients with ACS commonly describe their pain as burning [11,12]. A gastrointestinal etiology should be assigned only after the diagnosis of a cardiac emergency has been excluded. Further, a trial of antacids or nitroglycerin should not be used as a reliable method to determine whether pain is of gastrointestinal or cardiac origin.
The diagnosis of ACS is more likely to be missed in certain populations. In one study conducted in an American emergency department, patients with ACS who were inappropriately discharged included females <55 years old, Black Americans, those with dyspnea as the primary complaint, and patients with a normal ECG . In addition, older adults often present with atypical histories. We recommend that clinicians incorporate all data elements when forming an unstructured estimate of ACS probability, avoid overreliance on the presence of an alternative diagnosis, and use caution when defining the very low-risk patient population.
While we have identified specific times in this process when evaluation must take place rapidly, evaluation is a continuous process, and new information at any time point can alter a patient's risk category. For example, worsening of symptoms, arrhythmias, or new ECG changes on continuous monitoring can make the possibility of an ACS more likely.
TROPONIN TESTING — In those patients for whom the diagnosis of ACS remains a possibility after rapid evaluation of the history, physical examination, and 12-lead ECG (see 'Risk assessment' above), a high-sensitivity cardiac troponin (hs-cTn) should be obtained as soon as possible. (See "Troponin testing: Clinical use", section on 'Diagnosis of acute MI'.)
Background — Compared with a standard troponin assay, hs-cTn leads to the diagnosis of acute MI in a modest additional number of chest pain patients and may do so earlier in the patients' emergency department (ED) stay . This occurs because hs-cTn detects biochemical evidence of myocardial injury at lower concentrations, and hs-cTn assays allow for discrimination of small changes in concentration even within the normal reference range. However, MI is not ruled in unless there is both a rising and/or falling pattern of values and one value above the upper reference limit (URL)  (see "Diagnosis of acute myocardial infarction", section on 'Definitions'). However, the issue of whether this improves long-term cardiovascular outcomes is debated . In addition, very low hs-cTn values identify patients at low risk of MI in the ED.
With hs-cTn, serial values <99th percentile of the URL make the diagnosis of acute MI quite unlikely, but the value does not exclude the possibility of unstable angina [17,18]. The use of sex-dependent 99th percentile URL is advocated by the Universal Definition of Myocardial Infarction and will be different depending on the assay used. A value of <5 ng/L with the Abbott hs-cTnI assay or with the Roche hs-cTnT assay is capable of identifying patients at extremely low risk of acute MI and whose long-term prognosis is good [19-21].
The negative predictive value of a very low value of a high-sensitivity assay (Abbott cardiac troponin I assay) at presentation to the hospital was evaluated in the High-STEACS prospective cohort (derivation) study of 4870 patients with suspected ACS . With this assay, the limitation of detection was 1.2 ng/L, and a URL (99th percentile) was 34 ng/L in males and 16 ng/L in females. The primary outcome was index MI, or subsequent MI or cardiac death at 30 days. A troponin concentration <5 ng/L had a negative predictive value of 99.6 percent. The effectiveness of combining this test with clinical information for the purpose of selecting patients for early discharge remains to be determined. The one group that had a less robust negative predictive value (NPV) included individuals who presented in two hours or less from the onset of symptoms. Caution is necessary with these early rapid approaches for early presenting patients.
Elevated first troponin — If the first troponin returns clearly elevated in a patient with clinical findings consistent with ACS, the management for NSTEMI likely begins. (See "Overview of the acute management of non-ST-elevation acute coronary syndromes".)
However, this paradigm may be changing with the routine use of increasingly sensitive troponin assays. Data from outside the United States suggest that 11 to 15 percent of patients will be classified as having NSTEMI based on that initial hs-cTn result, of whom 68 to 79 percent will ultimately be adjudicated as having NSTEMI . As these hs-cTn assays are applied to broader patient populations with concomitant medical conditions such as sepsis and renal failure, this positive predictive value is likely to be reduced. This fact needs to be considered by clinicians.
Normal first troponin — If the troponin value is less than the upper reference limit, further evaluation is directed by the clinical presentation and risk factors. (See 'Risk scores' below.)
●For patients whose symptoms remain suspicious for an ACS or who have a low or intermediate risk of ACS (Heart Score ≥1), obtain a second troponin (algorithm 1). For most patients, we obtain a second troponin three hours after the first troponin and use the HEART Pathway approach (see 'Care pathways' below). Monitoring continues until a second troponin returns.
●For selected patients whose symptoms are best explained by a noncardiac diagnosis (eg, costochondritis, pneumonia), and who have a risk for ACS less than 2 percent by clinical evaluation or a Heart Score of zero, the evaluation for ACS can stop .
On occasion, some patients will require a third troponin. Examples include those with stuttering pain, new return of pain while in the ED, patients presenting very soon after the onset of symptoms, and those in whom the clinician has a high degree of concern.
For low-risk patients or those with normal ECGs who present more than three hours after the onset of chest pain [21,24], a value of hs-cTn below the limit of detection of the assay is a sensitive way to rule out acute MI. However, even those who endorse the European Society of Cardiology (ESC) guidelines concur with the need for caution in those who present early after the onset of symptoms [25,26]. The sensitivity of this approach of 99 percent is what ED physicians state that they need . The prognosis during follow-up suggests that the risk of patients who might be discharged using such a strategy is low. In fact, these values are in the range where the frequency of a positive stress test is also low . This strategy, using a single value below the limit of detection, is possible in most regions that use hs-cTn but is not presently validated for application in the United States (for the hs-cTnT assay) because the lowest value that the US Food and Drug Administration (FDA) will permit to be reported in the United States is a higher concentration (6 ng/L) than the limit of detection (3 ng/L for one piece of equipment and 5 ng/L for another). An analysis confirms that the use of a value of 6 ng/L provides slightly less robust information . Other approaches using higher cut-offs are less well validated [19,30,31]. However, with multiple newer assays on the horizon, the likelihood of this becoming a viable option with many assays is substantial. The higher the value used, the greater percentage of the population that can be included with such an approach.
The ESC guidelines advocate for a one-hour rule-out, which includes a three-hour troponin determination for patients indeterminate at one hour, and clinical trials suggest this may work reasonably well [32,33]. However, these approaches have used very small changes in values to make decisions. Those small changes in values have been criticized as being outside of the ability of the assays to measure [32,34]. Data substantiate this concern, suggesting that repeating values will change the designation of a given patient 25 percent of the time . In addition, the validation of the one-hour approach has been criticized for lacking enough patients who present within two hours of the onset of symptoms [25,30]. However, the majority of the data indicate that in most patients, a rule-out diagnosis can be accomplished in two to three hours. This is facilitated by the fact that most patients do not arrive early (within two hours of the onset of symptoms). Thus, any patient who is >3 to 6 hours after the onset of symptoms (assuming no recurrences) and who has a normal cTn value (either hs-cTn or contemporary cTn) can be considered to have ruled out for acute MI . With hs-cTn assays, one- to three-hour rule-outs using assay specific change criteria are usually adequate. There are only rare patients who rule in thereafter .
Borderline or indeterminate first troponin — Uncertainty exists around the optimal management strategy for patients with borderline or indeterminate troponin elevations or changes over time. For those with clear non-MI reasons for elevation, values consistent with prior values, no upward trend, and a history not concerning for unstable angina, attention should be turned to addressing the underlying condition if possible. If the underlying condition is not immediately life threatening, close outpatient follow-up is reasonable. For those not meeting those criteria, management in an observation or inpatient unit for serial troponin measurement and consideration of specialty consultation and/or imaging are prudent. Additional data are needed to define the optimal approach for these patients.
Late presenters — Patients who present 12 hours or more after the onset of symptoms can be diagnostically challenging. If the first hs-cTn is elevated in these patients, clinicians should be careful in their interpretation of changes or deltas between first and second values. Patients with adjudicated NSTEMI with less acute presentations, and those with longer ischemic times, are more likely to present near their peak hs-cTn value. Subsequent values may downtrend or stay about the same, providing false reassurance or misleading the clinician away from the diagnosis of NSTEMI, but still leaving the patient with substantial risk for mortality from ACS . These patients potentially require additional testing. (See 'Noninvasive evaluation' below.)
Risk scores — Risk scores or prediction models have been developed and integrated into care pathways. These tools predict the risk of adverse short-term outcomes (eg, 30-day risk of death, nonfatal MI, or recurrent ischemia). We do not discharge patients at low to moderate risk of an ACS based on the results of the risk prediction models.
The following are summaries of a few of the more widely used risk scores:
●The TIMI risk prediction score (for unstable angina/NSTEMI) has proven predictive ability in patients with suspected or known ACS and has undergone multiple validation investigations [38,39]. The TIMI score (calculator 1) was derived and validated in patients enrolled in clinical trials with ACS, but has since been validated in patients suspected to have ACS . Advantages include simplicity, lack of a need for a nomogram or computer algorithm, and its ability to predict a risk of short-term (30 days) outcome . Among the elements of the TIMI risk score, troponin elevation was the most powerful factor. However, even TIMI 0 patients had a significant 2.1 percent incidence of the composite outcome. As such, the TIMI score has limited utility as a tool to determine who can be discharged as very low risk with no further testing. Once ACS has been documented, then the GRACE risk score performs better than the TIMI score .
●The HEART score (table 1) uses similar components to the TIMI risk score. The HEART score has been widely validated [23,41,42]. However, validation studies have shown the need to add a three-hour troponin to achieve acceptable sensitivity . A score of 0 to 3 identifies a patient at low risk of major adverse cardiovascular events; patients with a score of 4 to 6 have intermediate risk, and those with a score of 7 or greater are high risk. A meta-analysis of 30 studies of the HEART risk score found that a score of 4 or greater had a sensitivity of about 96 percent for the prediction of short-term (39 days or 6 weeks) incidence of major adverse cardiovascular events . The HEART pathway is discussed below. (See 'Care pathways' below.)
●The Calculation Of MI risk probabilities to Manage Patients with SuSpicion of Myocardial Infarction (COMPASS-MI) Project developed a risk assessment tool using data from 23,327 patients with symptoms of MI in 15 European cohorts . Patients with STEMI were excluded. Two assays were studied: hs-cTnT and hs-cTnI, which are the only two presently included in the COMPASS calculator; only hs-cTnT is approved for use in the United States. The algorithm was developed based on samples measured at presentation and once thereafter. A distinction was made between an early second sample (one to two hours) and a later one (>2 hours). The diagnostic and prognostic performance of multiple hs-cTn cutoff combinations were assessed in derivation and validation groups. An interactive risk assessment tool that predicted the risk of MI in the ED and the subsequent 30-day risk of MI or MI/death based on the 15 studies was included in the analysis. In the derivation group, hs-cTnI <6 ng/L and an absolute change of less than 4 ng/L after 45 to 120 minutes resulted in a negative predictive value of 99.5 percent for MI. The associated 30-day risk of MI or death was 0.2 percent. None of the studies included were from the United States, where cTn samples often involve more diverse populations than in many places where the testing is mostly used when the primary issue is evaluation for possible MI. The tool is likely to be helpful for young patients who are being evaluated for possible MI. Prior to recommending wide-spread use of this tool, additional validation is needed, particularly in populations with differing baseline risk.
Most EDs use a care pathway, also called an "accelerated diagnostic pathway," for patients at low to moderate risk of an ACS. These pathways are used to facilitate the discharge of patients with a low risk of a cardiovascular event at 30 days (and who have no other diagnosis requiring further ED evaluation or treatment), using the results from an initial (and sometimes a follow-up) troponin and from an ECG. Some pathways integrate information from a risk prediction score.
It is generally agreed upon by the medical community that protocols designed to facilitate early discharge of patients who are initially suspected to be at low or moderate risk of ACS should have a negative predictive value of greater than 99 percent; that is, 99 percent of individuals chosen for early discharge will not have an adverse cardiovascular event within 30 days.
Patients with objective signs of ischemia (ie, elevated troponin, ST-elevation, ST-depression) or a history of ischemic heart disease (ie, prior MI, history of coronary artery diseases without infarction, prior coronary revascularization) should not be managed using this type of care pathway.
The following pathways have been evaluated and are in clinical use to varying degrees:
●HEART Pathway – The HEART Pathway consists of a modified HEART score (table 1), which is estimated from clinical data, and two troponin values at zero and three hours (algorithm 1) . (See 'Risk assessment' above.)
•If the HEART score is ≤3 points and two troponin measurements are negative (ie, below the 99th percentile), and no new ischemic ECG changes are present, the risk of incident ischemic events is considered sufficiently low for discharge without further observation or diagnostic testing [23,45-48].
•For HEART scores >3 points, the patient is at intermediate or high risk and should be appropriately managed for ACS .
The use of the HEART Pathway approach with sensitive and hs-cTn assays is supported by randomized trials and prospective registry data [7,41,45,47,49]. Examples include:
•Using sensitive troponin assays at zero and three hours, a randomized trial compared the HEART Pathway approach to usual care and found similar rates of death (none in either group) or MI (5 versus 6.4 percent) within 30 days of discharge. Patients in the HEART Pathway group had decreased length of stay (9.9 hours versus 21.9 hours) and lower use of cardiac testing 30 days after discharge (56.7 percent versus 68.8 percent) .
•Using mostly hs-cTn assays, another randomized trial compared the HEART Pathway approach to usual care . This study allowed for discharge if a patient had a HEART score ≤3 points and either one or two negative troponin assays. If a patient was discharged after only one troponin value, a second troponin was obtained the same day or the next day. The combined rate of death, MI, any type of revascularization, any stenosis >50 percent, or unstable angina presentation within 6 weeks of enrollment was lower in the HEART Pathway group compared to the usual care group (18.9 percent versus 22.2 percent). Among patients with a HEART score ≤3 points, death, MI, or revascularization occurred in 1 percent. Time of observation in the ED and readmission rate were similar.
•Using only hs-cTn assays, a prospective registry study conducted in the US found that patients with a HEART score ≤3 points and an initial high-sensitivity troponin value less than the limit of detection (LOD) had a 99 percent NPV and 98.6 percent sensitivity for 30-day incidence of cardiac death or MI (including index visit MI) .
●Single hs-cTn – In early studies, the negative predictive value of an undetectable level of hs-cTn troponin at presentation in a single sample was about 99 percent, somewhat lower than the agreed-upon cut-off [19,21]. When used in conjunction with ECG findings, the NPV is likely greater than 99 percent . In a 2017 meta-analysis of studies that included data regarding patients with a single hs-cTn <5 ng/L, the NPV was 99.5 percent . Given the inability to use a low enough value in the United States, this strategy is not endorsed for use here.
●ESC 0/1-hour pathway – The ESC 0/1-hour pathway rules in or out patients based on measurements separated by one hour and is endorsed by the ESC for use with hs-cTn assays in the context of a validated algorithm. Such validated algorithms are assay specific and require different thresholds for ruling in, ruling out, and observation zones for each assay. In that context, patients deemed low risk based on history, exam, and ECG findings have been safely managed based on zero- and one-hour hs-cTn results. A meta-analysis of this strategy demonstrated a 99 percent sensitivity for MI, and among those ruled out, 30-day event rates were low (death 0.11 percent, MI 0.08 percent) .
Subsequent to the meta-analysis, one of the trials in the meta-analyses reported one-year follow-up of patients randomly assigned to a 0/1-hour pathway or to a 0/3-hour pathway and found no significant difference in the combined rate of all-cause mortality and MI (5 versus 3.8 percent; hazard ratio [HR] 1.32, 95% CI 0.95-1.83) . However, a subgroup analysis of patients with troponin values less than the lower limit of the reference range demonstrated a higher rate of all-cause mortality and MI in the 0/1-hour pathway arm (3.7 versus 2.3 percent; HR 1.60, 95% CI 1.05–2.46).
Similar to the 0/2- and 0/3-hour pathways, the very low troponin value at presentation in a 0/1-hour pathway is not helpful for patients with recent onset (<3 hours) chest pain .
The ESC 0/1-hour pathway has limitations due to reliance on cutoffs below what the FDA allows to be reported, uncertainty about the ideal cutoff and ability to measure those values for some assays, and the performance of this pathway when applied to a more general ED population in whom troponin is frequently ordered.
●ESC 0/2- and 0/3-hour pathways – The ESC 0/2- and 0/3-hour pathways rule out MI in patients without ischemia on the ECG when the cardiac troponin is <99 percent at presentation in patients with symptoms lasting more than three hours . In the ESC 2020 guidelines, 0/1- and 0/2-hour pathways are recommended, with the 0/3-hour pathway as a third option . For those with symptoms lasting less than six hours, a second troponin is performed three hours after the first troponin, and MI is ruled out if the troponin remains <99th percentile or is >99th percentile without a significant change in concentration from the first.
●High-STEACS Pathway – The High-STEACS Pathway measures hs-cTnI at presentation and three hours and incorporates a risk stratification threshold at presentation .
●ADAPT was a prospective, observational study of nearly 2000 patients with chest pain due to suspected ACS that evaluated an accelerated diagnostic protocol . The protocol included pretest probability scoring by the TIMI risk score, ECG, and zero- and two-hour troponin I values. In ADAPT, the accelerated diagnostic protocol successfully identified very low-risk patients; the sensitivity and an NPV were 99.7 percent for the primary end point of major adverse cardiac events within 30 days. In a single-center, randomized validation of the accelerated diagnostic protocol, the proportion of patients safely discharged within six hours of ED arrival increased from 11 to 19 percent with use of the protocol . However, patients identified for early discharge received outpatient stress testing within 72 hours.
●Emergency Department Assessment of Chest Pain Pathway (EDACS-ADP) – The Emergency Department Assessment of Chest Pain Score was incorporated into an accelerated diagnostic pathway and compared with the ADAPT pathway discussed above . Both pathways were effective strategies for chest pain assessment and resulted in an increased rate of early discharges compared with previously reported rates.
●Two 2017 studies compared two or more of these approaches and found that all but the single-hs-cTn approach have an acceptable NPV [26,57-59].
Patients identified as low risk with these approaches can be discharged home with primary care follow-up. However, with all decision aids, it is important to incorporate the provider's clinical gestalt into this decision. The decision to pursue outpatient evaluation, especially if additional testing is likely to be required, should be discussed with the patient. There are many reasonable evaluation strategies, including performing the entire evaluation and stress imaging during the index encounter. We recommend a structured evaluation with the HEART Pathway and expedited discharge of patients stratified as low risk. When pursuing this strategy, we encourage clinicians to discuss this with their patients and consider patient preferences in this decision. (See 'Noninvasive evaluation' below.)
Some patients will have been assessed to be at high risk, despite a normal biomarker, because of the presence of ongoing chest pain, new ECG changes, or heart failure. These patients should be admitted and managed as having unstable angina and/or heart failure. (See "Overview of the acute management of non-ST-elevation acute coronary syndromes".)
In patients classified as not low risk, subsequent noninvasive provocative testing remains an important part of the evaluation. Among patients with normal or nondiagnostic ECG and normal troponin results, up to 10 percent may still have ACS , and 2 to 4 percent may have early adverse events [4,60]. Such patients may be cared for in the ED, in an observation unit, or are admitted.
Observation unit approach — Observation units can be used to complete subsequent assessment with additional troponin values and/or stress chemical cardiac imaging in patients requiring further evaluation. While the use of high sensitivity troponin algorithms has reduced the need for observation units, those without elevated serum troponin but who remain above a 1 to 2 percent probability of ACS will require these additional tests. We recommend observation unit use in such patients who are not low risk according to the HEART Pathway (see 'Care pathways' above). In hospitals without an observation unit, these patients can be placed on the hospital ward in observation or inpatient status.
Observation units can take several forms. At the most basic level, observation is a patient status during which ongoing testing occurs in the ED. The more common scenario is a specialized area, under control of either ED physicians, inpatient physicians, or both, in which patients receive ongoing testing and monitoring in a systematic way.
Chest pain observation units (CPUs) or clinical decision units are a safe and efficient use of resources to evaluate patients with chest pain with both intermediate and low probability of having ACS. In a study of over 1000 mostly low-risk patients, the discharge rate was 82 percent . Since that time, randomized trials have proven their effectiveness and safety [62,63], including one single-center trial of 424 patients at intermediate risk for having ACS, demonstrating that observation units decreased resource utilization without increasing risk . However, a cluster randomized trial of observation unit implementation has questioned the improvement in resource utilization at 14 EDs in the United Kingdom, in which there was no decrease in admission rates . A comparison of inpatient short-stay units with ED observation units was completed among 332 ED patients with chest pain at one center, demonstrating that both are safe and cost effective options . The safety of assigning patients to CPUs has been demonstrated in multiple studies [62,65].
A controversial area in observation unit care is the inclusion of patients with known coronary disease, or those who are unable to exercise. Many studies of chest pain observation units excluded patients with known coronary disease. Similarly, most excluded patients unable to exercise. In principle, however, an observation unit is appropriate for any patient in whom serial negative ECGs, biomarkers, and cardiac imaging will identify a situation where hospital admission will not be necessary. Therefore, we recommend this as an option in centers equipped to conduct this evaluation.
Noninvasive evaluation — Noninvasive evaluation is performed on patients for whom there remains a suspicion of an ACS despite two acceptably low troponin values (algorithm 1). Such patients might be those with a high-risk designation using the HEART Pathway or those in whom the healthcare provider is still concerned based on the patient's risk, as calculated by a risk score such as TIMI (calculator 1). Typically, these patients have a greater than 1 to 2 percent risk of ACS. It should be kept in mind that stress testing is unlikely to be helpful if the pretest probability of coronary artery disease is very low (table 2) . (See 'Risk scores' above.)
We rarely recommend a noninvasive evaluation for patients with a positive troponin due to suspected ACS. These patients should first be evaluated by a cardiology consultant. Patients with a positive troponin who might be candidates for noninvasive testing include those with chronic elevation of troponin.
For those patients in whom a decision is made to perform further testing, the timing and location should be guided by patient and institutional characteristics. Patients for whom there is a concern about the reliability of follow-up should undergo testing prior to discharge. For all patients undergoing further testing, we believe it is reasonable to obtain such testing within 72 hours and usually perform it sooner. Others have suggested that a longer interval is reasonable.
The following is a summary of our approach to noninvasive testing. This topic is discussed in detail separately. (See "Selecting the optimal cardiac stress test" and "Noninvasive testing and imaging for diagnosis in patients at low to intermediate risk for acute coronary syndrome", section on 'Inpatient or outpatient'.)
●Patients with an ECG that is interpretable for ischemic changes can undergo exercise ECG test.
●Patients who are unable to exercise should undergo pharmacologic stress testing combined with imaging (vasodilator stress radionuclide myocardial perfusion imaging [rMPI] or dobutamine stress echocardiography), or computed tomography angiography.
●Patients who have an uninterpretable ECG for ischemia (eg, left bundle branch block, ventricular paced rhythm, left ventricular hypertrophy with strain pattern, or digoxin therapy) should undergo stress testing with imaging (either rMPI or echocardiography).
●Noninvasive rest imaging may be performed in some patients with low-to-intermediate probability of ACS and no prior history of MI who have ongoing or recent chest pain (or equivalent).
•For patients with ongoing chest pain, we recommend injection with radioactive isotope for rMPI or rest two-dimensional echocardiography.
•For patients who present within two hours of symptoms and on whom diagnostic imaging is performed, we suggest rest rMPI. However, a negative study does not exclude unstable angina. In many cases, it should be followed by some form of stress testing.
●Computed tomography angiography, including evaluation of fraction flow reserve, provides another technology to identify patients with low probability of significant coronary disease and/or hemodynamically significant obstructive coronary disease.
Disposition after noninvasive evaluation — After noninvasive evaluation, a final disposition can usually be made (algorithm 1):
●Patients with indeterminate stress testing or imaging results may benefit from cardiology consultation if not already obtained. Many such patients will be admitted.
●Patients with positive stress testing or imaging results should be evaluated by a cardiologist and should generally be admitted to the hospital.
●If the results of stress testing or imaging are negative for a cardiac cause, and other life-threatening components of the differential diagnosis have been ruled out, discharge is appropriate for stable patients. These patients are labeled as having noncardiac chest pain. Many of these patients will carry the diagnosis of nonspecific chest pain while some will ultimately be diagnosed with cardiac causes such as myocarditis/pericarditis, stress cardiomyopathy, or heart failure .
We suggest the following at the time of discharge:
•Provide care for the most likely cause of pain.
•Inform the patient about the basis for the presumptive diagnosis and discuss areas of uncertainty in the diagnosis.
•Establish a plan for follow-up with a care provider, ideally within 72 hours.
•Provide clear and concise written discharge instructions that describe specific reasons for reevaluation and where and when to return.
INDICATIONS FOR CONSULTATION — Indications for cardiology consultation will vary among institutions. The following are reasonable indications for obtaining consultation from a cardiologist:
●Definite evidence of ACS, or when chest pain is accompanied by acute heart failure or hemodynamic instability.
●ECG with difficult-to-interpret ST segments (including paced rhythm or old left bundle branch block) should have a low threshold for consultation.
●Biomarker elevation that may or may not represent ACS (algorithm 1).
●Patients with positive stress testing or imaging results should be evaluated by a cardiologist (and generally admitted to the hospital).
●Imaging reveals ongoing or inducible ischemia, significant coronary artery stenosis, or indeterminate results. Consultation may also be considered for patients with a known history of coronary artery disease, as their tests are more difficult to interpret.
●Complicated cardiac histories, such as multiple prior coronary revascularization procedures.
●Assistance with disposition.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Non-ST-elevation acute coronary syndromes (non-ST-elevation myocardial infarction)".)
SUMMARY AND RECOMMENDATIONS
●Goal of emergency department evaluation – In patients with chest symptoms suspicious for acute coronary syndrome (ACS), the goal of evaluation in the emergency department is to accurately confirm or exclude the presence of myocardial ischemia or other life-threatening conditions. (See 'Introduction' above.)
●Initial Evaluation – The initial evaluation for all patients with chest pain includes the following (see 'Immediate in-hospital evaluation' above):
•Brief and focused history to identify signs and symptoms of life-threatening conditions.
•Electrocardiogram (ECG) within 10 minutes of arrival, and then every 20 minutes for high-risk presentations with ongoing symptoms, or any time symptoms change.
•Sensitive or highly sensitive troponin, basic metabolic panel, complete blood count.
●Patients with objective signs of ischemia or at high risk of acute coronary syndrome – For patients who have or are likely to have an ACS based on either the initial evaluation or subsequent findings (eg, new or changing symptoms, new changes on ECG, new elevation in troponin), appropriate management strategies should be initiated immediately (algorithm 2), and further noninvasive evaluation for ischemia is not necessary. (See 'Initial evaluation' above and "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Management'.)
●Normal first troponin – If the troponin value is less than the upper reference limit, further evaluation is directed by the clinical presentation and risk factors. (See 'Normal first troponin' above and 'Late presenters' above and 'Risk scores' above.)
•For most patients whose symptoms are best explained by a noncardiac diagnosis (eg, costochondritis, pneumonia), and who have a risk for ACS less than 2 by clinical evaluation or a Heart Score of zero, the evaluation for ACS can stop (algorithm 1).
•For patients whose symptoms remain suspicious for an ACS or who have a low or intermediate risk of ACS (HEART Score ≥1), obtain a second troponin (algorithm 1). For most patients, we obtain a second troponin three hours after the first troponin and use the HEART Pathway approach. (See 'Troponin testing' above and 'Care pathways' above.)
●Normal second troponin – If the second troponin value is also normal, we use the HEART score to reestimate risk (table 1) and the HEART Pathway (algorithm 1) to determine the next step in management (see 'Care pathways' above):
•For HEART Pathway score values ≤3 and two negative troponin measurements three hours apart, the patient can be discharged with follow-up in the next week.
•For HEART Pathway score values >3 and two negative troponin measurements three hours apart, the patient should remain under observation and undergo non-invasive ischemia evaluation prior to discharge.
●Noninvasive evaluation – For those patients in whom a decision is made to perform further testing, the timing and location should be guided by patient and institutional characteristics. (See 'Noninvasive evaluation' above.)
•For most patients deemed low to intermediate risk of ACS, we obtain stress testing or imaging prior to discharge.
•The choice of cardiac imaging or stress testing and the type of test is determined by patient characteristics and test availability.
●Disposition after noninvasive evaluation - After completion of an appropriate noninvasive diagnostic test (eg, stress test, cardiac imaging), determine the patient's final disposition. (See 'Disposition after noninvasive evaluation' above.)
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