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1evaluation of Chest Pain and Acute Coronary Syndromes PDF
1evaluation of Chest Pain and Acute Coronary Syndromes PDF
KEYWORDS
Chest pain Acute coronary syndrome Troponin Coronary CT angiography
KEY POINTS
Chest pain is a common complaint in the emergency department, but less than 15% of patients are
diagnosed with acute coronary syndrome.
Risk stratification tools incorporating cardiac troponins have created new accelerated diagnostic
pathways that are highly accurate and sensitive.
Coronary computed tomography angiography can be used in low-risk to intermediate-risk patients
for diagnostic testing with high accuracy.
Disclosure: Dr A.M. Chang has research grants from Janssen. She has done consulting work for Siemens. Dr D.L.
Fischman has stock ownership in Medtronic Corporation and Boston Scientific Corporation (which has no
bearing on the material covered in this article). Dr J.E. Hollander has research grants from Alere, Siemens,
Trinity Biotech, and Roche. He has also done consulting work for Janssen.
cardiology.theclinics.com
a
Department of Emergency Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Thomas
Jefferson University Hospital, 1020 Sansom Street, Suite 241, Thompson Building, Philadelphia, PA 19107, USA;
b
Cardiac Catheterization Laboratory, Sidney Kimmel Medical College, Thomas Jefferson University, Thomas
Jefferson University Hospital, 925 Chestnut Street, Philadelphia, PA 19107, USA; c Finance and Healthcare En-
terprises, Department of Emergency Medicine, Sidney Kimmel Medical College, Thomas Jefferson University,
Thomas Jefferson University Hospital, 1025 Walnut Street, Suite 300, Philadelphia, PA 19107, USA
* Corresponding author.
E-mail address: Anna.m.chang@jefferson.edu
published in 2012,5 which defined this as myocar- conducted a systematic review of the accuracy
dial cell death caused by prolonged ischemia. MI of the history, physical examination, ECG, and
is determined by clinical features including electro- risk factors. Similarly, symptoms were not useful
cardiogram (ECG) and biomarker findings. There in isolation for risk stratification. In both studies, ra-
are 5 classifications of acute MI (Table 1), and clini- diation to right arm or both arms was more specific
cians should be aware of these. Usually, clinicians than radiation to left arm (specificity, 96%; likeli-
are focused on type I MI, but supply-demand hood ratio (LR), 2.6 [95% confidence interval (CI),
mismatch or infarction in the absence of thrombotic 1.8–3.7] vs specificity 69%; LR, 1.3 [95% CI, 1.2–
occlusion (type 2) is also common. 1.4]). Other helpful historical factors included
similar to prior ischemia or MI (specificity, 79%;
LR, 2.2 [95% CI, 2.0–2.6]) and associated diapho-
RISK STRATIFICATION IN THE EMERGENCY
resis. There were mixed responses associated
DEPARTMENT
with nausea and vomiting. Response to nitroglyc-
History
erin was also unhelpful, whereas descriptions of
Recent systematic reviews of investigations indi- the pain, such as pleuritic, positional, or sharp,
cate that history and physical examination are were only minimally helpful in decreasing the likeli-
not helpful in symptomatic patients with acute hood of ACS. In addition, these features, which are
chest symptoms. Swap and Nagurney6 conducted usually associated with lower probability of ACS,
a systematic review of chest pain characteristics have only poor to fair interrater reliability.8
from observational studies and found that certain In recent years, pain scores have received a lot
characteristics increased or decreased the likeli- of attention; however, Edwards and colleagues9
hood of ACS or AMI, but none are useful to dispo- found that there was no difference in AMI or 30-
sition the patient. Fanaroff and colleagues7 day outcomes in patients with pain rated as severe
(9 or 10 on 10-point scale) or not.
Table 1
Classification of acute myocardial infarction Cardiac Risk Factors
types Traditional cardiac risk factors such as hyperten-
sion, diabetes, hyperlipidemia, and tobacco use
Type 1 Spontaneous MI related to ischemia
caused by a primary coronary are often used to predict the long-term risk of cor-
event such as plaque erosion and/ onary artery disease (CAD) and are included in
or rupture, fissuring, or dissection models such as the Framingham Risk Score.10
Type 2 MI secondary to ischemia caused by However, these are not useful for predicting ACS
either increased oxygen demand in symptomatic patients in the ED. Recent studies
or decreased supply such as caused have found that up to 12% of patients with AMI
by coronary artery spasm, had no cardiac risk factors.11,12
coronary embolism, anemia,
arrhythmias, hypertension, or Prior Cardiac History
hypotension
Type 3 Sudden unexpected cardiac death,
Patients with a prior normal stress test are at the
including cardiac arrest, often same risk of 30-day adverse cardiovascular events
with symptoms suggestive of as patients who have not previously undergone
myocardial ischemia, stress testing.13,14 Stress testing does not assess
accompanied by new ST elevation, whether nonobstructive plaque existing at the
or new left bundle branch block, time of the test will subsequently rupture leading
or evidence of fresh thrombus in a to ischemia. Thus, knowledge of a recent normal
coronary artery by angiography stress test may not help inform current ACS risk;
and/or at autopsy, but death patients with a prior normal stress test still had a
occurring before blood samples
5% event rate at 30 days. In contrast, prior invasive
could be obtained, or at a time
coronary angiography results are useful for risk
before the appearance of cardiac
biomarkers in the blood stratification of patients. Patients with no or minimal
(<25%) stenosis have an excellent long-term prog-
Type 4a MI associated with percutaneous
coronary intervention nosis, with 90% free from 1-vessel disease and
greater than 98% free from MI nearly a decade
Type 4b MI associated with stent thrombosis
by angiography or autopsy
later.15,16 Thus, recent coronary angiography with
normal or minimally diseased vessels makes the
Type 5 MI associated with coronary artery
development of an ACS extremely unlikely and
bypass grafting
may be helpful during the current visit.
Chest Pain and Acute Coronary Syndromes 3
Given the ability of new highly sensitive troponin provocative testing, specifically stress imaging
assays to detect smaller amounts of cardiomyo- during admission or shortly after discharge. In addi-
cyte damage within a shorter time of onset, tion, although these strategies may effectively help
many new biomarker strategies have been evalu- rule out or rule in AMI in a significant proportion of
ated for the rapid rule-out of AMI. In 2015 the Eu- patients, the European Society of Cardiology
ropean Society of Cardiology recommended (ESC) also incorporates an observe middle ground,
troponin testing at 0 and 3 hours, or at 0 and 1 in which troponin level increases do not meet
hour with the use of validated algorithms for the criteria to rule in and no alternative explanation for
select group of patients.26 As with any algorithms the increase is identified.26 Clinicians need to use
for patient care, there are some caveats: these judgment in determining the best further test.
should only be used in conjunction with all avail-
able clinical information; if a patient presents early
Risk Stratification Scores
in chest pain, the second cTn level should be ob-
tained at 3 hours, because of the time dependency Clinical prediction rules and decision aids have
of troponin release; and because late increases in helped clinicians incorporate clinical and
cTn level have been described, serial cTn testing biomarker findings to risk stratify patients. These
should be pursued if the clinical suspicion remains rules and aids are helpful in estimating pretest
high or whenever the patient develops recurrent probability, and may help facilitate patient safety.
chest pain. Table 2 provides a summary of these Common risk assessment rules used in the ED
pathways for troponin testing times. include the Thrombolysis in Myocardial Infarction
In the 3-hour protocol, AMI is ruled out if concen- (TIMI) risk score,31,32 and more recently, the
trations of high-sensitivity cTn (hs-cTn) remain in the HEART (History, ECG, Age, Risk factors and
normal range at presentation and at 3 hours later, Troponin) score.33 Other scores include the
and if the patients remained pain free and continue Platelet Glycoprotein IIb/IIIa in Unstable Angina:
to be at low risk of in-hospital mortality as quantified Receptor Suppression Using Integrilin Therapy
by a Global Registry of Acute Coronary Events (PURSUIT) risk score,34 the GRACE risk score,35
(GRACE) score less than 140.26 In patients present- Vancouver rule,36,37 and North American Chest
ing more than 6 hours after chest pain onset (which Pain Rule.38 Table 3 shows the risk scores and
can be reliably quantified), a single blood draw at early discharge criteria based on these scores.
presentation is considered sufficient. Patients are The TIMI score was derived from a group of pa-
considered ruled in if they have a clearly increased tients with non–ST-elevation myocardial infarction
hs-cTn blood concentration at presentation or if but has been validated for use in the ED setting.
the 3-hour sample shows an assay-specific relevant The TIMI risk score is a 7-item score that, when com-
change. A similar approach using hs-cTn achieves a bined into a score of 0 to 7, allows emergency phy-
high negative predictive value and sensitivity by also sicians to risk stratify patients whether or not they
taking into account absolute concentration changes have ACS. When applied to a broad-based popula-
within 2 hours, and allows clinicians to safely rule tion of patients with chest pain, it performed similarly
out AMI even in patients with mild nonspecific and was able to risk stratify the patients with respect
ECG abnormalities. This strategy allows the rapid to 30-day death, AMI, and revascularization.32 The
rule-out of AMI in up to 60% of patients.27–29 More- ASPECT (ASIA PACIFIC EVALUATION OF CHEST
over, this strategy also includes a rule-in algorithm PAIN TRIAL) and ADAPT (A 2hr Accelerated Diag-
that provides a positive predictive value of 70% to nostic Protocol to Assess patients with chest Pain
80% for AMI. symptoms using contemporary Troponins as the
The 1-hour algorithm is identical to that of the only biomarker) studies combined the use of a modi-
0-hour and 2-hour algorithm and is based on infor- fied TIMI risk score with 0-hour and 2-hour troponin
mation provided by hs-cTn blood concentrations. measurements.27,39 Between 10% and 20% of pa-
This approach may allow for safe rule-out of AMI tients were considered low risk if a TIMI score of
even in patients with mild nonspecific ECG abnor- 0 was used, and up to 40% for TIMI less than or
malities. This strategy is very effective and allows equal to 1. The negative predictive value was
an accurate disposition for about 75% of patients: 99.7%. This study is widely implemented in Queens-
60% rule-out and 15% rule-in of AMI. Another land, Australia, but has not been replicated in the
quarter of the patients are ultimately ruled in.30 United States.
Importantly, these rapid pathways have not been The HEART score relies on a 10-point scale
used in the United States in a clinical setting, but will based on the patient’s history (H), ECG results
soon be available in clinical practice. It is also crit- (E), age (A), risk factors (R), and troponin test result
ical to note that, once these patients have been (T), and a score less than or equal to 3 is consid-
ruled out, the guidelines still recommend ered a low-risk cohort.40 Backus and colleagues33
Table 2
Accelerated diagnostic pathways
Eligible population size is quantified by the percentage of consecutive patients with chest pain eligible for this early triage strategy: 1, z20%; 11, z40%; 111, z50% to 75%.
Abbreviations: ADP, accelerated diagnostic protocol; ESC, European Society of Cardiology; GRACE, Global Registry of Acute Coronary Events; hs-cTnI, high-sensitivity cardiac
troponin I; hs-cTnT, high-sensitivity cardiac troponin T; TIMI, Thrombolysis in Myocardial Infarction.
a
For some patients, only 1 blood draw is necessary.
b
For major adverse cardiac events (death, AMI, major arrhythmias).
c
Characteristics are provided for the hs-cTnT (Elecsys) and hs-cTnI (Architect). Cutoff levels differ for other hs-cTn assays becoming available for clinical use in the future.
5
6 Chang et al
Table 3
Risk stratification scores and established criteria for discharge from the emergency department
Abbreviations: ASA, acetylsalicylic acid; EDACS, Emergency Department Assessment of Chest Pain Score.
initially tested the score on 880 patients, yielding a much lower risk than those in the European
98.1% sensitivity, 41.6% specificity, and 99% studies, with an overall MACE of 6%. The sensi-
negative predictive value for major adverse cardio- tivity for MACE for 141 patients randomized to
vascular events (MACE) at 6 weeks. Validation the modified HEART pathway was 100%.43 The
studies conducted in Europe and Asian have TRAPID-AMI (The High Sensitivity Cardiac
shown sensitivities of 95% to 96%, and negative Troponin T Assay for Rapid Rule-out of Acute
predictive values of 98%.33,41 In the United States, Myocardial Infarction) study retrospectively incor-
Mahler and colleagues42 tested the HEART score porated a modified HEART score with hs-cTnT
on a registry cohort of 1070 patients. The score and, using the protocol, 515 or 1282 (40%) pa-
achieved a 58.3% sensitivity and an 85.0% spec- tients had a HEART score less than or equal to 3
ificity, with 5 MACE in the low-risk cohort. A small and negative delta troponin evaluations at
randomized controlled trial (RCT) used a modified 1 hour, with only one 30-day MACE (0.2%) in this
version of the HEART score that uses structured low-risk cohort. In patients with negative delta tro-
criteria to categorize history and excludes patients ponins but a HEART score greater than or equal to
from being classified as low risk if there is a posi- 4, the risk of MACE was more than 2%.44
tive troponin result from blood sampling at 0 and Other clinical decision rules have not been used
3 hours from arrival at the ED. This group was as frequently in the ED setting. The North
Chest Pain and Acute Coronary Syndromes 7
American Chest Pain Rule was 100% sensitive for has been found comparable with invasive angiog-
a cardiac event within 30 days and categorized raphy. Technological improvement has increased
18% of patients as safe for early discharge.38 sensitivity of detection of coronary artery stenosis
The model was internally validated using statistical from 84% for 4-slice computed tomography (CT)
bootstrapping techniques, but has not yet been to 83% for 16-slice CT to 93% for 64-slice CT,
validated in an external data set. with concurrent specificities from 93%, 96%, to
The Emergency Department Assessment of 96%, respectively.49 A systematic review of 41
Chest Pain Score (EDACS) Accelerated Diagnostic studies totaling 2515 patients indicated a sensi-
Pathway (ADP) was created with 2 goals: to develop tivity of 95% and specificity of 85% for detection
a risk stratification score, and then to pair this with 2- of CAD in all types of scanners combined.50 A
hour serial troponin testing to create a diagnostic report by the ESC and the European Council of
pathway. This protocol was validated and tested Nuclear Cardiology reporting a pooled analysis of
for reproducibility using prospectively collected 800 patients found a sensitivity of 89% (95% CI,
data from separate cohorts of patients from the 87–90) with a specificity of 96% (95% CI, 96–97)
same sites in Australia and New Zealand. An EDACS in 64-slice CT.51
less than 16 was considered low risk. In the ADP, the Budoff and colleagues52 compared the diag-
ECG had to have no new ischemic changes and nostic accuracy of coronary CTA with that of inva-
both 0-hour and 2-hour troponins were negative. In sive coronary angiography (ICA) in 230 patients.
the derivation and validation cohorts, the EDACS- On a per-patient basis, the sensitivity, specificity,
ADP classified more than 40% of patients as low and positive and negative predictive values to
risk.45 A subsequent validation of the EDACS-ADP detect greater than or equal to 50% stenosis
using a Canadian cohort of patients classified a were 95%, 83%, 64%, and 99%, respectively.
similar proportion of patients as low risk.46 The Miller and colleagues53 also compared the accu-
EDACS-ADP has now been validated in a RCT and racy of coronary CTA with ICA in 291 patients
is being used in multiple hospitals in New Zealand and found similar results. Further examples of
and Australia.47 However, a recent secondary anal- large studies comparing 64-slice coronary CTA
ysis of data collected in the United States attempted with ICA are shown in Table 1. These sensitivities
to validate these results, and found that the sensi- and specificities translate to a high negative pre-
tivity for MACE was only 88.2%.48 dictive value for low-risk to intermediate-risk pa-
Clinical decision aids with or without clinical tients in the ED.
gestalt have the potential to be important tools in Meijboom and colleagues54 evaluated the diag-
the assessment of patients presenting to the ED nostic utility of patients at high, intermediate, and
with possible AMI, and accelerated decision- low pretest risk of CAD. In the low pretest proba-
making processes incorporating such aids can be bility group, a negative coronary CTA was present
used to facilitate safe early discharge. Clinicians in 75% of the patients. The negative predictive
or departments thinking of adopting an ADP for value of coronary CTA to exclude significant CAD
local implementation should carefully decide on was excellent in these patients, reducing the esti-
the outcome of importance (ie, early rule-out of mated posttest probability to zero, and the investi-
AMI vs rule-out of ACS). Consideration should gators concluded that these patients would not
also be given to the prevalence of the disease in need further downstream diagnostic tests. Coro-
the hospitals where ADPs were studied. An ADP nary CTA was of limited clinical value in the evalu-
that was developed and tested in a low- ation of the group with high estimated pretest
prevalence population must be transferred with probability.
caution to a setting in which the disease preva-
lence is high and for this reason it is important to THIRTY-DAY EVENTS
consider both the sensitivity and the negative pre-
dictive value of the rule-out strategy. The pathways The literature shows that negative coronary CTA
based on ADAPT, EDACS, and HEART have the (defined as maximal stenosis <50% in all vessels)
most extensive evidence base behind them. is useful in the prediction of freedom from 30-day
cardiovascular events of MI, coronary revasculari-
zation, or death. In a recent meta-analysis of
DIAGNOSTIC TESTING
studies of 1559 patients with symptoms sugges-
Coronary Computed Tomography
tive of ACS who presented to EDs, the sensitivity
Angiography
was 93.3%, specificity was 89.9%, positive pre-
Large studies and meta-analyses have estab- dictive value was 48.1%, and negative predictive
lished the diagnostic accuracy of coronary value was 99.3% for 30-day cardiovascular
computed tomography angiography (CTA), and it events.55
8 Chang et al
without any stenosis greater than 50%, only 1 case patients who had a triple rule-out protocol per-
of unstable angina occurred during the initial formed. No further diagnostic testing was per-
90 days. Within a median of 18 months there formed in 133 (76%) of 175 of patients with no to
were only 4 events in these 802 patients (<0.5%), mild coronary disease within 30 days. Three cases
whereas there were 17 events in the 348 patients of pulmonary embolism were found, and 1 case of
(5%) with obstructive CAD. The ACRIN 4005 trial aortic dissection. Rogers and colleagues64 ran-
showed there was no difference in 1-year MACE domized patients to receive comprehensive
(1.4% vs 1.1%), ED revisits, hospital admissions, cardiothoracic CT or a coronary CTA in 59 pa-
or subsequent cardiac testing. There was only 1 tients. No significant difference was found in the
patient with a negative coronary CTA who had a median length of stay, rate of hospital discharge
MACE within the year.59 without additional imaging, costs of care, or the
Two smaller studies focused on low-risk to number of revisits between the dedicated and
intermediate-risk patients with chest pain. The comprehensive arms, respectively. Furthermore,
ROMICAT trial reported 2-year outcomes for their radiation dosages were similar between the two
cohort in 368 ED patients with acute chest pain, arms. Madder and colleagues65 identified patients
negative initial troponin, and a nonischemic who underwent triple rule-out or coronary CTA at 2
ECG. Cumulative probability of 2-year events hospitals in Michigan; 272 patients had triple rule-
increased across strata for CAD but none out and 1796 patients had coronary CTA per-
occurred in patients without disease (no CAD, formed. Pulmonary embolism was identified in
0%; nonobstructive CAD, 4.6%; obstructive only 1.1% of triple rule-out and 0.2% of cardiac
CAD, 30.3%).60 CT examinations, and there were no aortic dissec-
In a European cohort of 227 patients with 2.3- tions. At 90 days, there were no differences in
year follow-up, there were no cardiovascular death, ACS, pulmonary embolism, or aortic
events in the 96 patients without CAD (0%), 2 dissection diagnosis, or major differences in
events in the 76 patients with nonobstructive downstream resource use. Given that the radiation
CAD (2.6%), and 11 in the 55 patients (20%) with dose and intravenous contrast dose are higher in
obstructive CAD. Abdulla and colleagues con- triple rule-out scans, it does not seem to provide
ducted a meta-analysis that included 5675 pa- enough additional information to warrant the ex-
tients who were mostly intermediate to high risk amination in most patients.
in 10 studies with mean follow-up of 21 months.
The event rate was 0.5% in 2045 patients with SUMMARY
normal CTA, 3.5% in 2068 patients with nonob-
structive CAD, and 16% in the 1562 patients with It is imperative for providers to understand the
obstructive CAD. The CONFIRM (COroNary CT evidence-based decision making for chest pain
Angiography Evaluation For Clinical Outcomes: evaluation. Although the history and physical ex-
An InteRnational Multicenter Registry) multina- amination may be useful to identify other causes
tional registry includes more than 12,000 patients of chest pain, they are not useful for ruling in
from 12 sites in 6 countries.61 In patients without ACS. New improved cTn assays, used in conjunc-
CAD, the annualized MACE rate was only 0.31% tion with clinical decision rules, will help clinicians
versus 2.06% in those with obstructive disease.62 rapidly rule out a larger proportion of patients with
Thus it seems clear that a negative coronary potential ACS. Coronary CTA is now a proven
CTA is associated with a very low event rate and technology and should be incorporated into more
discharge directly from the ED is safe in the short chest pain rule-out pathways.
and longer term.
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