REVIEW ARTICLE

Guidelines in review: Comparison of the 2014

AHA/ACC guideline for the management
of patients with non-ST-elevation acute
coronary syndromes and the 2015 ESC
guidelines for the management of acute
coronary syndromes in patients presenting
without persistent ST-segment elevation
Shane P. Prejean, MD,a Munaib Din, BSc,b Eliana Reyes, MD, PhD,b and
Fadi G. Hage, MD, FASNCa,c
a
Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at
Birmingham, Birmingham, AL
b
The PET imaging Centre at St. Thomas’ Hospital, King’s College London, London, UK
c
Section of Cardiology, Birmingham Veterans Affairs Medical Center, Birmingham, AL

Received Nov 12, 2017; accepted Nov 14, 2017

doi:10.1007/s12350-017-1137-z

In this Guidelines in Review, we review side-by-side the recommendations provided by the 2014
AHA/ACC Guideline for the management of patients with non-ST-elevation acute coronary
syndromes and the 2015 ESC Guidelines for the management of acute coronary syndromes in
patients presenting without persistent ST-segment elevation. We review the recommendations
for imaging in the evaluation of patients with possible ACS followed by the diagnostic evalu-
ation of patients with proven NSTE-ACS, based on their risk for adverse clinical events. (J Nucl
Cardiol 2017)
Key Words: Non-ST elevation acute coronary syndrome Æ non-invasive imaging Æ coronary
artery disease Æ stress testing

Abbreviations LAD Left anterior descending

ACS Acute coronary syndrome LOE Level of evidence
BMS Bare metal stent LV Left ventricular
CABG Coronary artery bypass grafting MPI Myocardial perfusion imaging
CAD Coronary artery disease NSR No specific recommendation
CKD Chronic kidney disease NSTE- Non-ST-elevation acute coronary
CT Computed tomography ACS syndrome
DES Drug-eluting stent PCI Percutaneous coronary intervention
ECG Electrocardiogram TEE Transesophageal echocardiography
GDMT Guideline-directed medical therapy TIMI Thrombolysis in myocardial infarction
GRACE Global Registry of Acute Coronary
Events
Reprint requests: Shane P. Prejean, MD, Division of Cardiovascular
Disease, Department of Medicine, The University of Alabama at
In this Guidelines in Review,1–9 we review side-by-
Birmingham, Lyons Harrison Research Building 306, 1900 Uni-
versity BLVD, Birmingham, AL 35294; sprejean@uabmc.edu side the recommendations provided by the 2014 AHA/
1071-3581/$34.00 ACC Guideline for the management of patients with
Copyright Ó 2017 American Society of Nuclear Cardiology. non-ST-elevation acute coronary syndromes10 and the
 Prejean et al. Journal of Nuclear CardiologyÒ
Guidelines in review: Comparison of the 2014 AHA/ACC guideline

Table 1. Recommendations for imaging in the immediate management of patients with possible ACS

AHA/ACC ESC class,

class, LOE LOE
Chest x-ray
Chest x-ray is useful to rule in or rule out differential diagnoses of chest pain NSR NSR
(i.e., pneumonia, pneumothorax, rib fractures, or other thoracic disorders) and
may show a widened mediastinum in patients with aortic dissection
Echocardiography
Echocardiography is recommended to evaluate regional and global LV NSR* I, C
function and to rule in or rule out differential diagnoses
Emergency echocardiography is recommended to assess LV and valvular NSR I, C
function and exclude mechanical complications in patients presenting with
acute heart failure and NSTE-ACS
Stress testing
It is reasonable for patients with possible ACS who have normal serial ECGs IIa, A/B NSR
and cardiac troponins to have an exercise ECG (LOE, A), stress myocardial
perfusion imaging (LOE, B) or stress echocardiography (LOE, B) before
discharge or within 72 hours after discharge
In patients with suspected ACS who have no recurrence of chest pain, normal NSR I, A
ECG findings, and normal levels of cardiac troponin (preferably high-
sensitivity), a non-invasive stress test (preferably with imaging) for inducible
ischemia is recommended before deciding on an invasive strategy
Imaging
In patients with possible ACS and a normal ECG, normal cardiac troponins, and IIa, A/B NSR
no history of CAD, it is reasonable to initially perform (without serial ECGs and
troponins) coronary CT angiography to assess coronary artery anatomy (LOE,
A) or rest myocardial perfusion imaging with a technetium-99m labeled tracer
to exclude ischemia. (LOE, B)
CT coronary angiography should be considered as an alternative to invasive NSR IIa, A
angiography to exclude ACS when there is a low to intermediate likelihood of
CAD and when cardiac troponin and/or ECG are inconclusive

From the ACC guidelines:

*Transthoracic echocardiography can identify a pericardial effusion and tamponade physiology and may also be useful to detect
regional wall motion abnormalities. Transesophageal echocardiography can identify a proximal aortic dissection. Because sig-
nificant valvular disease may also influence the type of revascularization, echocardiography rather than ventriculography is often
preferred for assessment of LV function.10

In low-risk patients with chest pain, CT angiography can be more cost-effective than stress myocardial perfusion imaging.
Coronary CT may increase rate of invasive angiography and revascularization in low-risk patients w/o ECG or troponin
alterations.10

2015 ESC Guidelines for the management of acute
coronary syndromes in patients presenting without per-
sistent ST-segment elevation.11 We review the
recommendations for imaging in the evaluation of
patients with possible ACS (Table 1) followed by the
diagnostic evaluation of patients with proven NSTE-
ACS, based on their risk for adverse clinical events
(Tables 2, 3, 4).
Two treatment pathways have emerged in both the
AHA/ACC and ECS guidelines for all patients with
NSTE-ACS. The invasive strategy triages patients to an
invasive diagnostic evaluation (i.e., coronary angiogra-
phy with intent to perform revascularization if
appropriate based on coronary anatomy). The invasive
strategy can be further divided into the immediate
invasive (\ 2 hours), early invasive (\ 24 hours), and
delayed invasive strategies (\ 72 hours).10,11
In contrast, the ischemia-guided strategy, as defined
by the AHA/ACC guidelines, calls for an invasive
evaluation for those patients who fail medical therapy
(refractory angina or angina at rest or with minimal
activity despite vigorous medical therapy), have objec-
tive evidence of ischemia as identified on a non-invasive
stress test (e.g., dynamic ECG changes, myocardial
perfusion defect) or who have clinical indicators of very
high prognostic risk (e.g., high TIMI or GRACE
Journal of Nuclear CardiologyÒ Prejean et al.
Guidelines in review: Comparison of the 2014 AHA/ACC guideline

Table 2. Recommendations for selection of invasive vs ischemia-guided or selectively invasive

strategies in patients with NSTE-ACS

AHA/ACC ESC class,

class, LOE LOE
Invasive strategies*
An immediate invasive strategy (\ 2 hours) is indicated in male and female I, A I, C
patients with at least one of the following very-high-risk criteria (without
serious comorbidities or contraindications to such procedures):
hemodynamic instability or cardiogenic shock
recurrent or ongoing chest pain refractory to medical treatment
life-threatening arrhythmias or cardiac arrest
mechanical complications of MI
acute heart failure with refractory angina or ST deviation
recurrent dynamic ST- or T-wave changes, particularly with intermittent ST-
elevation
An early invasive strategy (\ 24 hours) is recommended in initially stabilized I, B I, A
patients (without serious comorbidities or contraindications to such
procedures) with at least one of the following high-risk criteria:
none of the very-high-risk criteria mentioned above
rise or fall in cardiac troponin compatible with MI
dynamic ST- or T-wave changes (symptomatic or silent)
GRACE score [ 140
It is reasonable to choose an early invasive strategy (within 24 hours of IIa, B NSR
admission) over a delayed invasive strategy (within 25 to 72 hours) for initially
stabilized high-risk patients with NSTE-ACS. For those not at high/
intermediate risk, a delayed invasive approach is reasonable
An invasive strategy (\ 72 hours) is recommended in patients with at least one NSR I, A
of the following intermediate-risk criteria:
diabetes mellitus
renal insufficiency (eGFR \ 60 mL/min/1.73 m2)
LVEF \ 40% or congestive heart failure
early post-infarction angina
recent PCI
prior CABG
GRACE risk score [ 109 and \ 140, or recurrent symptoms or known
ischemia on non-invasive testing
An early invasive strategy is not recommended in patients with: III, C/C/B NSR
Extensive comorbidities (e.g., hepatic, renal, pulmonary failure; cancer), in
whom the risks of revascularization and comorbidities outweigh the
benefits of revascularization. (LOE, C)
Acute chest pain and a low likelihood of ACS who are troponin-negative
(LOE, C), especially women. (LOE, B)
Ischemia-guided strategy
In initially stabilized patients, an ischemia-guided strategy may be considered IIb, B NSR
for patients with NSTE-ACS (without serious comorbidities or
contraindications to this approach) who have an elevated risk for clinical
events
The decision to implement an ischemia-guided strategy in initially stabilized IIb, C NSR
patients (without serious comorbidities or contraindications to this
approach) may be reasonable after considering clinician and patient
preference
 Prejean et al. Journal of Nuclear CardiologyÒ
Guidelines in review: Comparison of the 2014 AHA/ACC guideline

Table 2 continued
AHA/ACC ESC class,
class, LOE LOE
Investigations to detect ischemia should be considered in patients presenting NSR IIa, C
with atrial fibrillation and elevated cardiac troponin levels.
Selective invasive strategy
In patients with none of the above-mentioned risk criteria and no recurrent NSR I, A
symptoms, a non-invasive stress test (preferably with imaging) for inducible
ischemia is recommended before deciding on an invasive strategy.,d

*Regarding an invasive strategy, the achievement of maximal hyperemia may be unpredictable in NSTEMI because of the
dynamic nature of coronary lesions and the associated acute microvascular dysfunction. As a result, fractional flow reserve (FFR)
may be overestimated and the hemodynamic relevance of a coronary stenosis underestimated. So far, the value of FFR-guided
PCI in this setting has not been properly addressed.11

Factors associated with appropriate selection of an ischemia-guided strategy include:
Low-risk score (e.g., TIMI [0 or 1], GRACE [\109]), Low-risk Tn-negative female patients, Patient or clinician preference in the
absence of high-risk features

Stress imaging is preferred over exercise ECG due to its greater diagnostic accuracy
d
Stress imaging modalities include stress echocardiography, stress cardiac magnetic resonance (CMR), and myocardial perfusion
imaging (resting, or combined stress-rest)

Table 3. Non-invasive testing in patients triaged to an ischemia-guided strategy

Risk stratification before discharge for patients with an AHA/ACC ESC class,
ischemia-guided strategy of NSTE-ACS: recommendations class, LOE LOE
Non-invasive stress testing is recommended in low- and intermediate-risk I, B NSR
patients who have been free of ischemia at rest or with low-level activity for a
minimum of 12 to 24 hours
Treadmill exercise testing is useful in patients able to exercise in whom the ECG I, C NSR
is free of resting ST changes that may interfere with interpretation
Stress testing with an imaging modality should be used in patients who are able I, B NSR
to exercise but have ST changes on resting ECG that may interfere with
interpretation. In patients undergoing a low-level exercise test, an imaging
modality can add prognostic information
Pharmacological stress testing with imaging is recommended when physical I, C NSR
limitations preclude adequate exercise stress
A non-invasive imaging test is recommended to evaluate LV function in patients I, C NSR
with definite ACS

scores).10 In the selective invasive strategy, as defined (preferably high-sensitivity) cardiac troponin level are at
by the ESC guidelines, patients with no recurrence of low risk of subsequent CV events. In this setting, a non-
chest pain, no signs of heart failure, no abnormalities in invasive stress test for inducible ischemia, preferably
the initial or subsequent ECG and no increase in with imaging, is recommended before deciding on an
Journal of Nuclear CardiologyÒ Prejean et al.
Guidelines in review: Comparison of the 2014 AHA/ACC guideline

Table 4. Evaluation and treatment of NSTE-ACS in special populations

AHA/ACC ESC class,

class, LOE LOE
In elderly patients
Treat older patients* with GDMT, an early invasive strategy, and I, A NSR
revascularization as appropriate
Undertake patient-centered management for older patients, considering I, B NSR
patient preferences/goals, comorbidities, functional and cognitive status, and
life expectancy
It is reasonable to choose CABG over PCI in older patients with NSTE-ACS who IIa, B NSR
are appropriate candidates, particularly those with diabetes mellitus or
complex 3-vessel CAD (e.g., SYNTAX score [ 22), with or without
involvement of the proximal LAD artery, to reduce cardiovascular disease
events and readmission and to improve survival
Elderly patients should be considered for an invasive strategy and, if NSR IIa, A
appropriate, revascularization after careful evaluation of potential risks and
benefits, estimated life expectancy, comorbidities, quality of life, frailty and
patient values and preferences
In patients with diabetes
Medical treatment in the acute phase of NSTE-ACS and decisions to perform I, A NSR
stress testing, angiography, and revascularization should be similar in patients
with and without diabetes mellitus
It is reasonable to choose CABG over PCI in older patients with NSTE-ACS who IIa, B NSR
are appropriate candidates, particularly those with diabetes mellitus or
complex 3-vessel CAD (e.g., SYNTAX score [ 22), with or without
involvement of the proximal LAD artery, to reduce cardiovascular disease
events and readmission and to improve survival
An invasive strategy is recommended over non-invasive management NSR I, A
In patients undergoing PCI, new-generation DES are recommended over BMS NSR I, A
In patients with stabilized multivessel CAD and an acceptable surgical risk, NSR I, A
CABG is recommended over PCI
In patients with stabilized multivessel CAD and a SYNTAX score B 22, PCI NSR IIa, B
should be considered as an alternative to CABG
In patients with CKD
Invasive strategy is reasonable in patients with mild (stage 2) and moderate IIa, B NSR
(stage 3) CKD
Coronary angiography and, if needed, revascularization are recommended NSR I, B
after careful assessment of the risk–benefit ratio, in particular with respect to
the severity of renal dysfunction
In patients undergoing PCI, new-generation DESs are recommended over NSR I, B
BMSs
CABG should be considered over PCI in patients with multivessel CAD whose NSR IIa, B
surgical risk profile is acceptable and life expectancy is [ 1 year.
PCI should be considered over CABG in patients with multivessel CAD whose NSR IIa, B
surgical risk profile is high or life expectancy is \ 1 year.
In patients with acute heart failure
 Prejean et al. Journal of Nuclear CardiologyÒ
Guidelines in review: Comparison of the 2014 AHA/ACC guideline

Table 4 continued
AHA/ACC ESC class,
class, LOE LOE
Early revascularization is recommended for cardiogenic shock due to cardiac I, B NSR
pump failure
Immediate coronary angiography is recommended in patients with acute heart NSR I, B
failure with refractory angina, ST deviation or cardiogenic shock
Immediate PCI is recommended for patients with cardiogenic shock if NSR I, B
coronary anatomy is suitable
Emergency CABG is recommended for patients with cardiogenic shock if the NSR I, B
coronary anatomy is not amenable to PCI
It is recommended to perform CABG without delay in patients with NSR I, C
hemodynamic instability, ongoing myocardial ischemia or very-high-risk
coronary anatomy, regardless of antiplatelet treatment
In patients with (chronic) heart failure
Patients with a history of heart failure should be treated according to the same I, B NSR
risk stratification guidelines and recommendations for patients without heart
failure
Selection of a revascularization strategy should be based on the extent of CAD, I, B NSR
associated cardiac lesions, LV dysfunction, and prior revascularization
In patients with CAD and LV ejection fraction B 35% following a NSTE-ACS, NSR IIa, B
testing for residual ischemia and subsequent revascularization should be
considered before primary prophylactic device implantation. After
revascularization, assessment of reverse LV remodeling up to 6 months
should be considered before device implantation
In patients with multivessel CAD
It is reasonable to choose CABG over PCI in older patients with NSTE-ACS who IIa, B NSR
are appropriate candidates, particularly those with diabetes mellitus or
complex 3-vessel CAD (e.g., SYNTAX score [ 22), with or without
involvement of the proximal LAD artery, to reduce cardiovascular disease
events and readmission and to improve survival
In patients with multivessel CAD, it is recommended to base the NSR I, C
revascularization strategy (e.g., ad hoc culprit-lesion PCI, multivessel PCI,
CABG) on the clinical status and comorbidities as well as the disease severity
(including distribution, angiographic lesion characteristics, SYNTAX score),
according to the local Heart Team protocol
In women
Early invasive strategy is recommended in women with NSTE-ACS and high- I, A NSR
risk features (troponin positive)
Women with low-risk features should not undergo early invasive treatment III, B NSR
because of lack of benefit and the possibility of harm

*Defined as those C 75 years of age in the AHA/ACC guidelines


This refers to implantable cardioverter defibrillators and cardiac resynchronization-defibrillator devices
Journal of Nuclear CardiologyÒ
Guidelines in review: Comparison of the 2014 AHA/ACC guideline
Figure 1. Summary of the diagnostic evaluation of patients with suspected or confirmed NSTE-ACS.
invasive strategy.11 The recommendations for the diag-
nostic evaluation of patients with suspected or confirmed
NSTE-ACS are summarized in Figure 1.
Disclosure
Dr. Hage has investigator-initiated grant support from
Astellas Pharma. Dr.’s Prejean and Reyes and Mr. Din have
nothing to disclose.
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