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Society for Cardiovascular Magnetic Resonance perspective on the 2021 AHA/ACC Chest Pain Guidelines

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Society for Cardiovascular Magnetic Resonance perspective on the 2021 AHA/ACC Chest Pain Guidelines

Araietal.
Journal of Cardiovascular Magnetic Resonance (2022) 24:8
https://doi.org/10.1186/s12968-021-00835-z
REVIEW
Society forCardiovascularMagnetic
Resonance perspective onthe2021 AHA/ACC
Chest Pain Guidelines
Andrew E. Arai1* , Raymond Y. Kwong2, Michael Salerno3, John P. Greenwood4 and Chiara Bucciarelli‑Ducci5
© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
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Society forCardiovascularMagneticResonance
perspective onthe2021 AHA/ACC Chest Pain
Guidelines
Diagnostic and treatment guidelines serve several impor-
tant purposes with an overall aim to improve medical
care. e 2021 American Heart Association (AHA)/
American College of Cardiology (ACC) Chest Pain
Guidelines [1, 2] represent a dramatic evolution from
the prior 2012 ACC/AHA Chest Pain Guidelines [3]. For
the practitioner that uses or performs cardiovascular
magnetic resonance (CMR), the release of new guide-
lines is an opportunity to reassess what we do, how we
do it, and how CMR should be used relative to other
imaging modalities. Guidelines translate scientific evi-
dence into recommendations on how to approach spe-
cific patient-related conditions. ough representing
the “state-of-the-art” at the time of publication, guide-
lines ultimately represent the opinions of experts in the
field and the quality of contemporaneous published lit-
erature. Inevitably, not all differences in opinion can be
incorporated. e Society for Cardiovascular Magnetic
Resonance (SCMR) endorsed the 2021 AHA/ACC Chest
Pain Guidelines as they accurately incorporate 15indi-
cations for CMR and capture a large proportion of what
CMR has to offer patients and clinicians in the evaluation
of acute and stable chest pain. is document aims to
summarize the new 2021 AHA/ACC Chest Pain Guide-
lines from an SCMR perspective, to highlight the current
role for CMR, to identify where knowledge gaps exist,
and to describe areas where some CMR expert opinions
may differ with the Guidelines. We hope this effort stim-
ulates debate and more importantly stimulates research
efforts to refine and expand appropriate CMR indications
in future international guidelines.
Indications forCMR inthe2021 AHA/ACC Chest
PainGuidelines
e 2021 AHA/ACC Chest Pain Guidelines include
many recommendations for the use of CMR which are
briefly summarized in the next paragraphs and figures.
is summary does not include non-CMR recommenda-
tions as the full guidelines are published in the Journal
of the American College of Cardiology [1] and Circula-
tion [2]. ey are also planned to be published later this
year in the Journal of Cardiovascular Magnetic Reso-
nance. Reviewing the full Guidelines is necessary to get
a detailed appreciation for how the various imaging
modalities are ‘weighted’ in particular recommendations.
Recommendation number from the full document is
included for reference (Fig.1).
Low risk coronary artery disease patients
For low-risk coronary artery disease (CAD) patients,
defined as those with a 30-day risk of death or major
adverse cardiovascular event (MACE) < 1%, the 2021
AHA/ACC Chest Pain Guidelines provide a class 2a
Open Access
*Correspondence: andrewarai@icloud.com
1 Private Consultant, Kensington, MD 20895, USA
Full list of author information is available at the end of the article
Page 2 of 8
Araietal. Journal of Cardiovascular Magnetic Resonance (2022) 24:8
recommendation indicating that it is reasonable to dis-
charge the patient home without hospitalization or
urgent cardiac testing. is is one of the “Top 10 Take-
Home Messages” of the updated guidelines.
Reducing imaging indications will reduce imaging
costs and the number of cardiac tests that confirm no
evidence of significant CAD. While an initial strategy
of no-testing is appropriate in these patients, test-
ing remains an option for patients with persistent or
worsening symptoms. From a CMR perspective, there
is time to schedule appropriate patients in a non-acute
setting rather than doing imaging as an emergency
procedure.
Intermediate risk patients withoutknown CAD
e 2021 AHA/ACC Chest Pain Guideline gives a
class I indication for stress CMR along with all other
stress imaging modalities among intermediate-risk
patients without known CAD (4.1.2.1.4). Stress imag-
ing, including CMR, is given a class 2a recommenda-
tion for sequential testing after an inconclusive coronary
computed tomography angiographic (CCTA) study
(4.1.2.1.7). e 2021 AHA/ACC Chest Pain Guideline
puts CMR on par with the other stress imaging modali-
ties regardless of whether or not a patient can exercise
or whether or not the electrocardiogram (ECG) is inter-
pretable (Fig.2).
Intermediate risk patients withknown CAD
For intermediate risk patients with acute chest pain and
known CAD, all stress imaging modalities are given a
class 2a recommendation (4.1.2.2.5) along with CCTA,
in patients with previously known non-obstructive CAD,
andwithout any preference of one modality over the oth-
ers. is recommendation also brings CMR to the same
level as the other non-invasive imaging modalities. Of
note, among those with known CAD, exercise testing with-
out imaging is no longer considered an appropriate study.
High‑risk patients withacute chest pain
ere is a class 2a recommendation for CMR or echocar-
diography to establish alternative diagnoses once obstruc-
tive CAD has been excluded by CCTA or invasive coronary
angiography (ICA). CMR has become well established for
detecting other pathologies such is myocardial infarction
with no obstructive coronary arteries (MINOCA) (4.2.3.1)
or myocarditis which can present acutely in the absence
of obstructive CAD (4.1.3.3). Stress CMR could also be
used to establish the diagnosis of ischemia in patientswith
noobstructive coronary arteries (INOCA) or microvascular
disease (5.2.2.3).
e 2021 AHA/ACC Chest Pain Guidelines favor com-
puted tomography (CT) as the first choice in the assessment
of possible acute aortic syndromes given its faster speed and
wider availability. CMR is given a class I recommendation
Fig. 1 Acute Chest Pain Recommendations for CMR [1, 2]. CAD coronary artery disease, CCTA coronary artery computed tomography angiography,
CMR cardiovascular magnetic resonance, ECG electrocardiogram, ICA invasive coronary angiography, MPI myocardial perfusion imaging, PET
positron emission tomography, SPECT single photon emission computed tomography
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Araietal. Journal of Cardiovascular Magnetic Resonance (2022) 24:8
as an alternative if CT is contraindicated or unavailable
(4.2.1.2).
In patients with possible myopericarditis (4.2.3.2), the
new guidelines give CMR a class I recommendation for
distinguishing myocarditis from other causes and for
assessing myocardial and pericardial inflammation and
fibrosis. ese recommendations align with increasing
community awareness of CMR as the test of choice for an
indication often labeled MINOCA. (4.2.3.1).
e 2021 AHA/ACC Chest Pain Guidelines also sup-
port a class 2a recommendation among patients with
acute chest pain and known or suspected valvular heart
disease if transthoracic echocardiography (TTE) or
transesophageal echocardiography (TEE) are not tech-
nically adequate for assessing valvular heart disease
(4.2.4.3). CMR has the ability to objectively quantify the
severity of regurgitant heart lesions (Fig.3).
Intermediate‑high risk patients withstable chest pain
andnoknown CAD
Among intermediate-high risk patients with stable
chest pain with no known CAD, CCTA and stress imag-
ing are given class I recommendations (5.1.3.2). Again,
CMR is not differentiated from the other stress imaging
modalities.
Stable patients withknown CAD
In patients with known obstructive CAD who have sta-
ble chest pain despite optimal therapy, stress imaging
receives a class I indication for diagnosing myocardial
ischemia, estimating risk of MACE, and guiding thera-
peutic decision making (5.2.1.5). ere is an additional
new class 2a indication for both PET and CMR add-
ing quantification of myocardial blood flow reserve
(MBFR) to improve diagnostic accuracy and enhance
risk stratification (5.2.1.8). is is particularly impor-
tant given the growing availability of CMR techniques
for performing absolute quantification of myocardial
blood flow.
In patients with known non-obstructive CAD, stress
CMR received a Class 2a recommendation for assess-
ing INOCA (5.2.2.3). Stress CMR with the addition
of quantitative myocardial blood flow assessment is
given a class 2a recommendation for the diagnosis of
coronary microvascular dysfunction and for assessing
MACE (5.2.3.3).
Fig. 2 Other Scenarios for Acute Chest Pain—Recommendations for CMR [1, 2]. CT computed tomography, MINOCA myocardial infarction with
no obstructive coronary arteries, TEE transesophageal echocardiography, TTE transthoracic echocardiography, VHD valvular heart disease. Other
abbreviations as in Fig. 1
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Araietal. Journal of Cardiovascular Magnetic Resonance (2022) 24:8
A case example fromthemeta‑analysis literature
(Knuuti etal. [4])
“In a 55-year old male patient with atypical angina
CCTA, single photon emission computed tomogra-
phy (SPECT), PET and stress CMR can reliably rule-
out anatomically significant CAD but stress ECG
or stress echocardiography cannot (A). To assess the
performance of imaging tests to detect functionally
significant CAD (assessed by fractional flow reserve
(FFR)) in the same patient (B) one can see that PET
and stress CMR results can both rule-out and rule-
in significant CAD while CCTA can only confidently
rule-out if a negative result is documented. ICA and
SPECT are not recommended tests in this patient.
(Fig.4)
Fig. 3 Stable Chest Pain Guidelines for CMR [1, 2]. INOCA, ischemia with no obstructive coronary arteries; MACE, major adverse cardiovascular
event; MBFR, myocardial blood flow reserve. Other abbreviations as in Figs. 1 and 2
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Araietal. Journal of Cardiovascular Magnetic Resonance (2022) 24:8
Disagreement withsome aspects oftheguidelines
The recommendations ofFFR‑CT are premature
e CCTA field recognizes that CCTA (and ICA) cannot
confidently rule-in functionally significant CAD and now
advocates fractional flow reserve (FFR)-CT to determine
functional significance of what is anatomically described
as “obstructive CAD” (50–90% stenosis) and extending
further to a 40% narrowing. A stress CMR may be more
cost-effective than FFR-CT or PET in sequential testing.
While, CCTA may be the best test to exclude anatomi-
cally significant CAD, PET and CMR can effectively rule-
in and rule-out functionally significant CAD.
e 2021 AHA/ACC Chest Pain Guidelines have 4 rec-
ommendations for FFR-CT in acute and chronic stable
chest pain syndromes and FFR-CT was broadly described
as an instrument for assessing likelihood of ischemia with
established robustness for decision-making in lesions
of 40–90% detected on CTA. FFR-CT was displayed in
numerous flow charts to represent equivalent class 2a
recommendations compared to any other functional
imaging modality.
However, the diagnostic and prognostic utilities of
FFR-CT are not as robustly evidenced as any of the
stress imaging modalities (stress CMR, SPECT, PET, and
stress echocardiography). FFR-CT does not improve the
sensitivity of CT, and only modestly improves the speci-
ficity of identifying flow-limiting obstructive coronary
artery lesions when compared with invasive FFR and
functional testing [58]. FFR-CT has only limited diag-
nostic accuracy in detecting hemodynamically significant
CAD in the intermediate range of coronary stenosis of
0.6–0.85 where management decisions are most needed
[7]. Studies evaluating FFR-CT have shown inferior
incremental diagnostic and prognostic value in compari-
son to functional testing [7, 9]. Additionally, the recent
FORECAST (Fractional Flow Reserve Derived From
Computed Tomography Coronary Angiography in the
Assessment and Management of Stable Chest Pain) trial
of over 1400 patients, while referral to invasive angiog-
raphy was lower, the use of FFR-CT did not demonstrate
any benefits in terms of healthcare costs, cardiovascular
outcomes, or quality of life compared to CT-alone [10].
Similarly, the recent RAPID-CT (Rapid Assessment of
Potential Ischaemic Heart Disease with CTCA) trial [11]
included 1748 patients with intermediate risk with sus-
pected or a provisional diagnosis of acute coronary syn-
drome randomised to Early CCTA and standard of care
compared with standard of care only. e study demon-
strated that early CCTA did not alter overall coronary
therapeutic interventions or one-year clinical outcomes.
Fig. 4 Ranges of clinical pre‑test probability in which each single‑positive test will confidently rule‑in (in orange) the presence of significant CAD
with post‑test probability > 85% or, conversely a negative test will confidently rule‑out CAD (in green) with post‑test probability < 15% [4]
Page 6 of 8
Araietal. Journal of Cardiovascular Magnetic Resonance (2022) 24:8
Furthermore, there are practical implications regard-
ing FFR-CT. FFR-CT is only feasible in a subset of CCTA
cases that are relatively artifact-free and remains highly
limited in patients with prior coronary artery stenting,
extensive calcification, severe valvular heart disease,
sequential luminal lesions or prior coronary artery bypass
graft surgery. FFR-CT is currently only available by a sin-
gle company (HEARTFlow, Redwood City, California,
USA). e CPT Category III code used to reimburse
FFR-CT is reserved for emerging technologies. Finally,
FFR-CT costs 3-times as much as a standard CCTA.
The ischemia imaging modalities were inappropriately
compared asagroup againstanatomical CCTA
e 2021 AHA/ACC Chest Pain Guidelines put all stress
imaging modalities in the same “functional imaging
group for the purpose of comparison against CCTA, as
shown in many flow charts and tables. is approach has
little clinical basis but also misses critical attributes of
different ischemia tests that may be relevant in the man-
agement of a vastly diverse patient spectrum. In the con-
temporary era, there is clear randomised trial evidence
for the use of stress CMR in reducing unnecessary ICA
referral or coronary revascularization rates, and thus
improving patient care, health outcomes and healthcare
resource utilization [12, 13].
e largest randomized trial to date, PROMISE (PRO-
spective Multicenter Imaging Study for Evaluation of
chest pain), prospectively evaluated the utility of an
anatomic (CCTA) testing approach in comparison with
functional testing (stress imaging and treadmill ECG test-
ing) amongst 193 North American centers in over 10,000
patients [14]. After a median of 2-years follow-up, no
differences in adverse cardiac outcomes were observed,
while the anatomic approach led to higher downstream
utilization of both ICA and coronary revascularization.
e SCOT-HEART (Scottish COmputed Tomography
of the HEART) trial conducted within the United King-
dom failed to meet its original primary endpoint, but did
observe a late reduction in non-fatal myhocardial infarc-
tion (MI) [15]. However, it was a trial of serial testing in
one arm (standard care using ETT plus CCTA) versus
standard of care (ETT only). is form of layered test-
ing might be expected to produce better outcomes, espe-
cially as exercise tolerancetesting (ETT) without imaging
is well recognized for lower sensitivity and specificity
than stress imaging tests. In addition, participants in the
SCOT-Heart trial were not systematically treated with
optimal medical therapy for primary prevention, a stand-
ard of care that has been part of modern cardiology prac-
tice for many years.
Denitions ofobstructive CAD, anatomically signicant
CAD, andfunctionally signicant CAD
e 2021 AHA/ACC Chest Pain Guidelines do not have
clear definitions of “Obstructive CAD”, “Anatomically
Significant CAD”, and “Functionally Significant CAD”.
ese three definitions overlap with each other and con-
tribute to miscommunication among healthcare provid-
ers and confuse patients. In general, the 2021 AHA/ACC
Chest Pain Guidelines do not systematically differentiate
anatomic CAD and functional CAD. is may contribute
to an overestimation of the utility of CCTA compared
with stress imaging modalities.
Fig. 5 Ten Take‑Home Messages for the Evaluation and Diagnosis of Chest Pain from an SCMR Perspective
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Araietal. Journal of Cardiovascular Magnetic Resonance (2022) 24:8
“Obstructive CAD” has been used to describe a 50%
or greater coronary artery diameter stenosis by quan-
titative coronary angiography (QCA) and is now widely
used to describe CCTA findings. However, the major-
ity of 50–70% stenoses are not severe enough to impair
coronary flow reserve [16]. Invasive FFR has been shown
in several multi-center trials to provide better outcomes
than management by stenosis severity [1719]. us,
“functionally significant CAD” represents the subset of
coronary artery stenoses that impair flow during vasodi-
lation or increased coronary flow demand. Stress imag-
ing tests are inherently designed to detect abnormal
flow reserve detected during exercise or pharmacologi-
cal stress. We believe the cardiology community should
work to clarifying terminology and avoid using words like
“obstructive” that suggest a physiological importance to
an anatomic stenosis that may or may not impair coro-
nary flow reserve.
Women’s health
e 2021 AHA/ACC Chest Pain Guidelines briefly
mention women-specific considerations in text but do
not make any formal recommendations that recognize
appropriateness or level of evidence. CCTA, SPECT, and
PET directly deliver radiation to the breasts. Now that
zero ionizing radiation methodologies like CMR can per-
form as well as CCTA and PET, and are superior to stress
echocardiography and SPECT, CMR seems the logical
choice for stress perfusion imaging in women if local
equipment and expertise is available.
Concluding thoughts anddirections forfuture
research
CMR has matured into a powerful diagnostic tool as evi-
denced by the wide range of clinical indications recog-
nized in the 2021 AHA/ACC Chest Pain Guidelines and
other international guidelines. Figure 5 summarizes 10
Take-Home Messages for the Assessment and Diagnosis
of Chest Pain—from a SCMR perspective. CMR practi-
tioners should continue to advocate the importance of
the functional significance of CAD.
e CMR community should be proud of the hard
work that provided the data leading to multiple Class I
and Class 2a Recommendations, which are now finally
more aligned with the 2014 ESC Guidelines on Revascu-
larization in which stress CMR features in Class IA rec-
ommendations [20]. However, more research is needed
regarding the comparative effectiveness of CMR rela-
tive to other stress imaging techniques and specifically,
CCTA. Randomized clinical trials comparing costs and
outcomes of different management strategies will be
important.
CMR and PET appear to have superior diagnostic accu-
racy compared with SPECT and stress echocardiography.
e relatively low specificity of CCTA for functionally
significant CAD is a weakness. e reliance on FFR-CT
to provide a computer-based substitute for a full physi-
ological assessment of CAD may or may not be cost-
effective over the long haul. CMR researchers should also
continue to refine quantitative methods as the current
Guidelines are the first to formally recognize the value
of quantifying myocardial blood flow reserve by CMR.
Studies focused on women will help highlight the role of
stress CMR versus other modalities in the diagnosis of
CAD as well as other causes of symptoms.
Abbreviations
ACC : American College of Cardiology; AHA: American Heart Association; CAD:
Coronary artery disease; CCTA : Coronary computed tomography angiography;
CMR: Cardiovascular magnetic resonance; CT: Computed tomography; ECG:
Electrocardiogram; ETT: Exercise tolerance test; FFR: Fractional flow reserve;
ICA: Invasive coronary angiography; INOCA: Ischemia with no obstructive
coronary arteries; MACE: Major adverse cardiovascular event; MBFR: Myocar‑
dial blood flow reserve; MI: Myocardial infarction; MINOCA: Myocardial infarc‑
tion with no obstructive coronary arteries; MPI: Myocardial perfusion imaging;
PET: Positron emission tomography; QCA: Quantitative coronary angiography;
SCMR: Society for Cardiovascular Magnetic Resonance; SPECT: Single photon
emission computed tomography; TEE: Transesophageal echocardiography;
TTE: Transthoracic echocardiography; VHD: Valvular heart disease.
Authors’ contributions
All authors helped develop the conceptual framework for the paper. AEA pre‑
pared the first draft. All authors provided critical review and edits. All authors
read and approved the final manuscript.
Funding
SCMR paid licensing fees to reuse previously published figures.
Availability of data and materials
All data and materials are in the public domain and thus available.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
All authors consent to publication of this work.
Competing interests
AEA has licensed software pertaining to perfusion quantification and a patent
pending. CBD is the Chief Executive Officer (part‑time) of the Society for Car‑
diovascular Magnetic Resonance (SCMR). Other authors did not identify any
competing interests directly related to the material in this editorial.
Author details
1 Private Consultant, Kensington, MD 20895, USA. 2 Brigham and Women’s
Hospital, Boston, MA, USA. 3 Stanford University, Palo Alto, CA, USA. 4 Leeds
Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds,
UK. 5 Royal Brompton Hospital, London, UK.
Received: 27 November 2021 Accepted: 30 November 2021
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Aim: This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients. Methods: A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Structure: Chest pain is a frequent cause for emergency department visits in the United States. The "2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain" provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. This guideline presents an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated, and shared decision-making with patients is recommended.
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Aim This executive summary of the clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients. Methods A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Structure Chest pain is a frequent cause for emergency department visits in the United States. The “2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain” provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. These guidelines present an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated and shared decision-making with patients is recommended.
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Aim This clinical practice guideline for the evaluation and diagnosis of chest pain provides recommendations and algorithms for clinicians to assess and diagnose chest pain in adult patients. Methods A comprehensive literature search was conducted from November 11, 2017, to May 1, 2020, encompassing randomized and nonrandomized trials, observational studies, registries, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Additional relevant studies, published through April 2021, were also considered. Structure Chest pain is a frequent cause for emergency department visits in the United States. The “2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guideline for the Evaluation and Diagnosis of Chest Pain” provides recommendations based on contemporary evidence on the assessment and evaluation of chest pain. This guideline presents an evidence-based approach to risk stratification and the diagnostic workup for the evaluation of chest pain. Cost-value considerations in diagnostic testing have been incorporated, and shared decision-making with patients is recommended.
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Objectives The aim of this study was to compare the incremental prognostic value of coronary computed tomography (CT) angiography (CCTA)-derived machine learning fractional flow reserve CT (ML-FFRct) versus that of ischemia detected on single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI) on incident cardiovascular outcomes. Background SPECT MPI and ML-FFRct are noninvasive tools that can assess the hemodynamic significance of coronary atherosclerotic disease. Methods We studied a retrospective cohort of consecutive patients who underwent clinically indicated CCTA and SPECT MPI. ML-FFRct was computed using a ML prototype. The primary outcome was all-cause mortality and nonfatal myocardial infarction (D/MI), and the secondary outcome was D/MI and unplanned revascularization, percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) occurring more than 90 days postimaging. Multiple nested multivariate cox regression was used to model a scenario wherein an initial anatomical assessment was followed by a functional assessment. Results A total of 471 patients (mean age: 64 ± 13 year; 53% males) were included. Comorbidities were prevalent (78% hypertension, 66% diabetes, 81% dyslipidemia). ML-FFRct was <0.8 in at least 1 proximal/midsegment was present in 41.6% of patients, and ischemia on MPI was present in 13.8%. After a median follow-up of 18 months, 7% of patients (n = 33) experienced D/MI. On multivariate Cox proportional analysis, the presence of ischemia on MPI but not ML-FFRct significantly predicted D/MI (HR: 2.3; 95% CI: 1.0-5.0; P = 0.047; or HR: 0.7; 95% CI: 0.3-1.4; P = 0.306 respectively) when added to CCTA obstructive stenosis. Furthermore, the model with SPECT ischemia had higher global chi-square result and significantly improved reclassification. Results were similar using the secondary outcome and on several sensitivity analyses. Conclusions In a high-risk patient cohort, SPECT MPI but not ML-FFRct adds independent and incremental prognostic information to CCTA-based anatomical assessment and clinical risk factors in predicting incident outcomes.
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Background Although coronary computed tomographic angiography (CTA) improves diagnostic certainty in the assessment of patients with stable chest pain, its effect on 5-year clinical outcomes is unknown. Methods In an open-label, multicenter, parallel-group trial, we randomly assigned 4146 patients with stable chest pain who had been referred to a cardiology clinic for evaluation to standard care plus CTA (2073 patients) or to standard care alone (2073 patients). Investigations, treatments, and clinical outcomes were assessed over 3 to 7 years of follow-up. The primary end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years. Results The median duration of follow-up was 4.8 years, which yielded 20,254 patient-years of follow-up. The 5-year rate of the primary end point was lower in the CTA group than in the standard-care group (2.3% [48 patients] vs. 3.9% [81 patients]; hazard ratio, 0.59; 95% confidence interval [CI], 0.41 to 0.84; P=0.004). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTA group than in the standard-care group in the first few months of follow-up, overall rates were similar at 5 years: invasive coronary angiography was performed in 491 patients in the CTA group and in 502 patients in the standard-care group (hazard ratio, 1.00; 95% CI, 0.88 to 1.13), and coronary revascularization was performed in 279 patients in the CTA group and in 267 in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91 to 1.27). However, more preventive therapies were initiated in patients in the CTA group (odds ratio, 1.40; 95% CI, 1.19 to 1.65), as were more antianginal therapies (odds ratio, 1.27; 95% CI, 1.05 to 1.54). There were no significant between-group differences in the rates of cardiovascular or noncardiovascular deaths or deaths from any cause. Conclusions In this trial, the use of CTA in addition to standard care in patients with stable chest pain resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years than standard care alone, without resulting in a significantly higher rate of coronary angiography or coronary revascularization. (Funded by the Scottish Government Chief Scientist Office and others; SCOT-HEART ClinicalTrials.gov number, NCT01149590.)