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The 2021 Chest Pain Guideline: A Revolutionary New Paradigm for Cardiac Testing

Editorials and Viewpoints

J Am Coll Cardiol Img, 15 (1) 140–144


The 2021 American Heart Association/American College of Cardiology/American Society of Echocardiography/CHEST/Society for Academic Emergency Medicine/Society of Cardiovascular Computed Tomography/Society for Cardiovascular Magnetic Resonance Guideline for the Evaluation and Diagnosis of Chest Pain has now been published (1). This multisociety guideline was developed by the American College of Cardiology and the American Heart Association along with other organizations and imaging societies, and it represents the first-ever U.S. or international guideline for the evaluation and diagnosis of patients with acute or stable chest pain. There are several noteworthy aspects to this new guideline (Figure 1) that will be of particular interest to cardiac imagers and clinicians who are involved in evaluating individuals with chest pain.

Figure 1
Figure 1

Novel Aspects of the 2021 Chest Pain Guidelines

CAD = coronary artery disease; CTA = computed tomography angiography.

Although it is well known that guideline-based recommendations are evidence based, the evidence used to support the use of cardiac imaging has traditionally been limited, as prior data evaluating the clinical effectiveness of imaging have mostly focused on diagnostic accuracy (and are often based on imperfect reference standards and across different patient populations) rather than on the impact of testing on patient management and outcomes. However, over the past decade, the quantity and quality of evidence supporting various clinical indications for noninvasive testing have grown substantially, especially for new imaging techniques. Consequently, the new guideline was based on a comprehensive and critical evaluation of the contemporary evidence base in imaging. When applying the available evidence, the writing group evaluated the quality of the evidence used to support different indications (ie, Level of Evidence [LOE]) and decided on the strengths of the recommendation based on the benefit and risk of each recommendation (ie, class of recommendation). Priority was given to randomized controlled clinical trials that evaluated patient outcomes, as well as the number of such trials conducted. In addition, a few other principles were used in forming the imaging-based recommendations: 1) imaging should be used selectively; 2) testing should be avoided when the diagnostic yield is low; 3) test layering should be avoided when possible; and 4) lower cost options should be prioritized when outcomes are similar.

Overview of Key Recommendations

The guidelines emphasize that the patients who are most likely to benefit from further testing are patients with acute chest pain who have an intermediate level of risk and those with stable chest pain who have an intermediate or high pretest probability of obstructive coronary artery disease (CAD). Specifically, the guidelines state that “for intermediate risk patients with acute chest pain and no known CAD who are eligible for cardiac testing, either exercise electrocardiography, stress echocardiography, stress PET/SPECT MPI, or stress CMR is useful for the diagnosis of myocardial ischemia” (Class 1; LOE: B, nonrandomized), whereas “CCTA is useful for exclusion of atherosclerotic plaque and obstructive CAD” (Class 1; LOE A). Among patients with acute chest pain, invasive angiography is recommended (Class 1; LOE C, expert opinion) in the presence of moderate to severe ischemia on a current or prior (≤1 year) stress test, or in the presence of high-risk CAD (left main ≥50% or 3-vessel ≥70% stenosis), or obstructive CAD (≥50%) and frequent angina. Invasive angiography is also suggested as an option if there is moderate to severe ischemia on an imaging stress test or abnormal fractional flow reserve–computed tomography (FFR-CT) imaging after coronary computed tomography angiography (CTA) with inconclusive stenosis or obstructive CAD.

With respect to patients with stable chest pain who do not have known CAD, the guidelines state that the use of a contemporary model to estimate the pretest probability of obstructive CAD (Class 1) or coronary artery calcium (CAC) testing (Class 2a, among low-risk patients) can be used to identify patients in whom further testing can be deferred. Importantly, and similar to the 2019 European Society of Cardiology Chronic Coronary Syndrome guideline (2), the chest pain guideline provides a contemporary model to estimate the pretest probability of obstructive CAD (Figure 11 in the guideline), as well as details on how information on the presence and severity of CAC can enhance this estimate. Among intermediate- to high-risk patients with stable chest pain and no known CAD, coronary CTA (Class 1; LOE: A) or stress imaging (stress echocardiography, positron emission tomography [PET]/single-photon emission computed tomography [SPECT], myocardial perfusion imaging [MPI], or cardiac magnetic resonance [CMR]; Class 1, LOE: B-R) are recommended as options. Among patients with stable chest pain with known CAD, the guideline recommends intensification of preventive therapies and an option to defer testing. In such patients, if there are persistent symptoms, coronary CTA is suggested as an option (Class 2a) if there is a history of nonobstructive CAD, whereas invasive angiography (Class 1 if high-risk CAD or frequent angina) or stress testing (Class 1 for all options except exercise electrocardiography Class 2a) are recommended.

Collectively, the aforementioned recommendations provided by the 2021 chest pain guideline offer a certain level of flexibility for clinicians, as ultimately most imaging tests have a Class 1 recommendation, albeit the clinical scenarios and LOE for each specific recommendation may vary to reflect the available effectiveness data for that technique. Notably, consensus for all recommendations was achieved by all writing group members (representative of all national imaging societies). Furthermore, the guideline underwent several rounds of peer review and was ultimately reviewed by >60 external reviewers.

Implications for Imagers

Although it is well recognized that imaging has an important role in the evaluation and management of patients with acute and chronic chest pain, the new chest pain guideline has important implications on when and how we should use cardiac testing.

First, imagers and clinicians need to be selective in deciding who requires further testing and avoid testing in those who are unlikely to benefit from additional investigations. When evaluating patients with acute chest pain, this can be accomplished by using various clinical decision pathways that integrate information on high-sensitivity troponin as well as other clinical variables to categorize patients into low-, intermediate-, and high-risk categories. Subsequently, low-risk patients would not require any further testing, whereas intermediate-risk patients may benefit from further noninvasive testing. Similarly, as described earlier, CAC testing in low-risk individuals and a contemporary pretest probability model of obstructive CAD can be used to identify stable patients in whom testing may be deferred. In fact, when evaluating the pretest probability of obstructive CAD table (Figure 11 in the guideline), all women aged <60 years and all men aged <40 years would be expected to have a pretest probability <15%. When testing is believed to be required in such low-risk patients, CAC or exercise treadmill testing (both Class 2a) may be options for the index evaluation.

Second, imagers need to promote effective use of testing by ensuring that unnecessary test layering is avoided. Clinicians should use the initial test results and severity and frequency of symptoms to intensify guideline-directed medical therapies and guide the need for follow-up testing. Consequently, among patients with stable chest pain, invasive angiography is mostly reserved for those who have high-risk anatomy or persistent symptoms. Similarly, among patients with acute chest pain, invasive angiography is reserved for those who have high-risk findings (eg, high-risk CAD, moderate- to severe-risk ischemia). The importance of optimizing guideline-directed medical therapies is emphasized across multiple scenarios and should be considered before invasive angiography.

Third, imagers need to be familiar with the strengths and limitations of different imaging approaches to ensure appropriate selection of the best test. In keeping with this principle, it is important to recognize the advantages of newer testing options (eg, plaque detection or FFR-CT imaging on coronary CTA [3], higher diagnostic accuracy and quantitative assessment of myocardial blood flow with PET, use of CMR for suspected myocardial infarction with nonobstructive coronary arteries). Although it is recognized that testing selection is influenced by local availability and expertise, the recommendations in this guideline should encourage sites that do not offer contemporary testing options to develop and implement such services. Ultimately, the recommendations of this and other guidelines are based on the available scientific data, rather than on local availability or economic factors. It is thus expected that evidence-based recommendations should ultimately drive clinical practice patterns and payment, rather than the other way around.

Finally, this guideline will also have implications on training of cardiovascular imagers, as they emphasize the importance of multimodality imaging as well as the need for lifelong learning to embrace new techniques while at the same time ensuring that value is derived from more established tests.

Focus on Contemporary Imaging Techniques

There are several examples of how the new chest pain guideline has ushered in a new focus on contemporary imaging. For instance, among intermediate- to high-risk patients in whom nuclear MPI is selected, PET is recommended in preference to SPECT (Class 2a), if available, to improve diagnostic accuracy and decrease the rate of nondiagnostic test results. FFR-CT imaging is suggested as a testing option following coronary CTA in patients with both stable and acute chest pain when there is 40% to 90% stenosis in a proximal or mid-vessel (Class 2a). Furthermore, coronary CTA and stress test options are presented for evaluating patients with various manifestations of nonobstructive plaque, a clinical entity that is increasingly common (4) and is now categorized as “known CAD” in this guideline. In recognition of the importance of atherosclerosis imaging, there is also a recommendation that “for patients with stable chest pain and no known CAD undergoing stress testing, the addition of CAC testing can be useful” (Class 2a). Also, there are important indications for the use of CMR among patients with suspected myocardial infarction with nonobstructive coronary arteries or acute myopericarditis (Class 1).

Although the guideline includes various recommendations that feature the use of contemporary imaging, older techniques that have an established role in patient management are also emphasized. For instance, the use of transthoracic echocardiography is recommended in several scenarios. For example, among intermediate-risk patients with acute chest pain, transthoracic echocardiography is recommended to establish baseline ventricular and valvular function, evaluate for wall motion abnormalities, and to assess for pericardial effusion (Class 1; LOE: C, expert opinion). Similarly, when evaluating the indications for stress testing, stress echocardiography and SPECT MPI remain important options with Class 1 recommendations across various scenarios.

Selecting Between Different Testing Options

Although many of the clinical scenarios in the chest pain guideline suggest that there are several different testing options, the writing group recognized that there are important differences between various options and provided suggestions on how to select between tests as well as a detailed list of contraindications for each modality (Table 5 of the guideline). Figure 6 of the guideline (“Choosing the right diagnostic test”) and the supporting text for the imaging sections provide criteria that may be useful in test selection. For instance, coronary CTA may be favored in those who are younger, are less likely to have obstructive CAD, or who have had a prior inconclusive functional study, whereas stress imaging may be favored in those who are older, are more likely to have obstructive CAD, or who have had a prior inconclusive coronary CTA. The guideline provides other compelling indications that may be considered when selecting between coronary CTA and stress imaging as well as specific information that may be obtained with different stress tests. For instance, although exercise treadmill testing, stress echocardiography, and SPECT MPI can provide information on exercise capacity, PET MPI and vasodilator stress CMR have the advantage of providing information on quantitative blood flow. Accordingly, these 2 techniques are suggested (Class 2a) as a noninvasive testing option for suspected ischemia with nonobstructive CAD.

In summary, the introduction of the 2021 chest pain guideline represents a revolutionary paradigm in how we use imaging to evaluate patients with known or suspected CAD. Ultimately, the impact of these guidelines will be based on the extent to which various recommendations are adopted across different clinical settings. At the same time, given the pace of current innovations, it will not be long until future advances in cardiac imaging and new clinical trials will reshape some of the recommendations that are now presented. As editors of iJACC and authors of the guideline, we look forward to engaging with imagers, clinicians, and researchers on how to best apply the recommendations made in this guideline as well as designing upcoming trials that will ultimately inform future clinical practice guidelines.

Funding Support and Author Disclosures

Dr Bhatt discloses the following relationships: advisory board, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; board of directors, Boston VA Research Institute, Society of Cardiovascular Patient Care, and ToBeSoft; chair, Inaugural Chair of the American Heart Association Quality Oversight Committee; Data Monitoring Committees, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Novartis, and Population Health Research Institute; honoraria, American College of Cardiology (Senior Associate Editor, Clinical Trials and News,; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and US national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); other, Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), and VA CART Research and Publications Committee (Chair); research funding, Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Lexicon, Lilly, Medtronic, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, and 89Bio; royalties, Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); site co-investigator, Abbott, Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Philips, and Svelte; trustee, American College of Cardiology; and unfunded research, FlowCo, Merck, and Takeda. Dr Blankstein discloses research funding from Amgen Inc and Novartis Inc; serves on the steering committee for Vesalius trial (Amgen); and is a consultant for Caristo Diagnostics Inc All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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