Much has changed in the decade since the 2012 Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease was published. There has been substantial advances in technology, a growing evidence base around diagnostic testing, and more emphasis placed on patient-centered care. The natural history of patients with stable coronary artery disease has also been better clarified, confirming frequent resolution of symptoms over time with a generally favorable prognosis.¹ These developments have ushered in a new era for the evaluation and management of the patient with chest pain and are well captured in the new 2021 American Heart Association/American College of Cardiology/American Society of Echocardiography/American College of Chest Physicians/Society for Academic Emergency Medicine/Society of Cardiovascular Computed Tomography/Society for Cardiovascular Magnetic Resonance Guideline for the Evaluation and Diagnosis of Chest Pain (GL).² Given the ubiquity of chest pain presentations across clinical settings, adoption of the new GL will affect primary care clinicians as well as cardiologists. This will create a new standard of care for chest pain evaluation of higher value—and possibly lower costs.

The title of the new GL includes “Chest Pain,” rather than the previous “Stable Ischemic Heart Disease,” emphasizing evaluation of symptoms rather than conditions. This is essential given the confounding heterogeneity of chest pain presentations and their implications. It also prioritizes meeting the patient’s needs early in the evaluation with shared decision making and guideline-directed medical management. Rather than working backwards to establish/exclude the unitary diagnosis of obstructive coronary artery disease, algorithms are prospective and aligned with usual progress of evaluations. The GL includes welcome recommendations for low-risk patients, a group previously given short shrift once coronary artery disease was excluded. Fundamental to this new approach is emphasis on patient engagement, with the phrase “shared decision making” used nearly 2 dozen times throughout. This replaces the previously used phrase “involvement of an informed patient” and is incorporated into evidence-based recommendations instead of expert consensus–based recommendations.

The new GL includes a remarkable amount of evidence for evaluation of chest pain from recent clinical trials.² The new GL also includes 8 Grade A recommendations instead of 1 in the previous GL; yet, this barely reflects the many other valuable recommendations across the spectrum of presentations and diagnoses. For evaluation of patients presenting with acute chest pain, recommendations have evolved from 24-h rule-out with serial biomarkers to early stress imaging to nearly immediate coronary computed tomographic angiography (CCTA) and now, high-sensitivity troponin.

For patients with stable chest pain, the GL follows the lead of European guidelines³ by assigning class 1, level-of-evidence A recommendations for initial testing to both CCTA (elevated from 2B or 2A if exercise intolerant) and stress imaging (from 2A, now including positron emission tomography and cardiovascular magnetic resonance imaging), with demotion of exercise ECG from Class 1 to 2A. Although some may argue the equivalence of functional and anatomic recommendations given SCOT-HEART (Scottish Computed Tomography of the HEART Trial) and other trial data indicating improved outcomes with CCTA, the GL takes a balanced middle path in providing support for CCTA while not discouraging usual, time-honored patterns of care with stress imaging.

Some new technologies included for the first time in the GL includes positron emission tomography (class 1) and attenuation correction (class 2B) in the nuclear field, and computationally based pressure gradient determination assessed by fractional flow reserve or fractional flow reserve derived from computed tomography (class 2A). Such tools assess hemodynamics and recognize the inadequacy of assessing stenosis alone, but require further investigation and validation. Other technologies previously considered cutting edge—particularly CCTA, cardiovascular magnetic resonance imaging, and coronary artery calcium scoring as an alternative (low risk) or adjunct to testing (intermediate-high risk) patient groups (both 2A)—are now mainstream. We can expect continued rapid evolution with ongoing advances including increased application of artificial intelligence techniques.

The new GL also introduces a new syndrome: ischemia with no obstructed coronary arteries (INOCA). Although the previous guidelines recognized the possibility of microvascular disease in diabetics and women, new data clarify that INOCA is common even among those with moderate to severe stress imaging abnormalities—up to one-third of excluded ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) patients with site-determined moderate to severe ischemia lacked significant stenosis on CCTA.⁴ Recognition by the GL means that INOCA is no longer a niche diagnosis and highlights the need for more data on the pathophysiology and treatment of this newly-recognized disorder, as being evaluated in CIAO-ISCHEMIA ([Changes in Ischemia and Angina Over One Year in ISCHEMIA Trial Screen Failures With INOCA] URL: https://www.clinicaltrials.gov; Unique identifier: NCT02347215) and the ongoing WARRIOR ([Women's Ischemia Trial to Reduce Events In Non-Obstructive CAD (coronary artery disease)]; URL: https://www.clinicaltrials.gov; Unique identifier: NCT03417388) trial.

Perhaps the most far reaching changes are in the determination of testing eligibility for those with stable chest pain that could shift the majority of those currently tested into a low-risk category in which testing is not recommended. This is conveyed by 2 subtle changes in the framing of the recommendations, not the recommendations themselves. The first is the use of contemporary coronary artery disease prevalence data to yield updated PreTest Probability (PTP) tables which are similar, but truncated when compared, to those adopted by the European guidelines.² The new PTP algorithm replaces the outdated Diamond–Forrester, which overestimates risk, as it was derived decades ago in much higher risk patients, before most current preventive therapies, and uses angiography or autopsy. The new PTP algorithm downgrades likelihood estimates by 50% to 70%, reclassifying most to a substantially lower risk category. For example, the new algorithm assigns a PTP <15% to all women <60 years old regardless of symptom type, whereas the previous 2012 GL classified women of any age with typical angina into a PTP >25%.² Similarly, PTP is now quite low at <4% in men <40 years old, regardless of symptoms, whereas the 2012 GL PTP in this age group was 76% for typical angina and 34% for atypical angina.

The second change addresses eligibility for testing, elevating the cut point for no testing or watchful waiting from those with a PTP <5% in 2012 to a PTP <15%. Since roughly one-half of current stable chest pain patients fall into the zone of 5% to 15% PTP using the revised tables,⁵ widespread adoption of this approach could result in substantial reductions in testing. When added to the reduction in PTP from the reformulated estimates, these changes may affect millions of patients. For comparison, the 2019 European Society of Cardiology guidelines consider 5% to 15% PTP as an intermediate zone in which testing is not proscribed but determined based on clinical factors, a strategy for which evidence is now accumulating.

Since both the PTP and testing eligibility changes are part of the recommendation-specific supportive text, they carry less force than formal recommendations and are less rigorously connected to the evidence base. Instead they are based on observations of low coronary artery disease prevalence and low event-rates in large study populations such as PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain),⁵ and the equivalence of guideline-directed medical management and revascularization in ISCHEMIA. However, the safety of a watchful waiting strategy in what were formerly considered intermediate-risk patients with class 1 indications for testing has never been tested prospectively. Randomized trial research (such as the ongoing PRECISE [Prospective Randomized Trial of the Optimal Evaluation of Cardiac Symptoms and Revascularization] trial; URL: https://www.clinicaltrials.gov; Unique identifier: NCT03702244) is urgently needed to confirm the safety and effectiveness of these potentially far-reaching changes.

In summary, the new GL incorporates important steps forward in patient centeredness, evidence-based care, and new technology. The focus on a broad array of symptoms earlier in the care process and emphasis on shared decision making and guideline-directed medical management represent important evolutions in care. The GL recognizes the prevalence and importance of INOCA for the first time, and draws on new evidence to elevate the use of anatomic testing while recognizing the enduring value of stress imaging. The GL also identifies several areas in need of additional research. These guidelines are an important step toward a systematic approach supported by evidence-based recommendations which will surely improve the care of patients with chest pain.

None.

Dr Douglas reports institutional research support from HeartFlow. Dr Alexander reports no conflicts of interest.

Nonstandard Abbreviations

CCTA	coronary computed tomographic angiography
GL	2021 American Heart Association/American College of Cardiology/American Society of Echocardiography/American College of Chest Physicians/Society for Academic Emergency Medicine/Society of Cardiovascular Computed Tomography/Society for Cardiovascular Magnetic Resonance Guideline for the Evaluation and Diagnosis of Chest Pain
INOCA	ischemia with no obstructed coronary arteries
ISCHEMIA	International Study of Comparative Health Effectiveness With Medical and Invasive Approaches
PTP	PreTest Probability

coronary computed tomographic angiography

2021 American Heart Association/American College of Cardiology/American Society of Echocardiography/American College of Chest Physicians/Society for Academic Emergency Medicine/Society of Cardiovascular Computed Tomography/Society for Cardiovascular Magnetic Resonance Guideline for the Evaluation and Diagnosis of Chest Pain

ischemia with no obstructed coronary arteries

International Study of Comparative Health Effectiveness With Medical and Invasive Approaches

PreTest Probability

The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.

For Sources of Funding and Disclosures, see page 1737.

Circulation is available at www.ahajournals.org/journal/circ

中文翻译：

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减少胸痛：更新并以患者为中心

自 2012 年稳定型缺血性心脏病患者诊断和管理指南发布以来，十年间发生了很大变化。技术取得了重大进展，围绕诊断测试的证据基础不断增加，并且更加强调以患者为中心的护理。稳定性冠状动脉疾病患者的自然病史也得到了更好的阐明，证实了随着时间的推移症状经常消退，预后普遍良好。¹这些发展为胸痛患者的评估和管理开创了一个新时代，并在新的 2021 年美国心脏协会/美国心脏病学会/美国超声心动图学会/美国胸科医师学会/学术协会中得到了很好的体现急诊医学/心血管计算机断层扫描学会/心血管磁共振评估和诊断胸痛 (GL) 指南。²鉴于临床环境中胸痛表现无处不在，采用新的 GL 将影响初级保健临床医生和心脏病专家。这将为胸痛评估创建一个新的护理标准，具有更高的价值，并且可能会降低成本。

新 GL 的标题包括“胸痛”，而不是以前的“稳定缺血性心脏病”，强调对症状而不是病情的评估。鉴于胸痛表现的混杂异质性及其影响，这是必不可少的。它还通过共享决策和以指南为导向的医疗管理优先考虑在评估早期满足患者的需求。算法不是向后工作以建立/排除阻塞性冠状动脉疾病的单一诊断，而是具有前瞻性并与通常的评估进展保持一致。GL 包括对低风险患者的欢迎建议，一旦排除了冠状动脉疾病，该组以前就被忽视了。这种新方法的基础是强调患者参与，“共同决策”这个词在整个过程中使用了近 2 次。这取代了以前使用的短语“知情患者的参与”，并被纳入基于证据的建议中，而不是基于专家共识的建议中。

新的 GL 包含大量来自最近临床试验的胸痛评估证据。²新的 GL 还包括 8 条 A 级建议，而不是之前的 GL 中的 1 条；然而，这几乎没有反映整个演示和诊断范围内的许多其他有价值的建议。对于急性胸痛患者的评估，建议已从使用系列生物标志物的 24 小时排除到早期压力成像，再到几乎立即的冠状动脉计算机断层扫描血管造影 (CCTA)，以及现在的高敏肌钙蛋白。

对于稳定性胸痛的患者，GL 遵循欧洲指南³的指导，将初始测试的 1 级证据水平 A 建议分配给 CCTA（如果运动不耐受，则从 2B 或 2A 提升）和压力成像（从 2A ，现在包括正电子发射断层扫描和心血管磁共振成像），运动心电图从 1 级降级到 2A 级。尽管考虑到 SCOT-HEART（苏格兰心脏计算机断层扫描试验）和其他表明 CCTA 改善结果的试验数据，有些人可能会争论功能和解剖学建议的等效性，但 GL 在为 CCTA 提供支持方面采取了平衡的中间路径，而不是阻止通常，历史悠久的压力成像护理模式。

GL 中首次包括的一些新技术包括核领域中的正电子发射断层扫描（1 类）和衰减校正（2B 类），以及通过计算断层扫描得出的分数流量储备或分数流量储备评估的基于计算的压力梯度确定（2A 类）。这些工具评估血流动力学并认识到单独评估狭窄的不足之处，但需要进一步调查和验证。以前被认为是尖端技术的其他技术——特别是 CCTA、心血管磁共振成像和冠状动脉钙评分作为替代（低风险）或辅助测试（中高风险）患者组（均为 2A）——现在已成为主流。

新的 GL 还引入了一种新的综合征：无阻塞冠状动脉的缺血 (INOCA)。尽管之前的指南承认糖尿病患者和女性患微血管疾病的可能性，但新的数据表明 INOCA 是常见的，即使在那些有中度至重度压力成像异常的人群中也很常见——高达三分之一的排除的 ISCHEMIA（国际医疗健康有效性比较研究）和侵入性方法）具有部位确定的中度至重度缺血的患者在 CCTA 上缺乏明显的狭窄。⁴GL 的认可意味着 INOCA 不再是一种利基诊断，并强调需要更多关于这种新发现疾病的病理生理学和治疗的数据，正如 CIAO-ISCHEMIA 中所评估的那样（[一年内缺血和心绞痛的变化） INOCA 的 ISCHEMIA 试验筛查失败] URL：https://www.clinicaltrials.gov；唯一标识符：NCT02347215）和正在进行的 WARRIOR（[减少非阻塞性 CAD（冠状动脉疾病）事件的女性缺血试验]；URL： https://www.clinicaltrials.gov；唯一标识符：NCT03417388）试验。

也许影响最深远的变化是确定那些患有稳定胸痛的人的测试资格，这可能会将目前接受测试的大多数人转变为不建议进行测试的低风险类别。这是通过建议框架的两个细微变化来传达的，而不是建议本身。第一个是使用当代冠状动脉疾病患病率数据来生成更新的预测试概率 (PTP) 表，该表与欧洲指南采用的表相似，但在比较时被截断。²新的 PTP 算法取代了过时的 Diamond-Forrester 算法，该算法高估了风险，因为它是几十年前在风险更高的患者中得出的，在大多数当前的预防性治疗之前，并使用血管造影或尸检。新的 PTP 算法将可能性估计值降低了 50% 至 70%，将大多数重新分类为风险大大降低的类别。例如，无论症状类型如何，新算法将 PTP <15% 分配给所有 <60 岁的女性，而之前的 2012 年 GL 将患有典型心绞痛的任何年龄的女性分类为 PTP >25%。²同样，无论症状如何，40 岁以下男性的 PTP 现在非常低，<4%，而 2012 年该年龄组的 GL PTP 为典型心绞痛为 76%，非典型心绞痛为 34%。

第二个变化涉及测试资格，将不测试或观察等待的临界点从 2012 年 PTP <5% 的人提高到 PTP <15%。由于使用修订后的表格，目前大约有一半的稳定胸痛患者的 PTP 处于 5% 至 15% 的范围内，⁵这种方法的广泛采用可能会导致检测的大幅减少。再加上重新制定的估计中 PTP 的降低，这些变化可能会影响数百万患者。相比之下，2019 年欧洲心脏病学会指南将 5% 至 15% 的 PTP 视为一个中间区域，在该区域中测试不被禁止，而是根据临床因素确定，这一策略目前正在积累证据。

由于 PTP 和测试资格变更都是特定于推荐的支持性文本的一部分，因此它们的影响力低于正式推荐，并且与证据基础的联系也不那么严格。相反，它们是基于在大型研究人群中观察到的低冠状动脉疾病患病率和低事件率，例如 PROMISE（用于评估胸痛的前瞻性多中心成像研究）⁵以及 ISCHEMIA 中指南指导的医疗管理和血运重建的等效性。然而，在以前被认为具有 1 类测试指征的中危患者中，观察等待策略的安全性从未进行过前瞻性测试。迫切需要随机试验研究（如正在进行的 PRECISE [Prospective Randomized Trial of the Optimal Evaluation of Cardiac symptoms and Revascularization] 试验；网址：https://www.clinicaltrials.gov；唯一标识符：NCT03702244）以确认安全性和这些可能影响深远的变化的有效性。

总之，新的 GL 在以患者为中心、循证护理和新技术方面向前迈进了重要一步。在护理过程的早期关注广泛的症状，强调共同决策和以指南为导向的医疗管理，代表了护理的重要演变。GL 首次认识到 INOCA 的普遍性和重要性，并利用新的证据来提升解剖测试的使用，同时认识到应力成像的持久价值。GL 还确定了几个需要进一步研究的领域。这些指南是朝着以循证为基础的建议支持的系统方法迈出的重要一步，这肯定会改善胸痛患者的护理。

没有任何。

Douglas 博士报告了 HeartFlow 的机构研究支持。Alexander 博士报告没有利益冲突。

非标准缩写

CCTA	冠状动脉计算机断层血管造影
总帐	2021 美国心脏协会/美国心脏病学会/美国超声心动图学会/美国胸科医师学会/学术急诊医学学会/心血管计算机断层扫描学会/心血管磁共振学会胸痛评估和诊断指南
伊诺卡	无阻塞冠状动脉的缺血
缺血	医学和侵入性方法比较健康效果的国际研究
点对点	预测概率

冠状动脉计算机断层血管造影

2021 美国心脏协会/美国心脏病学会/美国超声心动图学会/美国胸科医师学会/学术急诊医学学会/心血管计算机断层扫描学会/心血管磁共振学会胸痛评估和诊断指南

无阻塞冠状动脉的缺血

医学和侵入性方法比较健康效果的国际研究

预测概率

本文所表达的观点不一定是编辑或美国心脏协会的观点。

有关资金来源和披露信息，请参见第 1737 页。

流通可在 www.ahajournals.org/journal/circ