Graphical Abstract

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Today, chest pain is one of the most common reasons for attending primary and secondary care, and the attending clinician has multiple factors to consider.^[1] A key question is whether the symptoms are of cardiac origin. If yes, the symptoms may be classified as angina (typical or atypical) or non-anginal, e.g. pericarditis. Central chest pain that occurs with effort or physiological stressors and resolves with rest represents ‘typical angina’. The classical cause is obstructive coronary artery disease (CAD) but microvascular disease may equally cause typical angina. Symptoms such as effort-related breathlessness or spontaneous chest discomfort (not associated with effort) may arise secondary to myocardial ischaemia and be classified as ‘atypical angina’. Anginal symptoms that arise spontaneously are typical of coronary spasm. Age, sex, ethnicity, vascular risk factors (e.g. cigarette smoking, obesity), the environment (e.g. air pollution), and mental health, influence symptoms in individualized ways. Other causes of ischaemic symptoms include coronary vasomotion disorders (i.e. microvascular disease and coronary spasm),^[1] myocardial disease (e.g. hypertrophy), and systemic disorders (e.g. anaemia, hypertension, and renal disease).

A second priority is establishing the aetiology and whether symptoms are related to CAD. In this regard, computed tomography coronary angiography (CTCA) has strengths and limitations. Imaging of atherosclerosis is reliably achieved using non-invasive CTCA and invasive coronary angiography and to some extent by coronary magnetic resonance imaging. However, symptoms are more specifically assessed using a functional test. A diagnosis of coronary atherosclerosis serves as the basis for primary prevention including lifestyle measures and pharmacotherapy to modify risk factors and prognosis. Obstructive CAD should be treated with medical therapy and in patients with ischaemic symptoms, functional testing or invasive management coupled with physiological assessments should inform a decision for ischaemia-guided myocardial revascularization.

Computed tomography coronary angiography lacks resolution for small vessel disease. In order to diagnose microvascular angina, myocardial ischaemia testing using non-invasive techniques, e.g. stress testing with positron emission tomography or cardiovascular magnetic resonance (CMR), or invasive tests of coronary vascular function (functional coronary angiography), are required.

Most patients presenting to chest pain clinics do not have obstructive CAD,^[2,3]and most of these patients are women.^[3–6] An initial focus on excluding obstructive CAD leaves many patients with unexplained chest symptoms and uncertain management.^[4–6] The natural history of ischaemic heart disease (IHD) differs between men and women. Obstructive CAD is more likely in men^[2,3] whereas ischaemia with no obstructive coronary arteries (INOCA) (including microvascular angina and vasospastic angina) is more likely in women.^[4,5] In the prospective, all-comers CorMicA registry, which included 391 patients undergoing clinically indicated coronary angiography, compared with patients with obstructive CAD, physical limitation due to angina and quality of life were worse in patients with small vessel disease.^[5] Furthermore, use of functional tests in addition to angiography led to a reappraisal of the diagnosis and changes in treatment in half of the study population. The stratified medicine intervention in CorMicA linked test findings with mechanistically targeted therapy and improvements in symptoms and quality of life occurred over a 1-year period.^[5] In contrast, in the SCOT-HEART trial,^[7] angina and quality of life improved less in the CTCA-guided group compared with standard care. These results highlight that CTCA-guided management without functional testing is suboptimal for achieving symptom relief, in part because only a minority of individuals presenting with chest pain have obstructive CAD.

Clinical presentations may be caused by a stable chronic coronary syndrome^[8]or an acute coronary syndrome. IHD, CAD, and coronary heart disease (CHD) are not synonymous terms and should not be used interchangeably.^[8] They should be considered in a hierarchical classification system. IHD is positioned at the highest level, and the causes categorized as disease-specific subgroups (i.e. endotypes). Second-order terms include CHD and INOCA, and third-order terms are the specific causes of angina i.e. native CAD, restenosis, or endotypes of INOCA, e.g. microvascular angina and vasospastic angina, and non-coronary endotypes, e.g. left ventricular hypertrophy. A patient may have multiple pathologies. Standardized nomenclature is an important premise for unbiased decision-making.^[8]

Advances in medical technologies create new diagnostic possibilities. The data provided by an exercise test are clinically useful and prognostically validated^[9] but with limitations in test sensitivity and specificity for CAD. Advances in anatomical imaging of CAD using CTCA and in functional imaging of myocardial ischaemia using stress echocardiography, CMR, and nuclear imaging, are preferred options. Nonetheless, the treadmill exercise test remains clinically useful to assess a patient’s response to exercise, the reasons for ending a test, and the occurrence of symptoms and signs of ischaemia.^[10]

The question arises for clinicians (and their patients) ‘Which test to choose’ and for healthcare funders ‘Which scanner (or service) to provide?’ In the past decade, multiple clinical trials have been published and practice guidelines have followed.^[9,11,12] Other factors are deterministic for end-user adoption ‘in the clinic’. They include the cost of the technologies, their availability, contrast agents and staff expertise. Exposure to ionizing radiation is uniquely caused by CTCA and nuclear imaging, and the lifetime risk of cancer is relevant for younger patients and women. About 1 in 10 patients are unsuitable for CTCA due to atrial fibrillation, body size, coronary calcification, e.g. in the elderly, and intolerance of beta-blockers, i.e. asthma and left ventricular dysfunction.

Should clinicians adopt a default anatomical strategy or a more individualized approach? The anatomical approach using CTCA is recommended in the UK National Institute for Health and Care Excellence (NICE) clinical guideline 95.^[11]Personalized medicine takes account of the patient’s characteristics to stratify management and this approach is endorsed in the more recent clinical guidelines from the European Society of Cardiology^[9] and North American guidelines.^[12]

The editors of the European Heart Journal have posed the motion: ‘Great Debate: CTCA should be the initial diagnostic test in suspected angina‘. The pros and cons of this strategy are summarized in Table 1. Professor Kramer and colleagues write for the motion and Professor Kunadian and colleagues write against it. We hope you agree that the authors have captured the key issues.