Education in Heart CHRONIC ISCHAEMIC HEART DISEASE Heart: first published as 10.1136/heartjnl-2018-314661 on 12 February 2020. Downloaded from Angina: contemporary diagnosis and management Thomas Joseph Ford ,1,2,3 Colin Berry 1 1BHF Cardiovascular Research INTRODUCTION Learning objectives Centre, University of Glasgow Ischaemic heart disease (IHD) remains the leading College of Medical Veterinary global cause of death and lost life years in adults, and Life Sciences, Glasgow, UK ► Around one half of angina patients have no 2 notably in younger (<55 years) women.1 Angina Department of Cardiology, obstructive coronary disease; many of these Gosford Hospital, Gosford, New pectoris (derived from the Latin verb ‘angere’ to patients have microvascular and/or vasospastic South Wales, Australia strangle) is chest discomfort of cardiac origin. It is a 3 angina. Faculty of Health and Medicine, common clinical manifestation of IHD with an esti- The University of Newcastle, ► Tests of coronary artery function empower mated prevalence of 3%–4% in UK adults. There Newcastle, NSW, Australia clinicians to make a correct diagnosis (rule- in/ are over 250 000 invasive coronary angiograms rule- out), complementing coronary angiography. Correspondence to performed each year with over 20 000 new cases of ► Physician and patient education, lifestyle, Dr Thomas Joseph Ford, BHF angina. The healthcare resource utilisation is appre- medications and revascularisation are key Cardiovascular Research Centre, ciable with over 110 000 inpatient episodes each aspects of management. University of Glasgow College year leading to substantial associated morbidity.2 In of Medical Veterinary and Life Sciences, Glasgow G128QQ, UK; 1809, Allen Burns (Lecturer in Anatomy, Univer- tom. ford@ health. nsw. gov. au sity of Glasgow) developed the thesis that myocar- dial ischaemia (supply:demand mismatch) could We begin by classifying angina according to patho- Published Online First explain angina, this being first identified by William physiology. We then consider the current guidelines 7 February 2020 Heberden in 1768. Subsequent to Heberden’s and their strengths and limitations for assessing report, coronary artery disease (CAD) was impli- patients with recent onset of stable chest pain. We cated in pathology and clinical case studies under- review non-invasive and invasive functional tests of taken by John Hunter, John Fothergill, Edward the coronary circulation with linked management Jenner and Caleb Hiller Parry.3 Typically, angina strategies. Finally, we point to future directions heart. bmj. com involves a relative deficiency of myocardial oxygen providing hope for improved patient outcomes and supply (ie, ischaemia) and typically occurs after development of targeted disease- modifying therapy. activity or physiological stress (box 1). The aim of this educational review is to provide a Six decades have passed since the first reported contemporary approach to diagnosis and manage- invasive coronary angiogram; however, many ment of angina taking into consideration epicardial physicians still consider detecting obstructive coronary disease, microcirculatory dysfunction and http://heart.bmj.com/ epicardial CAD on coronary angiography a ‘sine coronary vasospasm. qua non’ for the diagnosis of angina.4 The detec- tion of obstructive CAD allows evidence- based CONTEMPORARY ANGINA CLASSIFICATION BY medical treatment and consideration of myocar- PATHOPHYSIOLOGY dial revascularisation. However, underlying patho- The clinical history is of paramount importance physiology is more nuanced with contributions to initially establish whether the nature of the from anatomical atherosclerotic and/or functional presenting symptoms is consistent with angina alterations of epicardial vessels and/or microcir- (box 1). Indeed, recent data supports specialist on October 6, 2021 by guest. Protected copyright. culation (figure 1).5 ESC guidelines6 have revised physicians under- recognise angina in up to half of nomenclature (‘Chronic Coronary Syndromes’) in their patients.10 Furthermore, contemporary clinical part reflecting the importance of patients with signs trials of revascularisation in stable IHD including and symptoms of ischaemia without obstructive the ISCHEMIA trial highlight the importance of coronary artery disease—INOCA.7 8 Around half of good clinical history and listening to our patients to all patients with angina undergoing elective coro- determine the nature and frequency of symptoms nary angiography have no obstructive epicardial which helps to plan management. We propose a CAD.9 This large, heterogeneous chronic coronary classification of angina that aligns with underlying syndrome is comprised of distinct vasomotor disor- aetiology and related management (table 1). ders including microvascular angina (MVA) and/or vasospastic angina (VSA)—the two most common Angina with obstructive coronary artery disease underlying disorders of coronary vascular function 2018 ESC guidelines on myocardial revascularisa- in the INOCA population. Crucially, we stress that tion define obstructive CAD as coronary stenosis there are often multiple mechanisms of myocardial with documented ischaemia, a haemodynamically © Author(s) (or their ischaemia occurring in various coronary compart- relevant lesion (ie, fractional flow reserve (FFR) employer(s)) 2020. Re- use ments via different mechanisms. These frequently ≤0.80 or non-hyperaemic pressure ratio (NHPR) permitted under CC BY. coexist in combination; however, an appreciation (eg, iwFR≤0.89)) or >90% stenosis in a major Published by BMJ. of this fact can help stratify treatment and help us coronary vessel (table 1). There is renewed interest To cite: Ford TJ, Berry C. understand patients with poor treatment response in NHPRs (iwFR, resting full- cycle ratio (RFR) and Heart 2020;106:387–398. (eg, angina after revascularisation). diastolic pressure ratio (dPR)) as data have emerged Ford TJ, Berry C. Heart 2020;106:387–398. doi:10.1136/heartjnl-2018-314661 387 Education in Heart 32 Angina-myocardial ischaemia discordance Box 1 Definition of angina (NICE guidelines) Heart: first published as 10.1136/heartjnl-2018-314661 on 12 February 2020. Downloaded from Although obstructive CAD or microvascular dysfunction may be present, the link between isch- Typical angina: (requires all three) aemia and angina is not clearcut. The ‘ischaemic 1. Constricting discomfort in the front of the chest or in the neck, shoulders, threshold’ (the heart rate- blood pressure product at jaw or arms. the onset of angina) has intraindividual and interin- 2. Precipitated by physical exertion. dividual variability.14 Innate differences in vascular 3. Relieved by rest or sublingual glyceryl trinitrate within about 5 min tone and endocrine changes (eg, menopause) may – Presence of two of the features is defined as atypical angina. influence propensity to vasospasm while envi- – Presence of one or none of the features is defined as non-anginal chest ronmental factors including cold environmental pain. temperature, exertion and mental stress are rele- – Stable angina may be excluded if pain is non- anginal provided clinical vant. The large international CLARIFY registry suspicion is not raised based on other aspects of the history and risk highlighted the importance of symptoms, showing factors. that angina with or without concomitant ischaemia, – Do not define typical, atypical and non- anginal chest pain differently in was more predictive of adverse cardiac events men and women or different ethnic groups. compared with silent ischaemia alone.15 Other potential drivers of discordance between angina and ischaemia include variations in pain thresholds in support of numerical equivalency between these and cardiac innervation (eg, diabetic neuropathy). indices suggesting all can be used to guide treatment 11 strategy. Angina with underlying obstructive CAD Symptoms and/or signs of ischaemia but no allows symptom guided myocardial revascularisa- obstructive coronary artery disease (INOCA) tion (often with percutaneous coronary interven- Cardiologists are inclined to adopt a ‘stenosis tion (PCI)) and is effective in reducing ischaemic centric’ approach to patient management; however, burden and symptoms (in many patients). Recent as clinicians we must appreciate that all factors are studies have served evidence that functional coro- relevant, including coronary anatomy and function nary disorders overlap and may contribute to but systemic health and the psychosocial back- angina even in patients with obstructive epicardial ground (figure 2). First, systemic factors including CAD. Dynamic changes in lesion or vessel ‘tone’ heart rate, blood pressure (and their product) and and propensity to vasoconstriction is important and myocardial supply:demand ratio (Buckberg index) may cause rest angina that is frequently overlooked are relevant.16 Reduced myocardial oxygen supply 12 in patients with obstructive CAD. During invasive from problems such as anaemia or hypoxaemia physiological assessment of ischaemia during exer- should always be considered. cise, Asrress et al showed that ischaemia developed Second, coronary factors are well recognised but at FFR averaging≈0.76 which is not often observed certain nuances are overlooked. In 2018, the first 13 with adenosine induced hyperaemia. This finding international consensus guidelines clarify that a http://heart.bmj.com/ implies there are other important drivers of suben- definite diagnosis of MVA may be made in patients docardial