Kevin F Fox. Coronary disease INVESTIGATION AND MANAGEMENT OF CHEST PAIN

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1 Coronary disease INVESTIGATION AND MANAGEMENT OF CHEST PAIN EPIDEMIOLOGY Correspondene to: Dr Kevin F Fox, Department of Cardiology, Hammersmith Hospitals NHS Trust at Charing Cross Hospital, Fulham Palae Rd, London W6 8RF, UK; k.fox@imperial. a.uk C Kevin F Fox Heart 2005; 91: doi: /hrt hest pain is the most ommon presenting symptom of oronary heart disease (CHD). The effetive assessment and management of patients with hest pain is entral to any strategy to redue the burden of oronary disease. Furthermore the investigation of patients with hest pain absorbs a substantial proportion of the resoures of ardiologists and their departments. The simple fats of taking a history to eliit features of ishaemi pain, examining and then investigating using established proedures suh as exerise testing, funtional imaging, and angiography are well desribed in any textbook of mediine or ardiology. Indeed these will be well known to medial students. The hallenge to senior liniians is to synthesise a servie that brings these priniples to the patient in a timely, aessible, onsistent, and ost onsious format to provide an effetive servie that takes patients within the population to the orret diagnosis and then onwards along their journey to evidene based treatments. This artile will therefore fous on how to organise servies so that the full spetrum of patients with hest pain are assessed in the right way, in the right environment, and in the right time frame. Overall the evidene base for the way we organise servies is limited and mainly observational, but the use of randomised trials is gaining a foothold. This artile will take the subjet of hest pain through assessment and investigation with a partiular fous on CHD. OF CHEST PAIN Annually it is estimated that there are primary are onsultations for angina eah year. The overall ost of aring for angina was alulated to be around 1% of the UK National Health Servie (NHS) budget. 1 The burden of hest pain is far greater than the burden of angina. Nilsson and olleagues report from Sweden that 1.5% of primary are onsultations are for hest pain, but only 17% of these are assoiated with definite or possible angina. 2 A reent epidemiologial study from South East London has provided ontemporary data on the presentation of CHD (fig 1). The most ommon first presentation of CHD is exertional angina. Less than 14% present with sudden death, and 54% of men and 65% of women have preserved myoardium at presentation. 3 So opportunities to offer effetive seondary preventive treatment exist for most ases of CHD; for the majority, left ventriular (LV) damage, whih is one of the most powerful adverse prognosti features, is not present at first presentation. Data from Gandhi and olleagues 4 show that if evidene based treatments are to be used effetively, they must be introdued promptly. In their study of ases of new exertional angina, 10% of patients suffer death or infartion in the first year (besides another 20% who undergo revasularisation), an event rate that falls dramatially thereafter. 4 Within the UK overall CHD mortality is falling. There are also data on the falling prevalene of anginal symptoms. In the British regional heart study of 7735 men aged years at entry, and monitored from 1978 to 1996, the prevalene of anginal symptoms has fallen by 1.8%, although the prevalene of a diagnosis of CHD is essentially unhanged. 5 The authors suggest that several fators may be at work here. Diagnosti thresholds may have fallen suh that less severe disease is identified. The inreasing numbers of patients being diagnosed with angina in rapid aess hest pain linis (RACPCs) supports this. Angina, as the presentation of CHD, may be delining (unlikely from reent data). A third option is that the linial ourse of angina is beoming more benign through a mixture of population fators and the introdution of more effetive treatments, therefore reduing the symptom burden of those with angina. ACCESS TO CARE If patients do not aess are for example, by not presenting to health are servies or are not able to fully partiipate in are, then outomes will be suboptimal both for the individuals onerned and for the population. Barriers to full and equitable aess an be related to patients, physiians, and servies. Patient fators may inlude language, ulture, and soioeonomi status. Physiian fators inlude inequitable referral patterns while omplexities, biases, and queues in 105 Heart: first published as /hrt on 16 Deember Downloaded from on 16 Otober 2018 by guest. Proteted by opyright.

2 106 Figure 1 women. 3 The presentation of oronary heart disease in men and the servie may mean that aessing are is more a test of skill in navigating the system than linial need. Rihards and olleagues 6 showed that patients from a more deprived area of Glasgow reported greater pereived vulnerability to heart disease, but did not present beause of fears they would be blamed by general pratitioners for their risk behaviour and a sense that they already overused medial servies. A further qualitative study by Gardner and olleagues 7 of stable angina patients in Liverpool showed that patients pereived themselves as old, had low expetations of treatment, knew little of reent advanes, feared hospitals and tests, and saw dotors as busy. Cliniian and servie based inequalities in aess follow patients through their journey. Distane from the ardia atheter lab influened referral for oronary angiography, based on data from a Danish study. 8 In a UK study older patients and women were shown to be less likely to be referred for exerise testing and subsequent angiography despite appropriate indiations. 9 This study also showed underuse of angiography based on urrent aepted indiations aross all patient groups. Simple expansion of servies is unlikely to resolve problems of aess without speifi measures to address inequalities and barriers. PRIMARY CARE SERVICES There is inreasing diversity in primary are servies for the assessment of hest pain. Patients may hoose between their own primary are pratitioner, walk-in entres, NHS Diret (a telephone based advie servie in the UK), a hospital emergeny department, and dialling for an ambulane. These servies provide the primary point of ontat for patients and an important filter, so their effetiveness, and their integration with seondary are servies, is key to a suessful patient journey. Grant and olleagues 10 ompared quality of assessment of several sample patients, inluding one with hest pain, between walk-in entres, standard primary are, and NHS Diret. NHS Diret referred onwards the highest proportion (82% v 26% onward referral for walk-in entres). Based on an overall sore derived by the authors, walk-in entres, whose key feature is to use a protool based assessment proess, performed most favourably. SECONDARY CARE SERVICES A variety of models of seondary are servies may exist for the assessment of suspeted exertional angina referred from primary are, but the most signifiant development has been the establishment of foused linis or RACPCs. 11 Although first developed to support epidemiologial researh, their potential to improve servie provision was soon reognised. Within the UK suh linis were given a substantial finanial boost through their designation as the servie model of hoie in the National Servie Framework for CHD. They provide prompt aess to diagnosis, risk stratifiation, and treatment initiation for suspeted angina. Compared to traditional outpatients they employ foused, standardised, onsistent rather than omplex assessment, and typially they are staffed by non-onsultant grade physiians or nurses (fig 2). Diret aess exerise testing has fallen in popularity as a model of servie, refleting a general view of primary are that the preferred servies to support primary are are speialist direted and ontextualised investigation. In the related area of suspeted heart failure Fuat and olleagues 12 desribed, in a qualitative study of primary are pratitioners in north east England, onerns with a servie based on open aess investigation. Observational data onsistently support the effetiveness of RACPCs and overall suggest that risk stratifiation is effetive, admissions are saved, and osts redued. Dougan and olleagues 13 report no ardia events among 395 patients diagnosed as having non-ardia pain within three months of attendane at an RACPC in Belfast and a ost saving of 58 per patient ompared to usual are. Newby and olleagues from Edinburgh presented data on GP management with and without an RACPC and reported a 46% redution in admissions. 14 However, no trials have ompared RACPCs with other models, and the main finding of a meta-analysis of studies on RACPCs was to highlight the sparsity of data. 15 Heart: first published as /hrt on 16 Deember Downloaded from on 16 Otober 2018 by guest. Proteted by opyright.

3 Atypial history and low risk for CHD Reassure and disharge -ve ET Still suspiious: trial of treatment or further Ix Overall low risk: reassure Possible or definite exertional angina Proeed to exerise test (ET) Low risk: Initial medial treatment NON-INVASIVE ASSESSMENT OF CHEST PAIN Adequate history taking is essential to evaluate suspeted ardia hest pain. The priority is to identify ishaemi pain. The ore features that diagnose exertional angina are readily aessible from a straightforward assessment of the patient and the pain (table 1). Cooke and olleagues 16 examined the desription of pain in 65 patients with normal angiograms ompared to 65 with signifiant oronary stenosis. The presene of two out of three of (1) pain duration, 5 minutes, (2) rest pain, 2/10 episodes, (3) 10/10 episodes being reprodued by a similar level of exertion was noted in 85% with signifiant disease while in only 26% of those with normal angiograms. 16 Resting physial examination and a 12 lead ECG are essential omponents of the assessment of hest pain, although in suspeted exertional angina they are usually normal. Exerise tolerane testing with ontinuous 12 lead ECG monitoring is the primary non-invasive test for the evaluation of suspeted ishaemi hest pain. There are widely published reviews and guidelines for its ondut and interpretation 17 ( Patient registration PIS, questionnaire height, weight, BP, blood tests, ECG history and examination +ve ET Aspirin, ß bloker (CCB if CI) Address risk fators (BP, lipids, et) Risk stratify (patient profile, ET) High risk: Coronary angiography Possible ACS Consider admission Equivoal ET / ET not possible Further Ix Thallium/ DSE/ angiography Trial of treatment or observe & review Figure 2 Core protool for a rapid aess hest pain lini (RACPC). Adapted from Sutliffe and olleagues. 11 ACS, aute oronary syndrome; BP, blood pressure; CCB, alium hannel bloker; CI, ontraindiated; DSE, dobutamine stress ehoardiogram; Ix, investigation; PIS, patient information sheet. Table 1 Features of hest pain aused by oronary heart disease (CHD) Features in the patient family history of CHD (male first degree relative,55 years old, female,60 years old) hyperlipidaemia hypertension diabetes Features to seek in the pain harateristis (and typial answers) loation: entral (radiating to left arm and throat) harater: tight, squeezing, onstriting duration:,5 minutes worsened by exertion (physial but also emotional) relieved by rest (or nitrates) Exerise testing enapsulates a fundamental priniple of all investigations the appliation of Baye s theorem. For exerise tests this manifests in the statement that the posttest likelihood of CHD depends both on the test result and the pre-test likelihood of CHD. Exerise testing is simple, safe (mortality 1 in ), and a widely appliable test, and has a valuable 78% sensitivity and 70% speifiity for deteting CHD. But in pratie the outome an be even more helpful. A negative exerise test at adequate workload in patients with low to moderate pre-test probability of CHD effetively eliminates the likelihood of signifiant CHD. Suh patients form a signifiant proportion of the workload of many RACPCs and their investigation should stop and reassurane begin following the exerise test. Exerise testing outomes are not abnormal or normal but ontinuous variables in exerise duration, physiology, and ECG hanges. Careful study of all the parameters measured is needed if the pre-test probability of CHD is to be appropriately adjusted. Despite the usefulness of exerise testing, a substantial number of patients do not have their diagnosis and risk fully determined by an exerise test, or are unable to perform an adequate test. Additional non-invasive investigations (often loosely grouped as funtional tests ) bridge the gap between exerise testing and invasive assessment. Exellent reviews of stress ehoardiography and myoardial perfusion imaging have been published in this series. Suh reviews, ombining multiple studies, report a sensitivity and speifiity for dobutamine stress ehoardiography of 81% and 80%, and for perfusion imaging. 90% and 70% (table 2). Physiologial rather than pharmaologial stress improves sensitivity. Importantly a negative study using either modality predits a, 1% major event rate over the subsequent few years. The reent National Institute for Clinial Exellene (NICE) guidelines on myoardial perfusion imaging did not onsider other modalities, but in many ways are a template for provision of funtional testing in general, rather than speifi to nulear ardiology (table 3) (www. nie.org.uk). 107 Heart: first published as /hrt on 16 Deember Downloaded from on 16 Otober 2018 by guest. Proteted by opyright.

4 108 Table 2 Stress ehoardiography versus perfusion imaging. Adapted from Marwik 18 N Diagnosis of CHD N Prognosti evaluation N Detetion of myoardial viability Similar auray in meta-analyses and head-to-head trials Stress eho less sensitive for mild disease Perfusion sanning less speifi Similar (very good) prognosti impliations of a negative test Stress eho less sensitive but more speifi for predition of long term reovery The optimal integration of funtional testing into a hest pain assessment pathway relies on appreiating both the test and the harateristis of the patients likely to be referred. In many assessment algorithms patients referred for funtional testing have a low to moderate pre-test probability of CHD, are often poorly mobile with raised body mass index, and not optimal for exerise testing or funtional imaging. In ontrast high pre-test probability patients are referred diretly for angiography. So the sensitivity and speifiity of these investigations may be lower than published data. Intense quality ontrol is essential and partiularly so if the investigation rosses boundaries between ardiology and radiology. Newer modalities of imaging (ardia magneti resonane (CMR) and omputed tomography (CT)) show promise as adding to the options available in the future, but are not immune to the same priniples and limitations that apply to all investigations. CORONARY ANGIOGRAPHY IN THE INVESTIGATION AND MANAGEMENT OF CHEST PAIN With its urrently unrivalled ability to demonstrate oronary anatomy and as a prelude to revasularisation, oronary angiography has a pivotal role in the assessment of a patient s CHD. While the gold standard for anatomy, it does not however provide funtional information and arries a small but definite mortality (1 in 1400). Generally there has been under-provision of angiography in the UK and this has skewed servies for the assessment of hest pain by reating the need for rationing by referral or waiting times. There are many guidelines desribing indiations for angiography and inreasingly UK, European, and US indiations are oalesing. 20 De Bono and olleagues 21 desribe a prioritisation system based on severity of angina, exerise test outome, age, and risk fators that produed a sore whih orrelated with the finding of three vessel disease (inluding proximal left anterior desending artery) or left main stem disease (fig 3). More detailed inspetion of the soring system shows that in essene lass 3 angina or a positive exerise test in stages 1 or 2 (Brue protool) give a reasonable likelihood of signifiant disease. These are Amerian Heart Assoiation/Amerian College of Cardiology (AHA/ACC) lass 1 and 2a indiations for angiography, suggesting that simply following these guidelines suffies. The ACRE study investigated the issue of appropriateness of angiography referrals. 22 An expert panel established a onsensus on appropriateness aross a range of indiations. These were then prospetively applied to a ohort of 3631 patients undergoing angiography and mathed to the Table 3 The NICE guidane on myoardial perfusion sintigraphy (MPS) 1.1 MPS using single photon emission omputed tomography (SPECT) is reommended for the diagnosis of suspeted oronary artery disease (CAD) in the following irumstanes: As the initial diagnosti tool for people with suspeted CAD for whom stress eletroardiography poses partiular problems of poor sensitivity or diffiulties in interpretation, inluding women, patients with ardia ondution defets (for example, left bundle branh blok), and people with diabetes, and for people for whom treadmill exerise is diffiult or impossible As part of an investigational strategy for the diagnosis of suspeted CAD in people with lower likelihood of CAD and of future ardia events. The likelihood of CAD will be based on the assessment of a number of risk fators inluding age, gender, ethni group, family history, assoiated o-morbidities, linial presentation, physial examination, and results from other investigations (for example, blood holesterol values or resting ECG) 1.2 MPS using SPECT is reommended as part of the investigational strategy in the management of established CAD in people who remain symptomati following myoardial infartion or reperfusion interventions Figure 3 Reeiver operating harateristi (ROC) urve for the ability of a soring system to identify patients with three vessel (inluding proximal left anterior desending artery) or left main stem disease. Reprodued with permission from De Bono and olleagues. 21 angiographi findings. Sixty two per ent of referrals were rated appropriate, 5% inappropriate, and 33% unertain appropriateness. Mortality and revasularisation rates orrelated strongly with appropriateness although 11% of the inappropriate angiograms revealed three vessel or left main stem disease. Interestingly, when urgeny was analysed, the median waiting time for appropriate patients was 91 days but just 58 days for inappropriate patients. REST PAIN AND ACUTE CORONARY SYNDROMES There are several important differenes in the assessment of suspeted ishaemi rest pain ompared to exertional angina that reate diagnosti and logistial hallenges. One of the most valuable features of the history, namely the exertional nature of ishaemi hest pain, by definition annot be invoked. The diagnosti proess therefore relies on using a ombination of the pre-test probability of CHD with other features of the history, the examination (still generally non-ontributory), and the resting ECG. The resting ECG is of more value ompared to when assessing suspeted exertional angina beause, partiularly if the patient has symptoms Heart: first published as /hrt on 16 Deember Downloaded from on 16 Otober 2018 by guest. Proteted by opyright.

5 Table 4 Comparison of hest pain assessment units (CPAUs) and rapid aess hest pain linis (RACPCs) CPAU during the reording, it has some parallels with the usefulness of the ECG during ishaemia provoking exerise. The essential role of risk stratifiation, together with the management of patients with suspeted aute oronary syndromes (ACS), is evidene based and desribed in guidelines. 23 Currently the majority of these patients are assessed within emergeny departments. The introdution of readily available assays for troponin (I and T) has ontributed signifiantly to the risk stratifiation of suspeted ACS. 24 However, the sensitivity of the result is established for assay 12 hours after onset of symptoms, so not neessarily on arrival in the emergeny department. The speifiity depends on the pretest probability of disease, and inappropriate measurement of troponin in very low risk patients leads to false positive results. Undetetable or low onentrations of troponin are a strong but not omplete preditor of low short term event rates. They do not exlude CHD and loal algorithms must show that they enable early ambulation and stress testing, not immediate disharge without follow up. Business ases for introduing troponin assays rely on ost effetiveness data partiularly foused on lengths of stay. False positives leading to unneessary admissions, failure to provide results promptly, and failure to provide same day stress testing after the result is available, will eradiate ost savings. As an alternative servie model the introdution of hest pain assessment units (CPAUs) has been advoated. 25 These dediated areas inorporate a monitoring area for observing patients with suspeted ACS until an appropriately timed troponin assay an be performed, and stress testing failities to determine diagnosis, short term risk, and initiate treatment. Potentially blurred but important differenes exist between CPAUs and RACPCs (table 4). In establishing models for hest pain assessment within a hospital these must be appreiated when onfiguring servies. Randomised trials, initially from North Ameria but now in the UK, support the introdution of CPAUs. 26 The CHEER study from New York showed ost savings and equivalent safety omparing a CPAU with usual are. A reent randomised trial in Sheffield of 972 patients showed redued admissions and ost savings without ompromising safety for a CPAU ompared to usual are. 27 A hybrid approah, rather than segregating aute hest pain patients, is to invest in eduating staff and emergeny department teams and apply lear simple algorithms or integrated are pathways to their are. The ROMEO study in Bath showed the effetiveness of this approah. 28 In this study a rapid protool for ruling out myoardial ishaemia, RACPC Open times Round the lok Working hours Monitoring equipment Definitely Resusitation trolley only Beds Definitely Examination ouh only Troponin assays Definitely Seletively useful Length of stay 12 hours 1 2 hours Loation Typially near emergeny department Typially near ardiology department Staffing Speialist nurse (thrombolysis) and liniian Various, inluding nurse speialist/ tehniian Patients Rest pain some at high risk of aute haemodynami deterioration Mainly low to moderate risk during assessment involving troponin assay followed by exerise testing, was used to ahieve median admission times of 23 hours for patients presenting with suspeted ACS without adverse events among disharged patients. NON-CARDIAC CHEST PAIN The hallenge of non-ardia hest pain and its utilisation of ardiologist s time and resoure are substantial. Over two thirds of patients assessed in RACPCs do not have a ardia ause to their symptoms. While perhaps ounter intuitive to a ardiologist, areful investment of time in arranging the assessment, diagnosis, and management of non-ardia hest pain is worthwhile if the servies for those with ardia disease are not to be ompromised. Prompt rather than delayed reassurane seems more effetive, partiularly ompared to a prolonged period of suspeted CHD. 29 RACPCs may well have an important role here. RACPCs an quikly establish a diagnosis, not exerise low risk patients, provide leaflets and brief explanation, and, if using a database, make entering patients with non-ardia disease easy and rapid through appropriate default settings. At all times one should ommuniate fully with patients so they understand where there is unertainty for example, when treatment is a trial and an therefore be safely stopped at a later stage if signifiant disease is exluded (table 5). When is investigation appropriate to reassure the patient? As has been repeatedly disussed most of our tests Table 5 Priorities in addressing non-ardia hest pain. Adapted from Bass and Mayou 29 General Diagnose promptly and positively Consider oesophageal/musuloskeletal/hyperventilation/ psyhologial Avoid over investigation and referral Provide speifi treatments as appropriate For others (no speifi treatment available) Explain diagnosis and reassure that this is a real and ommon problem Advise to not avoid exerise Disuss onerns Provide written information Involve relatives Consider follow up appointments, espeially after prolonged investigation Consider ognitive behaviour therapy/antidepressant drugs/ psyhologial intervention 109 Heart: first published as /hrt on 16 Deember Downloaded from on 16 Otober 2018 by guest. Proteted by opyright.

6 110 Investigation and management of hest pain: key points Most patients presenting in primary and seondary are with hest pain do not have oronary heart disease (CHD) as the ause The value of all tests and investigations depends on the quality of the test and the pre-test probability of disease A onsistent and omprehensive, not omplex, assessment using history and appropriately performed and interpreted non-invasive tests will ahieve a orret diagnosis in most ases An effetive pathway for the investigation of hest pain needs to lead to diagnosis, risk stratifiation, and prompt initiation of treatment Managing non-ardia hest pain effetively releases time and resoures for those with CHD establish a probability of disease. In reality non-invasive tests struggle to distinguish a low risk of the presene of CHD, from the presene of CHD but at very low risk of events, an unertainty that an be unomfortable for patients and their dotors. An example is a patient with exertional pain reprodued on a treadmill but not assoiated with ECG hanges. Keavney and olleagues 30 looked at the ost of aring for 69 onseutive patients in the 12 months before and after a normal oronary angiogram. They showed that the ost of the angiogram would be reouped in 18 months. So at least by this marker, a normal oronary angiogram was of use. De Fillipi and olleagues 31 randomised 248 patients with a low risk of ardia events after CPAU assessment to exerise testing and angiography if abnormal, or angiography for all, before disharge. Angiography for all led to 12 extra revasularisations, but redued re-attendanes and admissions. However, no infarts ourred in those with normal exerise tests during the one year follow up. 31 CONCLUSIONS Braunwald s textbook omments that the diagnosis of ardia amyloidosis is diffiult and historially was often made post-mortem. 32 This should not be the ase with CHD. The great majority of patients first present alive and an be diagnosed with a foused history and a stepwise programme of appropriately requested, performed, and interpreted investigation. The elements of this pathway an be performed in any distrit general hospital and muh of it undertaken by appropriately trained nursing and non-onsultant grade staff. It is a entral role of the ardiologist to oordinate teams to provide an assessment servie for those presenting with suspeted ardia hest pain. Cardiologists ultimately will have substantial responsibility for telling patients whether they have CHD and its severity. Suffiient evidene exists to suggest that if we follow a onsistent, arefully designed, integrated, audited, and oordinated pathway of assessment, the vast majority of the time we will get it right. REFERENCES 1 Stewart S, Murphy N, Walker A, et al. The urrent ost of angina petoris to the National Health Servie in the UK. Heart 2003;89: Nilsson S, Sheike M, Engblom D, et al. 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