Questions and answers on workup diagnosis and risk stratification: a companion document of the 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

Abstract

Q1. You are on rounds in the emergency department and your intern asks you: what is the main difference between non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina? NSTEMI is characterized by ischaemic symptoms associated with acute cardiomyocyte injury (=rise and/or fall in cardiac troponin T/I), while ischaemic symptoms at rest (or minimal effort) in the absence of acute cardiomyocyte injury define unstable angina. This translates into an increased risk of death in NSTEMI patients, while unstable angina patients are at relatively low short-term risk of death (sections 3.3.1 and 3.3.2, Figure 1). Q2. A 72-year-old patient with hypertension and hypercholesterolaemia as cardiovascular risk factors (CVRF) presents to the emergency department with typical chest pain of 3 h duration, palpitations, atrial fibrillation with a ventricular rate of about 120 beats per minute, ST depression on electrocardiogram (ECG), and a mild elevation in cardiac troponin (cTn) (twice the upper limit of normal [ULN]). Is it correct to state that the underlying process is a rupture, ulceration, fissuring, or erosion of a coronary atherosclerotic plaque? No. According to the universal definition of myocardial infarction (MI), two main subtypes of NSTEMI have to be differentiated: type 1 MI, characterized by any of the processes just previously described, and type 2 MI, in which an extra-coronary condition is the main cause of imbalance between myocardial oxygen supply and demand (e.g. tachycardia, anaemia, hypertension, or hypotension). The patient described may have had both (sections 3.3.1 and 3.3.2, Figure 1). Q3. Which are the three mandatory diagnostic cornerstones of the early diagnosis of non-ST-elevation acute coronary syndrome (NSTEMI) among the following: past clinical history including a detailed description of the chest pain characteristics, 12-lead ECG, chest X-ray, elevated and dynamic rise in cTn, treadmill test, computed tomography (CT) angiography, and myocardial perfusion scan? Early diagnosis of NSTEMI relies on clinical assessment (i.e. past clinical history including a detailed description of the chest pain characteristics), 12-lead ECG, and cTn (sections 3.3 and 3.3.2, Figure 1). Q4. You are challenged by a new cardiology fellow regarding the cTn assay used in your institution. She states that current ESC guidelines recommend using a high-sensitivity cTn (hs-cTn) assay and that your current assay is not high-sensitivity. What are the advantages of hs-cTn? Hs-cTn measurements are recommended over less sensitive ones, as they provide higher diagnostic accuracy at identical low cost. The higher diagnostic accuracy mainly translates into the possibility for earlier and safer rule-out of MI, and therefore shorter length of stay in the emergency department and lower treatment cost (which are mainly determined by the time in the emergency department) (section 3.3.2, Figure 2). Q5. You plan to introduce the measurement of hs-cTn in your hospital. A fellow asks: what will the impact be on the diagnosis of NSTEMI and unstable angina in patients presenting to the emergency department with acute chest pain? With the introduction of hs-cTn there will be some increase in the prevalence of NSTEMI and a reciprocal decrease in the incidence of unstable angina. The percentage of reclassified patients depends on the difference in sensitivity between the current and the new assay. If the current assay has low sensitivity and is a ‘conventional’ cTn assay, an increase in NSTEMI diagnoses is to be expected by approximately 4% absolute and 20% relative, with a corresponding decrease in unstable angina. If the current assay is already a sensitive cTn assay, then the percentage of reclassified patients will be smaller (e.g. 1–2% absolute, 5–10% relative) (section 3.3.2, Figure 2). Q6. You are called by a fellow from the emergency department regarding an 85-year-old patient presenting with a hip fracture following a fall. For unknown reasons, cTn has been measured and the concentration is twice the upper limit of normal. The 12-lead ECG is normal. He said that the elevated cTn allows him to diagnose NSTEMI and asks for the need for early invasive coronary angiography. It is very unlikely that NSTEMI is the correct diagnosis in this patient. Accordingly, there is no need for early invasive coronary angiography. A mild and probable constant and chronic cTn elevation is common in the elderly patient and a reflection of the pre-existing cardiac disease (known or unknown to the patient), resulting in chronic cardiomyocyte injury (section 3.3.2, Figure 2). Q7. A 50-year-old patient with no relevant past medical history presents with persistent severe retrosternal chest pain radiating to both shoulders and arms which started 4 h earlier. Haemodynamic status is stable and the initial physical examination is unremarkable. The 12-lead ECG is normal. The initial hs-cTn T concentration is 300 ng/L (ULN < 14 ng/L). Is it possible to make a clear working diagnosis or do you need a second hs-cTn measurement? There is no need for a second troponin assessment. The diagnosis of NSTEMI is made and appropriate treatment should be initiated. The positive predictive value for NSTEMI in patients with typical symptoms and a substantial (> 20 times the 99th percentile) elevation in cTn is > 90% (section 3.3.3). If the institution uses the ESC hs-cTn T 0h/1 h-algorithm, an initial hs-cTn T concentration above 52 ng/L allows triage of patients towards rule-in (section 3.3.3, Figure 3, Table 5). The next four scenarii highlight how to use the available different types of hs-cTn. Q8. A 60-year-old patient without prior history of coronary artery disease (CAD) presents to the emergency department with recurrent right-sided thoracic chest pain. The last chest pain episode started 5 h prior to hospital admission and is still ongoing. He is haemodynamically stable and the physical examination is normal. The 12-lead ECG is also normal. The initial hs-cTn T level is normal at 4 ng/L (ULN < 14 ng/L). The intern in the emergency department asks you as a cardiology consultant if this single very low hs-cTn T concentration allows the rule-out of NSTEMI. Yes. As the patient presented more than 3 h after chest pain onset, the single measurement rule-out pathway of the ESC hs-cTn T 0h/1 h-algorithm can be applied, which allows the rapid and safe triage towards rule-out of NSTEMI if the hs-cTn T concentration is < 5 ng/L. The negative predictive value for the rapid rule-out of NSTEMI in this setting is > 99.5%. Most of these patients are also excellent candidates for rapid discharge and outpatient management, possibly including non-invasive stress testing (preferably with imaging) (section 3.3.3, Figure 3, Table 5). Q9. A 60-year-old patient without prior history of CAD presents to the emergency department with recurrent right-sided thoracic chest pain. The last chest pain episode started 5 h prior to hospital admission and is still ongoing. He is haemodynamically stable and the physical examination is normal. The 12-lead ECG is also normal. The initial hs-cTn I (Architect) level is normal at 2 ng/L (ULN < 26 ng/L). The intern in the emergency department asks you as a cardiology consultant if this single very low hs-cTn I Architect concentration allows the rule-out of NSTEMI. Yes. As the patient presented more than 3 h after chest pain onset, the single measurement rule-out pathway of the ESC hs-cTn I Architect 0 h/1 h-algorithm can be applied, which allows the rapid and safe triage towards rule-out of NSTEMI if the hs-cTn I concentration is < 4 ng/L. The negative predictive value for the rapid rule-out of NSTEMI in this setting is > 99.5%. Most of these patients are also excellent candidates for rapid discharge and outpatient management, possibly including non-invasive stress testing (preferably with imaging) (section 3.3.3, Figure 3, Table 5). Q10. A 60-year-old patient without prior history of CAD presents to the emergency department with recurrent right-sided thoracic chest pain. The last chest pain episode started 5 h prior to hospital admission and is still ongoing. He is haemodynamically stable and the physical examination is normal. The 12-lead ECG is also normal. The initial hs-cTn I Centaur level is normal at 2 ng/L (ULN < 47 ng/L). The intern in the emergency department asks you as a cardiology consultant if this single very low hs-cTn I Centaur concentration allows the rule-out of NSTEMI. Yes. As the patient presented more than 3 h after chest pain onset, the single measurement rule-out pathway of the ESC hs-cTn I Centaur 0 h/1 h-algorithm can be applied, which allows the rapid and safe triage towards rule-out of NSTEMI if the hs-cTn I Centaur concentration is < 3 ng/L. The negative predictive value for the rapid rule-out of NSTEMI in this setting is > 99.5%. Most of these patients are also excellent candidates for rapid discharge and outpatient management, possibly including non-invasive stress testing (preferably with imaging) (section 3.3.3, Figure 3, Table 5). Q11. A 60-year-old patient without prior history of CAD presents to the emergency department with recurrent right-sided thoracic chest pain. The last chest pain episode started 5 h prior to hospital admission and is still ongoing. He is haemodynamically stable and the physical examination is normal. The 12-lead ECG is also normal. The initial hs-cTn I Access level is normal at 3 ng/L (ULN < 18 ng/L). The intern in the emergency department asks you as a cardiology consultant if this single very low hs-cTn I Access concentration allows the rule-out of NSTEMI. Yes. As the patient presented more than 3 h after chest pain onset, the single measurement rule-out pathway of the ESC hs-cTn I Access 0 h/1 h-algorithm can be applied, which allows the rapid and safe triage towards rule-out of NSTEMI if the hs-cTn I Access concentration is < 4 ng/L. The negative predictive value for the rapid rule-out of NSTEMI in this setting is > 99.5%. Most of these patients are also excellent candidates for rapid discharge and outpatient management, possibly including non-invasive stress testing (preferably with imaging) (section 3.3.3, Figures 3 and 4, Table 5). Q12. A 60-year-old patient without prior history of CAD presents to the emergency department with recurrent right-sided thoracic chest pain. The last chest pain episode started 5 h prior to hospital admission and is still ongoing. He is haemodynamically stable and the physical examination is normal. The 12-lead ECG is also normal. The initial hs-cTn I Vitros level is normal at 0.7 ng/L (ULN < 11 ng/L). The intern in the emergency department asks you as a cardiology consultant if this single very low hs-cTn I Vitros concentration allows the rule-out of NSTEMI. Yes. As the patient presented more than 3 h after chest pain onset, the single measurement rule-out pathway of the ESC hs-cTn I Vitros 0 h/1 h-algorithm can be applied, which allows the rapid and safe triage towards rule-out of NSTEMI if the hs-cTn I Vitros concentration is < 1 ng/L. The negative predictive value for the rapid rule-out of NSTEMI in this setting is > 99.5%. Most of these patients are also excellent candidates for rapid discharge and outpatient management, possibly including non-invasive stress testing (preferably with imaging) (section 3.3.3, Figure 3, Table 5). Q13. A 60-year-old patient without prior history of CAD presents to the emergency department with intermittent recurrent moderate right-sided thoracic chest pain without radiation over the last 2 days. The last chest pain episode started 2 h prior to hospital admission and lasted for 30 min. He is haemodynamically stable and the physical examination is normal. The 12-lead ECG is also normal. The initial hs-cTn T level is normal at 4 ng/L (ULN <14 ng/L). The intern in the emergency department asks you as a cardiology consultant if the patient can be discharged. No. As the patient presented very early after chest pain onset, the intern needs to wait for the second cTn measurement at 1 h if using the ESC hs-cTn T 0 h/1 h-algorithm or at 2 h if using the ESC hs-cTn T 0 h/2 h-algorithm. If the second measurement is also within normal limits and there is NO relevant change to the measurement at presentation, NSTEMI can be reliably ruled-out and the patient is to be considered at low risk of cardiac events. From a cardiology may then be If no clear for chest pain or is to the may non-invasive stress testing (preferably with imaging) on an outpatient (section 3.3.3, Table Figure A 60-year-old patient with a history of CAD presents to the emergency department with chest pain and for 2 days. The right-sided thoracic chest pain is moderate in and in The last episode of chest pain started h prior to admission and the patient is still in the emergency He is haemodynamically stable and the physical examination is unremarkable. The 12-lead ECG in I and which already in the ECG last The initial hs-cTn I Architect concentration is very at 2 ng/L (ULN < 26 ng/L). The emergency department a to a you by that is that the chest pain not acute and no or in this are Is Yes. on the between and test, can be reliably ruled-out with a single very low level of hs-cTn unstable angina is unlikely is expected to to some of cTn diagnosis as should be considered (section 3.3.3, 4 and Figure You are the emergency pain and an patient with a history of prior MI, and disease presenting with persistent moderate right-sided thoracic chest pain for h that in and has mild and an over the last 3 days. He is haemodynamically stable and the initial physical examination over the of the ECG in which already on the ECG 3 A chest an in the of intern is about to and in the and the hs-cTn T level is from the as intern asks you if the patient needs treatment for or This patient has a for and a low for NSTEMI. the has you need to the value of hs-cTn at as as the after 1 h or 2 If the hs-cTn are elevated (e.g. to the assay 18 ng/L if is 14 then the mild elevation in hs-cTn in this patient can be to cardiac than NSTEMI (e.g. pre-existing or disease some of cardiomyocyte injury to and no treatment is A rise or fall in hs-cTn is for the diagnosis of and have higher h after the of acute chest pain (section 3.3.3, Figures 3 and 4, 4 and 5). You are the cardiology consultant for the of in the emergency patient a asks you the of patients presenting with acute chest pain to the emergency department to reliably rule-out or rule-in acute No. a hs-cTn 0 h 1 h-algorithm or a hs-cTn h-algorithm, the of patients can be reliably ruled-out or within the in the emergency department (sections and 3.3.3). the of patients (> can be after rapid rule-out of and as using these (section 3.3.3, Figure 3, Table 5). You are the emergency A you regarding the of a 60-year-old with a history of CAD presenting with moderate thoracic chest pain without radiation that started 2 h prior to admission and in the emergency She is haemodynamically stable and the physical examination and 12-lead ECG are unremarkable. of hs-cTn T at and 1 h normal and identical at ng/L (ULN < 14 ng/L). NSTEMI be the negative predictive value for in patients as by the hs-cTn T 0 h/1 h-algorithm is in with clinical assessment and the 12-lead ECG as mandatory of the 0 h/1 h-algorithm allows the early rule-out of and early of patients that are candidates for outpatient (i.e. no or non-invasive It is to highlight that prior to of acute chest as and need to be considered (section 3.3.3, Figures 3 and 4, 4 and 5). You are the emergency A asks you about the of a without and without CAD presenting with moderate retrosternal chest pain without radiation that started 3 h prior to admission and lasted for 1 She is haemodynamically pain and the physical examination as as the 12-lead ECG are normal. of hs-cTn I Architect at are ng/L (ULN < 26 ng/L). intern is using the ESC 0 h/1 h-algorithm you just in the hospital and you that to the the patient can be the intern to what it the patient have The positive predictive value for in patients as by the hs-cTn T 0 h/1 h-algorithm is in with clinical assessment and the 12-lead ECG mandatory of the 0 h/1 h-algorithm allows the early of patients are candidates for early invasive coronary angiography, as of the rule-in patients with a diagnosis than acute will have that also coronary for including and unstable angina. This patient should early invasive coronary (section 3.3.3, Figure 3, Table The measurement of hs-cTn is mandatory in patients presenting with Is it to cardiovascular in to hs-cTn If which It is to cardiovascular in to hs-cTn (section from the emergency asks you if to the of a patient with acute chest pain for the early rule-out of The value of depends on the sensitivity of the cTn assay If using a cTn assay with provide diagnostic value and is as an for the rapid rule-out of within a if as recommended in the ESC a hs-cTn assay within a hs-cTn 0 h/1 h-algorithm or hs-cTn 0 h/2 h-algorithm, not have value and should not be used (section fellow asks you if may in the diagnosis of patients with not in the it for death and/or the of in patients with (section A has been in the emergency asks you if can use of the ESC hs-cTn 0 h/1 for of NSTEMI in patients presenting with acute chest pain. Most this is not The new ESC hs-cTn 0 h/1 for of NSTEMI in patients presenting with acute chest pain can be used with hs-cTn the of current do have sensitivity and be used for rapid there is and are in (section A with a past medical history of thoracic for and on 1 is to the emergency department for acute retrosternal chest pain with radiation to the She in pain The physical examination is normal. The 12-lead ECG 3 depression in and The emergency department asks you the patient should coronary or has to wait for the of the cTn which are expected to from the in about the very of myocardial and the myocardial at the patient should invasive coronary (section Figure You are working in the emergency department on at A new patient with angina at minimal which started 3 The ECG on admission a and no The normal for hs-cTn at and 1 h as as a level of The patient is haemodynamically stable rate beats per has in the of both (i.e. are not states that you can the patient to the and him on invasive coronary for Is No. You should the of risk of two that patients with a risk for to the risk by (i.e. > for the risk and for the risk may do with an early invasive as to a invasive The risk is for this patient. to guidelines an invasive coronary within h should be and you should the patient for h from (section Figure patient the emergency department chest pain at rest for earlier in the The patient is haemodynamically has no and no elevation is The hs-cTn level is 52 and ng/L (ULN 14 at and 1 h 0 h/1 h-algorithm rule-in about the risk that is on the following rate level no no cardiac states that the for the on can be the patient can wait risk not above Is correct this No. The hs-cTn T level is elevated with a rise with This is a of the risk the patient should also invasive coronary within h (i.e. and not risk is recommended of the and ischaemic risk can be and using the risk assessment by of the risk has over assessment by the (section Figure your on ischaemic risk your then asks you have been regarding the risk for there are also risk clinical is challenged by the between and ischaemic risk factors and the accuracy of the risk these risk (e.g. may still be to and patients (section A with a history of is to the emergency department of acute chest pain with radiation to shoulders and This by and which lasted for 30 after 4 h medical the patient pain and the physical examination unremarkable. The 12-lead ECG no ST and/or T The initial as as the 1 h level of hs-cTn is the without a dynamic The risk is The emergency department asks the cardiology fellow on an invasive or non-invasive coronary assessment should on patient and characteristics, as as setting and The patient to the with a risk of of < risk of death to following the a non-invasive assessment is testing by stress or cardiac or by coronary (sections and Figures 3 and 4, Table The emergency department to to fellow to this is in with current with is of the recommended in this should be considered to CAD in haemodynamically stable patients with acute chest pain of with initial negative without ischaemic ECG and low (section This of invasive coronary A presents with of a on the and for 3 a of intermittent chest over the last both at rest and She has a positive history for The initial ECG atrial fibrillation with a rate of and then with no ischaemic after 30 of a and 1 h hs-cTn 30 ng/L and ng/L (ULN 14 A asks as of the emergency should be to rule-out coronary artery has a diagnostic accuracy for and may be is elevated of hs-cTn may be to myocardial injury to rapid ventricular rate a is recommended of the chest the last and the positive history for CAD (section Figures 3 and A the of patients with acute chest pain by the following: with clinical cTn and ECG in patients with the need Is this at of non-invasive in of among risk patients, has been to increase testing and without clinical for the patient. the in radiation in of with low radiation as as appropriate of is not available on a at institution (section 3.3 and Figures 3 and You are on as a in the emergency department and you a 50-year-old with new acute chest pain without for 3 She is for hypertension, and The 12-lead ECG and measurements of hs-cTn 0 h/1 h are the ng/L). The states that this patient very has unstable angina and should therefore early invasive coronary angiography. Is No. There is no of severe or myocardial early invasive coronary is not This patient may have unstable also of acute chest pain. is to this patient has CAD (sections 3.3 and Figure 3, Figure A with no prior relevant medical is to the emergency department of a typical chest pain > are normal for that is The ECG ST depression in the and ventricular The hs-cTn I is ng/L (ULN <14 ng/L). She and a invasive coronary which no that the is and the patient with Is No. is a working diagnosis assessment possible for cTn may be coronary or is in this should be to or for the cTn may not be the correct will to the diagnosis (section Figure Table A with hypertension and presents to the emergency department of recurrent of chest not associated with for a physical examination is unremarkable. and second hs-cTn I are both within normal and the ECG is normal. the patient has a of chest pain with elevation of in and invasive coronary is and a mild disease on the coronary artery and artery is The fellow you that there is an available for in 30 you do invasive while for the history and symptoms that coronary may be the while for to be may be with or tomography may also be for the of or coronary artery (section Figure Table fellow is the discharge of a for recurrent chest positive hs-cTn I value of and normal not any some stable and not She is not to any after you No. with a diagnosis of of unknown cause may be to guidelines for atherosclerotic with and is recommended and and is may be considered (section Figure Table A to your outpatient for a two after a for recurrent chest pain with elevated mild of the and invasive coronary is normal. He is with the of and is for 2 What is your This patient without a diagnostic NSTEMI to be the probable cause of to possible and syndrome should have been earlier to the correct It be to as as possible (section Figure Table A is to the emergency department for chest pain associated with and a earlier. The ECG and no The hs-cTn is ng/L (ULN 14 and a normal ventricular and a coronary the following is normal. of chest pain with of atrial fibrillation this should be as an NSTEMI you It is probable that symptoms and myocardial injury are to the of It is recommended to patients with an initial diagnosis of and a underlying cause to the This patient should be to the atrial fibrillation ESC with on risk assessment and of atrial fibrillation (section Figure Table you diagnose and a patient for that in an is not is of the diagnostic in the diagnostic for diagnosis of or also and the are negative and is not patients should to ventricular myocardial which may to the underlying If is still considered the probable the patient should be to the If the diagnosis is of the treatment should the guidelines for atherosclerotic disease (section Figure Table A of with no prior relevant medical at the emergency department after chest pain while She still has some chest the physical the ECG a 1 ST depression in the and there is mild of the at and 2 h hs-cTn I are ng/L and ng/L (ULN 14 She and and is to the coronary some with a of the with coronary this patient with coronary and Is According to the available from very patients, a should be the in type I with no coronary and coronary medical treatment is still hypertension is an of recurrent should be considered and should be the in this of The of among these patients is still patients, invasive coronary or may be considered as in to clinical (section Figure The of in the of this is available on the ESC The are available and The of these of has been for and use use is of the ESC may be or in any without from the can be of a to the of the and the to on of the ESC The ESC the of the ESC and after of the and medical and the available at the time of The ESC is not in the of any and/or between the ESC and any or guidelines by the relevant in in to use of or are to the ESC into clinical as as in the and the of diagnostic or medical the ESC do not in any the of to make appropriate and in of condition and in with that patient appropriate and/or the do the ESC from into and the relevant or guidelines by the in to in of the to and It is also the to the and to and medical at the time of

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