Identifying patients with acute total coronary occlusion in NSTEACS: finding the high-risk needle in the haystack

This editorial refers to ‘Impact of total occlusion of culprit artery in acute non-ST elevation myocardial infarction: a systematic review and meta-analysis’†, by A.R. Khan et al., on page 3082. Acute coronary occlusion leads, when prolonged, to irreversible myocardial necrosis. Seminal pre-clinical studies showed that the extent of infarction is related to the duration of coronary occlusion.1 On the basis of these and other studies, it was proposed that recanalization of an occluded artery could lead to myocardial reperfusion and salvage, reduction of myocardial infarct size, preservation of left ventricular function, and improved clinical outcomes.2–5 Comprehensive and timely identification of the full spectrum of patients presenting with suspected acute coronary syndrome (ACS) who have acutely occluded coronary arteries remains a major clinical challenge. In routine clinical practice, the 12-lead surface electrocardiogram (ECG) performed at the time of first medical contact is the principal determinant of immediate management of patients presenting with a suspected ACS. The ECG is a simple, cheap, and ubiquitously available bedside test. ST-segment elevation in two or more leads and new or presumed onset left bundle branch block (LBBB) are known ECG features of epicardial coronary occlusion and, if present, identify a group of patients who are considered eligible for immediate reperfusion, preferably by primary percutaneous coronary intervention,6 provided they are <12 h from symptom onset. Timely reperfusion has contributed substantially to improved clinical outcomes in the ST elevation ACS population.7–9 Current guidelines do not recommend routine emergent angiography and revascularization for the large (and growing) subset of patients with suspected ACS but without persistent ST elevation (non-ST elevation, NSTEACS) at presentation.10 This is due to the fact that the absence of ST-segment elevation is interpreted to indicate lack of total coronary occlusion and therefore not to warrant emergency myocardial reperfusion. Angiographic series have demonstrated that NSTEACS patients generally have critical complex coronary stenoses, with only a minority having total occlusion of the culprit artery. In addition, there is ample documentation of the dynamic fluctuations in coronary artery patency and attendant ST changes in ACS patients.11 NSTEACS patients initially undergo risk stratification based on age, troponin elevation, ECG changes, haemodynamic status, and co-morbidity. These factors are incorporated into validated risk calculators, such as the GRACE tool, which can be used to determine the treatment pathway, including choice of guideline-directed medical therapy and referral for an early invasive strategy which should be immediate (<2 h) in patients at very high risk [defined as haemodynamic instability or cardiogenic shock, recurrent or ongoing chest pain refractory to medical treatment, life-threatening arrhythmias or cardiac arrest, mechanical complications of myocardial infarction (MI), acute heart failure, or recurrent dynamic ST–T wave changes] and early (within 24 h of presentation) in patients at high risk,10 which is typically defined as any of the following three criteria (GRACE risk score >140, dynamic ST–T wave changes whether symptomatic or silent, and rise or fall of troponin compatible with MI). The incidence of NSTEACS is rising12 , 13 and, despite contemporary management, there remains considerable unmet clinical need to reduce adverse cardiovascular events in this patient population, which have not diminished to the same degree as in STEACS patients.14 This will rely on improved identification of the high-risk patients who may benefit from expedited angiography and revascularization. A subgroup falling into this category is the substantial number of patients with suspected NSTEACS who have acutely occluded arteries. In the current issue of the journal, Khan et al.15 evaluate the prognostic significance of acute total occlusion (TO) of the culprit artery. From a systematic review of the literature, the authors identified seven contemporary studies for meta-analysis, which comprised four registries, two post-hoc analyses of randomized controlled trials, and one prospective cohort study. The authors have performed a careful analysis, though they acknowledge that the overall quality of the source evidence was low and they were unable to control for publication bias. The aggregate study population consisted of 40 777 patients with a presumed first NSTEACS in whom the rates of death and major adverse cardiac events (MACE) were ascertained in the short (<30 days) and medium to long term (6–12 months). Patients were categorized as having TO (25%) or not (75%). Coronary angiography was performed on average ∼3 h earlier in the TO group (31.3 vs. 34.2 h), with little difference in the time to angiography in both groups. In six studies, coronary angiography was used to define the culprit artery, three of which also utilized ECG and echo data to aid identification of the culprit artery. In the remaining study, the culprit artery was defined as the first artery to be treated percutaneously. The limitations of using the coronary angiogram alone to identify the culprit artery are well known.16 Independent validation of the culprit artery was performed in only two studies. The presence or absence of collateral flow and description of TO morphology on angiography were not systematically reported in the analysed studies, so the possibility of inclusion of chronic coronary artery occlusions cannot be excluded with certainty. The major finding of the current study is that, compared with patients without TO, the presence of TO was associated with an increased risk of MACE and all-cause mortality in both the short and medium to long term. The magnitude of the increased mortality risk was striking: 65% in the short term and 39% in the long term. TO was more commonly observed in the right coronary (40%) and circumflex (32%) coronary arteries, similar to previous observations in the ACC-NCDR registry,17 and was associated with ST depression, T wave inversion, and pathological Q waves on the presenting ECG. The rate of Killip class III/IV was not increased, though left ventricular ejection fraction was ∼2% lower in patients with TO. Qualitative analyses suggested increased levels of cardiac biomarkers in TO patients. These findings indicate that TO constitute a high-risk subset of NSTEACS patients. The findings of the current study are consistent with previous reports which have suggested that this group of patients are at particular risk of developing irreversible myocardial injury and greater left ventricular dysfunction as a result of delayed angiography and revascularization.18 Of note, in the analysis by Khan et al., the mean time to angiography and revascularization in patients both with and without TO was greater than the 24 h window recommended for high-risk patients in current guidelines.12 Despite similar high rates of successful revascularization, clinical outcomes remained worse in patients with TO. Whether these patients would benefit from urgent invasive management remains to be proven but would seem a reasonable hypothesis to test, provided these patients can be identified rapidly in the acute setting. This is where the main problem lies. If clinical management is to be altered (with management according to a STEMI-like pathway, with emergent angiography and reperfusion) in order to improve the outcome of these patients with suspected TO, they need to be identified. Yet, today, there does not seem to be a simple clinical or ECG algorithm to allow this in real time. Many of the challenges are related to the limited sensitivity and specificity of the ECG to identify acute coronary occlusion in the various epicardial coronary artery distributions. Clinicians need to be alert to the spectrum of 12-lead surface ECG changes (Figure 1), other than classical ST-segment elevation, that can accompany acute occlusion of the coronary arteries. For instance, ST-segment elevation in lead aVR is evocative of diffuse triple vessel disease or left main stenosis or occlusion;19 , 20 pre-cordial ST segment depression at the J point followed by peak positive T waves (the ‘De Winter pattern’) is highly evocative of occlusion of the left anterior descending (LAD) coronary artery; deeply inverted or biphasic T waves in the pre-cordial leads V2–V3 are evocative of a critical LAD stenosis (Wellens’ sign);21 , 22 ST depression in right pre-cordial leads V1–V3 should lead to recording of posterior leads V7, V8, and V9 in order to avoid missing true posterior STEMI related to occlusion of the left circumflex;23 , 24 and ST elevation in right pre-cordial leads V3R or V4R is evocative of proximal occlusion of the right coronary artery with right ventricular infarction.25 The diagnosis of acute coronary occlusion using the surface 12-lead ECG is also challenging in patients with known LBBB,26 , 27 with a ventricular paced rhythm or with left ventricular hypertrophy.6 , 25 Non-invasive technologies that can be applied at the bedside to improve identification of patients with acute coronary occlusion are needed, but currently lacking. Use of technologies such as body surface mapping28 has been advocated, but these technologies are yet to enter routine practice. Adjunctive imaging with bedside echocardiography29 or computed tomography coronary angiography30 in the Emergency Department have also been proposed, though these require round the clock availability of trained personnel with the relevant expertise, will probably incur significant additional costs, and run the risk of adding delays to the delivery of reperfusion therapy. The cost-effectiveness of utilizing these technologies will need to be shown. High risk ECG patterns suggestive of acute coronary occlusion. Finally, the future answer may yet lie with the simple 12-lead surface ECG. Throughout the world, massive numbers of digitally acquired ECGs are being performed at the time of first medical contact each day for patients with suspected ACS who subsequently undergo coronary angiography. If these were prospectively collated, in the current era of collection and analysis of big data, 12-lead ECGs would be amenable to interrogation by automated machine or deep learning algorithms31 to identify those patterns that are associated with acute coronary occlusion, therefore achieving the desired improved sensitivity and specificity of this simple, cheap, globally available bedside test, and thereby potentially enabling improved access for all patients with acute coronary occlusion to timely reperfusion. Conflicts of interest: R.D.S has no conflict of interest to declare. P.G.S. has received research grants from Merck, Sanofi, and Servier; and speaking or consulting fees from Amarin, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers-Squibb, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, and Servier.