Context-independent identification of myocardial ischemia in the prehospital ECG of chest pain patients.

Non-traumatic chest pain is a frequent reason for an urgent ambulance visit of a patient by the emergency medical services (EMS). Chest pain (or chest pain-equivalent symptoms) can be innocent, but it can also signal an acute form of severe pathology that may require prompt intervention. One of these pathologies is cardiac ischemia, resulting from a disbalance between blood supply and demand. One cause of a diminished blood supply to the heart is acute coronary syndrome (ACS, i.e., cardiac ischemia caused by a reduced blood supply to myocardial tissue due to plaque instability and thrombus formation in a coronary artery). ACS is dangerous due to the unpredictable process that drives the supply problem and the high chance of fast hemodynamic deterioration (i.e., cardiogenic shock, ventricular fibrillation). This is why an ECG is made at first medical contact in most chest pain patients to include or exclude ischemia as the cause of their complaints. For speedy and adequate triaging and treatment, immediate assessment of this prehospital ECG is necessary, still during the ambulance ride. Human diagnostic efforts supported by automated interpretation algorithms seek to answer questions regarding the urgency level, the decision if and towards which healthcare facility the patient should be transported, and the indicated acute treatment and further diagnostics after arrival in the healthcare facility. In the case of an ACS, a catheter intervention room may be activated during the ambulance ride to facilitate the earliest possible in-hospital treatment. Prehospital ECG assessment and the subsequent triaging decisions are complex because chest pain is not uniquely associated with ACS. The differential diagnosis includes other cardiac, pulmonary, vascular, gastrointestinal, orthopedic, and psychological conditions. Some of these conditions may also involve ECG abnormalities. In practice, only a limited fraction (order of magnitude 10%) of the patients who are urgently transported to the hospital because of chest pain are ACS patients. Given the relatively low prevalence of ACS in this patient mix, the specificity of the diagnostic ECG algorithms should be relatively high to prevent overtreatment and overflow of intervention facilities. On the other hand, only a sufficiently high sensitivity warrants adequate therapy when needed. Here, we review how the prehospital ECG can contribute to identifying the presence of myocardial ischemia in chest pain patients. We discuss the various mechanisms of myocardial ischemia and infarction, the typical patient mix of chest pain patients, the shortcomings of the ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) ECG criteria to detect a completely occluded culprit artery, the OMI ECG criteria (including the STEMI-equivalent ECG patterns) in detecting completely occluded culprit arteries, and the promise of neural networks in recognizing ECG patterns that represent complete occlusions. We also discuss the relevance of detecting any ACS/ischemia, not necessarily caused by a total occlusion, in the prehospital ECG. In addition, we discuss how serial prehospital ECGs can contribute to ischemia diagnosis. Finally, we discuss the diagnostic contribution of a serial comparison of the prehospital ECG with a previously made nonischemic ECG of the patient.

Post hoc labeling an acute ECG as ischemic or non-ischemic based on clinical data: A necessary challenge.

The ECG is crucial in the prehospital (and early inhospital) phase of patients with symptoms suggestive of myocardial ischemia. Therefore, new algorithms for ECG-based myocardial ischemia detection are continuously being researched. Development and validation of these algorithms require a database of acute ECGs (from the prehospital or emergency department setting) including a representative mix of cases (ischemia present) and controls (no ischemia present). Therefore, for every patient in this mix, the "truth" regarding the actual presence or absence of myocardial ischemia during the recording of the acute ECG has to be determined to compare the newly developed algorithm against. This post hoc adjudication process of determining whether an acute (either prehospitally acquired or acquired in the emergency department) ECG was made under ischemic conditions should use all available clinical data (the clinical diagnosis, cardiac imaging data, and laboratory values) of the subsequent patient's admission. Even with all data at hand, post hoc labeling a patient and their acute ECG as a myocardial ischemia case or control cannot be forced into a binary division between definite cases and definite controls. More specifically, to be used for the development of a new algorithm, the patients' ECG has to be scored for the presence or absence of myocardial ischemia at the exact moment of its recording, which renders the classification even more difficult. For instance, even though it may be plausible that myocardial ischemia was present at a given moment during the patient's admission, this is not necessarily proof that the prehospital (or early inhospital) ECG was also made in ischemic conditions: ischemia can be a fluctuating process (as is, e.g., the case in unstable angina pectoris). Therefore, post hoc classification of an acute ECG in terms of the absence or presence of ischemia requires a multipoint scale ranging between definite ischemic to definite non-ischemic, for instance using a 5-point scale (presumed non-ischemic, probably non-ischemic, uncertain, probably ischemic, presumed ischemic). To summarize, the post hoc adjudication process of ECGs of ambulance (and emergency department) patients cannot result in a binary division into definite cases and controls (i.e., patients with or without myocardial ischemia during the recording of the acute ECG), as myocardial ischemia is often dynamic rather than constant. ECGs could be labeled on a multi-point scale, in which the label represents the probability of the actual presence (or absence) of myocardial ischemia at the exact moment of the recording of that ECG. Further development of algorithms for myocardial ischemia detection should consider this concept.

Advanced repeated structuring and learning procedure to detect acute myocardial ischemia in serial 12-lead ECGs.

Objectives. Acute myocardial ischemia in the setting of acute coronary syndrome (ACS) may lead to myocardial infarction. Therefore, timely decisions, already in the pre-hospital phase, are crucial to preserving cardiac function as much as possible. Serial electrocardiography, a comparison of the acute electrocardiogram with a previously recorded (reference) ECG of the same patient, aids in identifying ischemia-induced electrocardiographic changes by correcting for interindividual ECG variability. Recently, the combination of deep learning and serial electrocardiography provided promising results in detecting emerging cardiac diseases; thus, the aim of our current study is the application of our novel Advanced Repeated Structuring and Learning Procedure (AdvRS&LP), specifically designed for acute myocardial ischemia detection in the pre-hospital phase by using serial ECG features.Approach. Data belong to the SUBTRACT study, which includes 1425 ECG pairs, 194 (14%) ACS patients, and 1035 (73%) controls. Each ECG pair was characterized by 28 serial features that, with sex and age, constituted the inputs of the AdvRS&LP, an automatic constructive procedure for creating supervised neural networks (NN). We created 100 NNs to compensate for statistical fluctuations due to random data divisions of a limited dataset. We compared the performance of the obtained NNs to a logistic regression (LR) procedure and the Glasgow program (Uni-G) in terms of area-under-the-curve (AUC) of the receiver-operating-characteristic curve, sensitivity (SE), and specificity (SP).Main Results. NNs (median AUC = 83%, median SE = 77%, and median SP = 89%) presented a statistically (Pvalue lower than 0.05) higher testing performance than those presented by LR (median AUC = 80%, median SE = 67%, and median SP = 81%) and by the Uni-G algorithm (median SE = 72% and median SP = 82%).Significance. In conclusion, the positive results underscore the value of serial ECG comparison in ischemia detection, and NNs created by AdvRS&LP seem to be reliable tools in terms of generalization and clinical applicability.

Do sex differences in the prevalence of ECG abnormalities vary across ethnic groups living in the Netherlands? A cross-sectional analysis of the population-based HELIUS study.

OBJECTIVES: Major ECG abnormalities have been associated with increased risk of cardiovascular disease (CVD) burden in asymptomatic populations. However, sex differences in occurrence of major ECG abnormalities have been poorly studied, particularly across ethnic groups. The objectives were to investigate (1) sex differences in the prevalence of major and, as a secondary outcome, minor ECG abnormalities, (2) whether patterns of sex differences varied across ethnic groups, by age and (3) to what extent conventional cardiovascular risk factors contributed to observed sex differences. DESIGN: Cross-sectional analysis of population-based study. SETTING: Multi-ethnic, population-based Healthy Life in an Urban Setting cohort, Amsterdam, the Netherlands. PARTICIPANTS: 8089 men and 11 369 women of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin aged 18-70 years without CVD. OUTCOME MEASURES: Age-adjusted and multivariable logistic regression analyses were performed to study sex differences in prevalence of major and, as secondary outcome, minor ECG abnormalities in the overall population, across ethnic groups and by age-groups (18-35, 36-50 and >50 years). RESULTS: Major and minor ECG abnormalities were less prevalent in women than men (4.6% vs 6.6% and 23.8% vs 39.8%, respectively). After adjustment for conventional risk factors, sex differences in major abnormalities were smaller in ethnic minority groups (OR ranged from 0.61 in Moroccans to 1.32 in South-Asian Surinamese) than in the Dutch (OR 0.49; 95% CI 0.36 to 0.65). Only in South-Asian Surinamese, women did not have a lower odds than men (OR 1.32; 95% CI 0.96 to 1.84). The pattern of smaller sex differences in ethnic minority groups was more pronounced in older than in younger age-groups. CONCLUSIONS: The prevalence of major ECG abnormalities was lower in women than men. However, sex differences were less apparent in ethnic minority groups. Conventional risk factors did not contribute substantially to observed sex differences.

Prevalence of ECGs Exceeding Thresholds for ST-Segment-Elevation Myocardial Infarction in Apparently Healthy Individuals: The Role of Ethnicity.

Background Early prehospital recognition of critical conditions such as ST-segment-elevation myocardial infarction (STEMI) has prognostic relevance. Current international electrocardiographic STEMI thresholds are predominantly based on individuals of Western European descent. However, because of ethnic electrocardiographic variability both in health and disease, there is a need to reevaluate diagnostic ST-segment elevation thresholds for different populations. We hypothesized that fulfillment of ST-segment elevation thresholds of STEMI criteria (STE-ECGs) in apparently healthy individuals is ethnicity dependent. Methods and Results HELIUS (Healthy Life in an Urban Setting) is a multiethnic cohort study including 10 783 apparently healthy subjects of 6 different ethnicities (African Surinamese, Dutch, Ghanaian, Moroccan, South Asian Surinamese, and Turkish). Prevalence of STE-ECGs across ethnicities, sexes, and age groups was assessed with respect to the 2 international STEMI thresholds: sex and age specific versus sex specific. Mean prevalence of STE-ECGs was 2.8% to 3.4% (age/sex-specific and sex-specific thresholds, respectively), although with large ethnicity-dependent variability. Prevalences in Western European Dutch were 2.3% to 3.0%, but excessively higher in young (<40 years) Ghanaian males (21.7%-27.5%) and lowest in older (≥40 years) Turkish females (0.0%). Ethnicity (sub-Saharan African origin) and other variables (eg, younger age, male sex, high QRS voltages, or anterolateral early repolarization pattern) were positively associated with STE-ECG occurrence, resulting in subgroups with >45% STE-ECGs. Conclusions The accuracy of diagnostic tests partly relies on background prevalence in healthy individuals. In apparently healthy subjects, there is a highly variable ethnicity-dependent prevalence of ECGs with ST-segment elevations exceeding STEMI thresholds. This has potential consequences for STEMI evaluations in individuals who are not of Western European descent, putatively resulting in adverse outcomes with both over- and underdiagnosis of STEMI.

Serial electrocardiography to detect newly emerging or aggravating cardiac pathology: a deep-learning approach.

BACKGROUND: Serial electrocardiography aims to contribute to electrocardiogram (ECG) diagnosis by comparing the ECG under consideration with a previously made ECG in the same individual. Here, we present a novel algorithm to construct dedicated deep-learning neural networks (NNs) that are specialized in detecting newly emerging or aggravating existing cardiac pathology in serial ECGs. METHODS: We developed a novel deep-learning method for serial ECG analysis and tested its performance in detection of heart failure in post-infarction patients, and in the detection of ischemia in patients who underwent elective percutaneous coronary intervention. Core of the method is the repeated structuring and learning procedure that, when fed with 13 serial ECG difference features (intra-individual differences in: QRS duration; QT interval; QRS maximum; T-wave maximum; QRS integral; T-wave integral; QRS complexity; T-wave complexity; ventricular gradient; QRS-T spatial angle; heart rate; J-point amplitude; and T-wave symmetry), dynamically creates a NN of at most three hidden layers. An optimization process reduces the possibility of obtaining an inefficient NN due to adverse initialization. RESULTS: Application of our method to the two clinical ECG databases yielded 3-layer NN architectures, both showing high testing performances (areas under the receiver operating curves were 84% and 83%, respectively). CONCLUSIONS: Our method was successful in two different clinical serial ECG applications. Further studies will investigate if other problem-specific NNs can successfully be constructed, and even if it will be possible to construct a universal NN to detect any pathologic ECG change.

Position of ST-deviation measurements relative to the J-point: Impact for ischemia detection.

BACKGROUND: There is no consensus about the time instant relative to the J point where ST deviation has to be measured for detection of acute ischemia in the ECG. METHODS: We analyzed 53 ECGs, recorded preceding emergency catheterization of acute coronary syndrome patients with a completely occluded culprit artery (cases), and 88 control ECGs recorded in the cardiology outpatient clinic. ECG-amplitude measurements were made every 10 ms, between 20 ms before till 80 ms after the J point. STEMI-detection algorithms varied from the traditional STEMI criterion (elevations in at least two adjacent ECG leads), via the STEMI equivalent criterion (depressions in V2 and V3), to the most liberal STEMI-detection algorithm in which elevations as well as depressions in two adjacent leads were considered as signs of ischemia. RESULTS: Diagnostic accuracy was highest (93.6%) for the most liberal STEMI-detection algorithm at 10 ms after the J point; sensitivity was 94.3% and specificity was 93.2%. CONCLUSION: The results of our study suggest that STEMI detection close to the J point is optimal.

Subtraction electrocardiography: Detection of ischemia-induced ST displacement without the need to identify the J point.

BACKGROUND: When triaging a patient with acute chest pain at first medical contact, an electrocardiogram (ECG) is routinely made and inspected for signs of myocardial ischemia. The guidelines recommend comparison of the acute and an earlier-made ECG, when available. No concrete recommendations for this comparison exist, neither is known how to handle J-point identification difficulties. Here we present a J-point independent method for such a comparison. METHODS: After conversion to vectorcardiograms, baseline and acute ischemic ECGs after 3minutes of balloon occlusion during elective PCI were compared in 81 patients of the STAFF III ECG database. Baseline vectorcardiograms were subtracted from ischemic vectorcardiograms using either the QRS onsets or the J points as synchronization instants, yielding vector magnitude difference signals, ΔH. Output variables for the J-point synchronized differences were ΔH at the actual J point and at 20, 40, 60 and 80ms thereafter. Output variables for the onset-QRS synchronized differences were the ΔH at 80, 100, 120, 140 and 160ms after onset QRS. Finally, linear regressions of all combinations of ΔHJ+… versus ΔHQRS+… were made, and the best combination was identified. RESULTS: The highest correlation, 0.93 (p<0.01), was found between ΔH 40ms after the J point and 160ms after the onset of the QRS complex. With a ΔH ischemia threshold of 0.05mV, 66/81 (J-point synchronized differences) and 68/81 (onset-QRS synchronized differences) subjects were above the ischemia threshold, corresponding to sensitivities of 81% and 84%, respectively. CONCLUSION: Our current study opens an alternative way to detect cardiac ischemia without the need for human expertise for determination of the J point by measuring the difference vector magnitude at 160ms after the onset of the QRS complex.

Performance of ST and ventricular gradient difference vectors in electrocardiographic detection of acute myocardial ischemia.

INTRODUCTION: Serial analysis could improve ECG diagnosis of myocardial ischemia caused by acute coronary occlusion. METHODS: We analyzed ECG pairs of 84 cases and 398 controls. In case-patients, who underwent elective percutaneous coronary intervention, ischemic ECGs during balloon occlusion were compared with preceding non-ischemic ECGs. In control-patients, two elective non-ischemic ECGs were compared. In each ECG the ST vector at the J point and the ventricular gradient (VG) vector was computed, after which difference vectors ΔST and ΔVG were computed within patients. Finally, receiver operating characteristic analysis was done. RESULTS: Areas under the curve were 0.906 (P<0.001; CI 0.862-0.949; SE 0.022) for ΔST and 0.880 (P<0.001; CI 0.833-0.926; SE 0.024) for ΔVG. Sensitivity and specificity of conventional ST-elevation myocardial infarction (STEMI) criteria were 70.2% and 89.1%, respectively. At matched serial analysis specificity and STEMI specificity, serial analysis sensitivity was 78.6% for ΔST and 71.4% for ΔVG (not significantly different from STEMI sensitivity). At matched serial analysis sensitivity and STEMI sensitivity, serial analysis specificity was 96.5% for ΔST and 89.3% for ΔVG; ΔST and STEMI specificities differed significantly (P<0.001). CONCLUSION: Detection of acute myocardial ischemia by serial ECG analysis of ST and VG vectors has equal or even superior performance than the STEMI criteria. This concept should be further evaluated in triage ECGs of patients suspected from having acute myocardial ischemia.

Intra-individual ECG changes over 25 years: How long can elective ECGs be used as reference for acute ischemia detection?

BACKGROUND: The guidelines advocate, in patients with chest pain, comparison of the acute ECG with a previously made, non-ischemic ECG that serves as a reference, to corroborate the working diagnosis of acute coronary syndrome (ACS). Our approach of this serial comparison is to compute the differences between the ST vectors at the J point and 60 ms thereafter (∆ST(J+0), ∆ST(J+60)) and between the ventricular gradient (VG) vectors (∆VG). In the current study, we investigate if reference ECGs remain valid in time. METHODS: We studied 6 elective non-ischemic ECGs (ECG0, ECG1, …, ECG5), 5 years apart, in 88 patients. Within each patient, serial comparisons were done 1) between all successive ECGs, and 2) between each of ECG1, ECG2, …, ECG5 and ECG0, computing, in addition to ∆ST(J+0), ∆ST(J+60) and ∆VG, the difference in heart rates, ∆HR. Additionally, relevant clinical events and the diagnoses associated with each ECG were collected. Linear regression was used to assess trends in ∆ST(J+0), ∆ST(J+60) and ∆VG; multiple linear regression was used to assess the influence of the clinical events and diagnoses on ∆ST(J+0), ∆ST(J+60) and ∆VG. RESULTS: There were no trends in the differences between successive ECGs. Positive trends were seen with increasing time lapses between ECGs: ∆ST(J+0), ∆ST(J+60) and ∆VG increased per year by 0.65 µV, 1.45 µV and 3.69 mV∙ms, respectively. Extrapolation to a time lapse of 0 yielded 50.92 µV, 36.63 µV and 20.91 mV∙ms for the short-term reproducibility of ∆ST(J+0), ∆ST(J+60) and ∆VG, respectively. Multiple linear regression revealed that clinical variables could explain only 10%, 17% and 13% of the variability in ∆ST(J+0), ∆ST(J+60) and ∆VG, respectively. CONCLUSION: With a view on ischemia detection thresholds in the order of magnitude of 58 µV for ∆ST and 26 mV·ms for ∆VG, our study suggests that it is important to have a recent ECG available for the detection of myocardial ischemia, as an "aged" ECG may have lost its validity as a reference.

Directionality and proportionality of the ST and ventricular gradient difference vectors during acute ischemia.

BACKGROUND: The ECG is important in diagnosis and triage in the initial phase of the acute coronary syndrome (ACS). The primary goal of making an ECG at first medical contact should be the reliable detection of cardiac ischemia, thus facilitating a correct triage by corroborating the diagnosis of ACS. Ischemia detection by ST amplitude analysis is limited to situations in which there is an identifiable J point. The ventricular gradient (VG) is independent of conduction and might be an alternative ECG-based variable for ischemia detection. METHODS: We studied vectorcardiograms (VCGs) synthesized of the ECGs of 67 patients who underwent elective PTCA with prolonged balloon occlusions (mean±SD occlusion duration 214±77s), and computed, during occlusions, the changes of the ST and VG vectors with respect to baseline, ΔST and ΔVG, and the angle between these vectors, ∠(ΔST, ΔVG). We then analyzed directionality and proportionality of ΔST and ΔVG by performing linear regressions of ∠(ΔST, ΔVG) on time after occlusion, and of ΔVG on ΔST, respectively. RESULTS: Linear regression of ∠(ΔST, ΔVG) on time after occlusion yielded a slope of 1.55*10(-3) °/s and an intercept of 11.96°; r(2)<0.001 (NS). Linear regression of ΔVG on ΔST on all data yielded a slope of 253mV and an intercept of 14.4mV•ms; r(2)=0.75 (P<0.001). Broken stick linear regression (breakpoint ΔST=0.255mV) yielded slopes of 330mV and 160mV, intercepts of 5.6mV•ms and 47.2mV•ms, and r(2) values of 0.66 (P<0.001) and 0.63 (P<0.001) for the smaller and larger ΔST values, respectively. CONCLUSION: Our study suggests that, because of the directionality and proportionality between ΔST and ΔVG, the change in the ventricular gradient, ΔVG, between a reference ECG and an ischemic ECG is a meaningful measure of ischemia.

Difference vectors to describe dynamics of the ST segment and the ventricular gradient in acute ischemia.

BACKGROUND: The ECG is important in the diagnosis and triage of the acute coronary syndrome (ACS), especially in the hyperacute phase, the "golden hours," during which myocardial salvage possibilities are largest. An important triaging decision to be taken is whether or not a patient requires primary PCI, for which, as mentioned in the guidelines, the presence of an ST elevation (STE) pattern in the ECG is a major criterion. However, preexisting non-zero ST amplitudes (diagnostic, but also non-diagnostic) can obscure or even preclude this diagnosis. METHODS: In this study, we investigated the potential diagnostic possibilities of ischemia detection by means of changes in the ST vector, ΔST, and changes in the VG (QRST integral) vector, ΔVG. We studied the vectorcardiograms (VCGs) synthesized of the ECGs of 84 patients who underwent elective PTCA. Mean±SD balloon occlusion times were 260±76s. The ECG ischemia diagnosis (ST elevation, STE, or non-ST-elevation, NSTE), magnitudes and orientations of the ST and VG vectors, and the differences ΔST and ΔVG with the baseline ECG were measured after 3min of balloon occlusion. RESULTS: Planar angles between the ΔST and ΔVG vectors were 14.9±14.0°. Linear regression of ΔVG on ΔST yielded ΔVG=324·ΔST (r=0.85; P<0.0001, ΔST in mV). We adopted ΔST>0.05mV, and the corresponding ΔVG>16.2mV·ms as ischemia thresholds. The classical criteria characterized the ECGs of 46/84 (55%) patients after 3min of occlusion as STE ECGs. Combined application of the ΔST and ΔVG criteria identified 73/84 (87%) of the patients as ischemic. CONCLUSION: Differential diagnosis by ΔST and ΔVG (requiring an earlier made non-ischemic baseline ECG) could dramatically improve ECG guided detection of patients who urgently require catheter intervention.