American Journal of Emergency Medicine xxx (2014) xxx–xxx

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American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem

Original Contribution

Comparison of exercise electrocardiogram and exercise echocardiography in intermediate-risk chest pain patients Alberto Conti, MD a,⁎, Andrea Alesi, MD a, Giovanna Aspesi, MD a, Sofia Bigiarini, MD a, Simone Bianchi, MD a, Elena Angeli, MD a, Maurizio Zanobetti, MD b, Francesca Innocenti, MD b, Riccardo Pini, MD b, Gian Franco Gensini, MD c a b c

Emergency Medicine and Chest Pain Clinic, Department of Critical Care Medicine and Surgery, Careggi University Hospital, Florence, Italy Emergency Medicine, Department of Critical Care Medicine and Surgery, Careggi University Hospital, Florence, Italy Department of Cardiology, Careggi University Hospital, Florence, Italy

a r t i c l e

i n f o

Article history: Received 12 June 2014 Received in revised form 23 September 2014 Accepted 24 September 2014 Available online xxxx

a b s t r a c t Background: The novel exercise computer-assisted high-frequency QRS analysis (HF/QRS) has demonstrated improved sensitivity and specificity over the conventional ST/electrocardiogram-segment analysis (ST/ECG) in the detection of myocardial ischemia. The aim of the present study was to compare the diagnostic value of the validated exercise echocardiography (ex-Echo) with the novel exercise ECG (ex-ECG) including HF/QRS and ST/ECG analysis. Methods: A prospective cohort study was conducted in the emergency department of a tertiary care teaching Hospital. Patients with chest pain (CP), normal resting ECGs, troponins, and echocardiography, labeled as “intermediate-risk” for adverse coronary events, underwent the novel ex-ECG and ex-Echo. An ST-segment depression of at least 2 mV or at least 1 mV when associated with CP was considered as an index of ischemia, as well as a decrease of at least 50% in HF/QRS intensity, or new wall motion abnormalities on ex-Echo. Exclusion criteria were QRS duration of at least 120 milliseconds, poor echo-acoustic window, and inability to exercise. Patients were followed up to 3 months. The end point was the composite of coronary stenoses of 50% or greater at angiography or acute coronary syndrome, revascularization, and cardiovascular death on the 3-month follow-up. Results: Of 188 patients enrolled, 18 achieved the end point. The novel ex-ECG and ex-Echo showed comparable negative predictive value (97% vs 96%; P = .930); however, sensitivity was 83% vs 61%, respectively (P = .612), and specificity was 64% vs 92%, respectively,(P = .026). The areas on receiver operating characteristic analysis were comparable (ex-ECG: 0.734 [95% confidence interval, or CI, 0.62-0.85] vs ex-Echo: 0.767 [CI, 0.63-0.91]; C statistic, P = .167). On multivariate analysis, both ex-ECG (hazard ratio, 5; CI, 1-20; P = .017) and ex-Echo (HR, 12; CI, 4-40; P b .001) were predictors of the end point. Conclusions: In intermediate-risk CP patients, the novel ex-ECG including HF/QRS added to ST/ECG analysis was a valuable diagnostic tool and might be proposed to avoid additional imaging. However, the novel test needs additional study before it can be recommended as a replacement for current techniques. © 2014 Elsevier Inc. All rights reserved.

1. Introduction The exercise echocardiography (ex-Echo), exercise stress myocardial perfusion imaging, and coronary computed tomography angiography (CTA) have shown higher diagnostic values over the exercise tolerance test in the diagnosis of stress-induced ischemia. Indeed, the sensitivity and specificity for coronary disease of the exercise tolerance test are reported to be up to 50% and 90%, respectively, compared with 85% and 88% of ex-Echo, 92% and 97% of exercise stress myocardial perfusion imaging, and 99% and 83% of CTA, respectively [1]. However, the exercise tolerance test is widely available, is less expensive, and avoids ⁎ Corresponding author at: Emergency Medicine and Chest Pain Clinic, Department of Critical Care Medicine and Surgery, Careggi University Hospital, Florence, Italy. E-mail addresses: [email protected], [email protected] (A. Conti).

ionizing radiation, whereas nuclear scan, stress echocardiography, and CTA require specific expertise and time-sensitive availability. Thus, in patients with chest pain and nondiagnostic electrocardiograms (ECGs) and normal troponin levels, which tests should be used is still under debate. Because of the increasing imbalance between infinite demand and finite resources, we need to consider pretest probability and test sensitivity or specificity to the threshold approach to clinical decision making [2]. In the emergency setting, the validated exercise tolerance test is still considered the optimal first-line test for risk/assessment in intermediate-risk patients with suspected myocardial ischemia [3,4]. Recently, the automated computer-assisted analysis of high-frequency mid-QRS components during exercise (ex-HF/QRS) has been proposed for diagnostic in chest pain patients referred for exercise tolerance test. This novel electrocardiographic technique allows the detection of stress-induced ischemia by examining the high-frequency QRS

http://dx.doi.org/10.1016/j.ajem.2014.09.035 0735-6757/© 2014 Elsevier Inc. All rights reserved.

Please cite this article as: Conti A, et al, Comparison of exercise electrocardiogram and exercise echocardiography in intermediate-risk chest pain patients, Am J Emerg Med (2014), http://dx.doi.org/10.1016/j.ajem.2014.09.035

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A. Conti et al. / American Journal of Emergency Medicine xxx (2014) xxx–xxx

components in the 150- to 250-Hz frequency band [5–9]. During depolarization, the myocardium is activated via myocyte-to-myocyte conduction, spreading away from the ends of the Purkinje fibers. The depolarization wavefront, which creates the QRS complex, is fragmented on the microscopic level. This fragmentation brings about low-amplitude, high-frequency notches on the QRS. Ischemia slows down myocyte-to-myocyte conduction due to changes in the action potential of ischemic myocytes. The slow conduction reduces the fragmentation of the depolarization wavefront and thus shifts the highfrequency components to lower frequencies. Consequently, ischemia results in high-frequency QRS intensity reduction. Thus, depolarization changes during exercise using an automated analysis of highfrequency QRS components allow for detection of ischemia better than identification of ST-segment deviations [9–11]. The technique has demonstrated improved sensitivity and specificity over the conventional ST-segment analysis. Nevertheless, the value of this novel technique in an emergency setting has not been validated yet. The aim of this study was to analyze and compare the diagnostic value of the novel exercise ECG (ex-ECG), including the HF/QRS and ex-ST/ECG analysis, with the ex-Echo in patients with chest pain and normal resting ECGs, troponin, and echocardiography. 2. Methods 2.1. Study population Unselected consecutive patients with typical visceral chest pain were enrolled between January and December 2013. The cohort of patients was prospectively evaluated in the emergency department of the tertiary care teaching Careggi-Hospital, in Florence, Italy, with a catchment area of half a million patients. The inclusion criterion was the presence of visceral chest pain consistent for angina pectoris lasting less than 24 hours, resting normal ECGs, troponins, and echocardiography after the first-line evaluation, including an observation period of 6 to 12 hours. The presence of hemodynamic instability (ie, systolic blood pressure b100 mm Hg) or Killip class of 2 or higher, or the presence of acute coronary syndrome or stroke represented exclusion criteria. Patients with wide QRS (ie, cardiac pacemaker or QRS duration ≥120 milliseconds), poor echo-acoustic window, and inability to exercise were also excluded because we performed an analysis of ex-ECG and echocardiography. In addition, we excluded patients with comorbidities such as renal impairment and chronic obstructive pulmonary disease known to be moderate to severe or end-stage. Finally, patients with abnormal troponin plasma levels (ie, ≥ 0.10 ng/mL, as the 99th percentile of a control group, representing the cutoff value of our core laboratory in high-sensitivity assay cardiac troponin I from ADVIA Centaur TnI-Ultra, by Siemens Aktiengesellschaft, Munich, Germany) [12] were excluded. Tourists and inhabitants outside the catchment area of Careggi Hospital were not enrolled in the study because of the high probability of losing them at follow-up. 2.2. Management of patients Clinical evaluation, including assessment of lifestyle, comorbidities, physical examination, and serial blood tests including troponin, was performed in all patients. Patients with negative evaluation were subjected, just on presentation, to an observation period of 6 to 12 hours with serial ECGs, serial cardiac troponin I tests, and resting echocardiography [3,13–15] in order to be considered for enrollment. The Department of Cardiology was on call for serial evaluation. Chest pain was characterized with a validated chest pain score which takes into account pain characteristics (crushing, pressing, heaviness = 3; sticking, pleuritic, pinprick = 1), localization (substernal or precordial = 3; epigastric, left chest, neck, lower jaw = 1), radiation (as arm, shoulder, back, neck, or lower jaw = 1; absence = 0), associated symptoms (as

dyspnea, nausea, diaphoresis = 2; absence = 0), and recurrence in the previous 48 hours (yes = 3, no = 0) [16,17]. The selected patients presented a pretest likelihood of coronary artery disease between 15% and 85% calculated using a model based on age, sex, smoking, diabetes, hyperlipidemia, baseline ECG abnormalities, type of chest pain, and history of myocardial infarction [18,19]. Patients were considered as having a resting normal ECG in the presence of normal ST segment, measured at 60 milliseconds from J point, and normal T-wave. Patients were considered as having a nondiagnostic ECG in the presence of mild changes such as ST-segment elevation or depression less than 0.05 mV, or asymmetrical T-wave inversion less than 0.2 mV, and no Q wave or Q waves less than 0.03 seconds. The diagnosis of acute coronary syndrome was considered in the presence of a ST-segment depression of at least 0.1 mV or STsegment elevation of at least 0.1 mV in 2 contiguous electrocardiographic leads, at least, measured at 60 milliseconds from J point, according to the European and North American Guidelines [1,20,21]. Troponin I test was performed on presentation and after 3 to 6 hours or up to 12 hours, as required by clinical evolution; troponin test was repeated with the same modality if patients complained of recurrent chest pain. Patients showing ischemic ECG changes or troponin elevations, or new cardiac wall motion abnormalities at echocardiography on presentation or during the first-line evaluation were considered at high risk for cardiac events; they were admitted. Patients with negative ECGs, troponins, and normal echocardiography were considered at “intermediaterisk” for coronary events; they were enrolled and underwent ex-ECG. Each patient gave informed consent to participate in the study and publication of personal data. The study was conducted according to the good clinical practice and principles of the Declaration of Helsinki of clinical research involving human patients. The institutional review board approved the protocol. Departmental sources supported the work, and no contributorship or competing interest existed. 2.3. Stress testing Each patient underwent maximal ex-ECG for conventional STsegment analysis by the physician on duty and ex-HF/QRS for automated computer-assisted high-frequency QRS analysis; at the same time, patients underwent ex-Echo for wall motion analysis [4,10,22–24]. The ex-ECG was performed early after the first 6 to 12 hours of observation and not longer than 24 hours from presentation. The exercise tolerance test was performed according to the standard Bruce protocol, aiming to reach at least 85% of the age-adjusted maximal predicted heart rate (% of maximal predicted heart rate: (220 − age in years) × 0.85). The test was prematurely terminated in the presence of angina associated with ST-segment depression of at least 0.1 mV, or with STsegment depression of at least 0.2 mV without angina, ventricular tachycardia, systolic blood pressure greater than 250 mm Hg, or decrease in systolic blood pressure during exercise. The test was considered normal if 85% of the maximal predicted heart rate was reached without symptoms, ECG changes, and echocardiographic abnormalities. Peak exercise capacity from the treadmill test was estimated in metabolic equivalents (METs), using data from standard predicted equations [3,25]. A high-resolution 12-lead ECG (HyperQ Stress System; BSP Ltd, Tel Aviv, Israel) was continuously recorded throughout the exercise test and used for offline automated computer-assisted quantitative assessment of ST-segment changes and HF/QRS analysis. Conventional ECG monitoring during the exercise test was evaluated simultaneously by the physician on duty and extracted automatically from the highresolution ECG traces. In both automated and conventional assessment, the ST-segment level was measured 60 milliseconds after the J point. Overall, diagnostic results were considered to be not accessible in cases of unavailability of optimal technical analysis of HF/QRS. The STsegment analysis was considered positive in the presence of STsegment depression of at least 0.2 mV or ST-segment depression of at least 0.1 mV when associated with chest pain, in 2 contiguous leads at least. The HF/QRS intensity was calculated, and a decrease of at least

Please cite this article as: Conti A, et al, Comparison of exercise electrocardiogram and exercise echocardiography in intermediate-risk chest pain patients, Am J Emerg Med (2014), http://dx.doi.org/10.1016/j.ajem.2014.09.035

A. Conti et al. / American Journal of Emergency Medicine xxx (2014) xxx–xxx

50% of the signal recorded in 2 contiguous leads was considered as index of ischemia. The ex-ECG analysis was considered positive when ST/QRS or HF/QRS analysis was found to be positive. Echocardiography was acquired before and immediately after exercise testing. The echocardiographic images in the parasternal long- and short-axis and apical 4- and 2-chambers view were collected to allow quad-screen visualization (iE33; Philips Medical System, Andover, MA). The ex-Echo was considered positive if new or worsening wall motion abnormalities were identified, regardless of the presence of symptoms or ECG changes. Patients recognized as having positive ex-ECG or positive ex-Echo results were considered at high risk for cardiac events; they were admitted and considered for angiography. Patients with negative stress test results were considered at very low risk for coronary events; they were discharged home and submitted to short-term follow-up. 2.4. End point The end point was the composite of coronary artery stenosis of at least 50% at angiography or the occurrence of ischemic cardiac events including acute coronary syndrome, revascularization, and cardiovascular death within the 3-month follow-up. 2.5. Follow-up All patients were subjected to follow-up by telephone after 3 months. Data were collected by means of a physician-led telephone interview using a standardized questionnaire. Each event of suspected myocardial ischemia was analyzed and confirmed after clinical medical record, ECG, and laboratory test review. 2.6. Statistical analysis Continuous variables are expressed as mean ± SD. Frequencies are shown as absolute values and percentages. Statistical comparisons of demographic and clinical features between the groups of patients enrolled in the study and between the groups of patients who reached or did not reach the primary end point were performed using the χ 2 test (Fisher exact test) when expected frequencies were less than 5% and the Pearson exact test for categorical variables. Continuous variables were compared through 1-way analysis of variance and t test. Two-tail P value less than .05 was considered statistically significant. Univariate analysis was performed in a full-factorial model to provide regression; indeed, in stepwise discriminant analysis, the incidence at follow-up of the composite end point was adjusted for all covariates. Variables identified as potential prognostic predictors for multivariate modeling were selected by backward method (likelihood ratio method, with variable in by P b .05 and out P N .10 to avoid biases due to collinearity). Hazard ratios were used to illustrate the probabilities of adverse events. This analysis was used to define any independent predictors of the end point. In addition, to estimate the predictive power of single tests for predicting the presence or absence of disease, sensitivity, specificity, positive (+) and negative (−) predictive values, and likelihood ratios (LRs; (+)LR = sensitivity/(1 − specificity); (−)LR = specificity/(1 − sensitivity)) were calculated using follow-up data. Pairwise comparison of receiver operating characteristic (ROC) curves was performed using the C statistic test. Calculations were performed with the use of version 19, SPSS Statistical Package (SPSS Inc, Chicago, IL) for all analyses. 3. Results 3.1. Study population Of 377 chest pain patients with nondiagnostic first-line screening for coronary disease, 11 were excluded due to the presence of wide QRS, 28 for unavailability of optimal technical HF/QRS analysis due to

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noisy, 60 for poor echo-acoustic window, and 90 for inability to exercise. Thus, 188 patients were enrolled (mean age, 59 ± 16 years; range, 1887 years; 128 men). The time to enrollment and outcomes are shown in Fig. 1. Baseline clinical characteristics of patients who achieved or did not achieve the composite end point have been analyzed and are shown in Table 1. Patients were also stratified according to the results of stress testing. The final analysis covers 83 patients who resulted in having, at least, 1 of 2 positive stress test results. Of these, 15 reached the end point; conversely, of 105 patients with negative stress test results, 3 reached the end point. No patients were lost at follow-up. Patients with positive test results were more likely to present known existing cardiovascular disease inclusive of coronary artery disease, stroke, and peripheral artery disease, antiplatelets, and angiotensinconverting enzyme inhibitors use. Factors associated with adverse outcome are shown in Table 2: only positive ex-ECG and ex-Echo results were am independent predictor of the end point on multivariate analysis. 3.2. Predictive values of stress testing The novel ex-ECG analysis (including the HF/QRS analysis and the conventional ST/QRS analysis) when compared with ex-Echo showed comparable negative predictive value (97% vs 96%, respectively; P = .930); however, the difference in sensitivity was not statistically significant (83% vs 61%, respectively; P = .612), and the difference in specificity was lower (64% vs 92%, respectively; P b .026; Fig. 2). Although the difference in sensitivity between the 2 tests did not reach statistical significance, a relative improvement favored the novel ex-ECG by 36% (61:100 = 83:X, 136%; ie, up to 36% more sensitivity with novel ex-ECG analysis when compared with ex-Echo in detection of highrisk patients for the end point). Meanwhile, ex-Echo showed a relative improvement in specificity by 44%. Of note, general results were more likely to due to HF/QRS analysis than the conventional ex-ST/ECG analysis; indeed the ex-HF/QRS analysis, alone, was more sensitive than the conventional ex-ST/ECG analysis alone (72% vs 33%, respectively; P = .256), but less specific (76% vs 96%, respectively; P b .023). Finally, the negative predictive value of HF/QRS analysis was comparable to the other techniques (96% in ex-HF/QRS, 93% in ex-ST/ECG, and 96% in ex-echo). 3.3. Receiver operating characteristic analysis On the ROC analysis for the composite end point, both the novel exECG and the ex-Echo showed an incremental diagnostic value over clinical parameters (Fig. 3) and over the conventional exercise tolerance test (Table 3). On C statistic analysis, no differences were found among the 3 different ROC curves (ex-ECG vs ex-Echo, 0.167; ex-ECG vs CPS N7, 0.412; ex-Echo vs CPS N 7, 0.967). 4. Discussion 4.1. Main findings This study analyses the diagnostic value of the novel ex-ECG including the high-frequency QRS analysis associated with the conventional ST-segment analysis in exercise-induced myocardial ischemia. The technique has been proposed in intermediate-risk chest pain patients characterized by nondiagnostic first-line evaluation for coronary artery disease. In these patients, with a substantial incidence of adverse coronary events, the conventional ST-segment analysis has shown poor diagnostic value [1,17,23,26]. The present study provides information to support evidence that a normal result of the novel ex-ECG was statistically comparable with ex-Echo in recognizing patients at “low-risk” for short-term cardiac events. Of note, ex-ECG showed a relative improvement in sensitivity up to 36% and eventually favored safe discharge. Nonetheless, ex-Echo showed significant diagnostic specificity up to 44% higher than ex-ECG and favored admission in cardiology.

Please cite this article as: Conti A, et al, Comparison of exercise electrocardiogram and exercise echocardiography in intermediate-risk chest pain patients, Am J Emerg Med (2014), http://dx.doi.org/10.1016/j.ajem.2014.09.035

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A. Conti et al. / American Journal of Emergency Medicine xxx (2014) xxx–xxx

Fig. 1. The chart of time to management and outcomes in intermediate-risk chest pain patients enrolled in the study according to the occurrence of the end point inclusive of coronary stenosis of 50% or greater at angiography or myocardial infarction, revascularization, and cardiac death at follow-up.

Table 1 Baseline clinical characteristics of patients with chest pain and negative first-line screening for coronary artery disease enrolled in the study (n = 188) according to the occurrence of the primary end point inclusive of coronary stenosis ≥50% at angiography or myocardial infarction, revascularization, and cardiac death at follow-up Parameter

Patients (n = 188)

Reach the end point (n = 18)

Do not reach the end point (n = 170)

P

Age (y), mean ± SD Male sex, n (%) Hypertension, n (%) Diabetes mellitus, n (%) Hypercholesterolemia, n (%) Active smokers, n (%) Known cardiovascular disease, n (%) Familiarity for coronary artery disease, n (%) Chest pain score, mean ± SD Florence Prediction Rule, mean ± SD Heart rate (resting), mean ± SD Heart rate (maximal), mean ± SD Heart rate (percentage of maximal), mean ± SD Systolic arterial pressure (baseline), mean ± SD Systolic arterial pressure (maximal), mean ± SD METs, mean ± SD Angiotensin-converting enzyme inhibitors, n (%) Calcium antagonist, n (%) Statin, n (%) Antiplatelet, n (%) Anticoagulants, n (%) β-Blockers, n (%)

59.2 ± 16.4 128 (68) 94 (50) 24 (13) 56 (30) 47 (25) 39 (21) 45 (24) 5.0 ± 3.1 2.4 ± 1.8 79 ± 16 143.5 ± 18.9 89 ± 9 127 ± 15 171 ± 24 6.8 ± 1.5 71 (38) 27 (14) 52 (28) 64 (34) 6 (3) 54 (29)

64.5 ± 12.3 12 (67) 13 (72) 2 (11) 7 (39) 4 (22) 8 (45) 3 (17) 5.6 ± 2.5 2.4 ± 1.7 80.4 ± 12.8 139.3 ± 21.4 89 ± 12.8 131.7 ± 16.9 174.7 ± 30 6.3 ± 1,4 11 (61) 5 (28) 8 (44) 11 (61) 1 (6) 7 (39)

58.7 ± 16.7 116 (68) 81 (48) 22 (13) 49 (29) 43 (25) 31 (18) 42 (25) 4.9 ± 3.1 2.4 ± 1.9 79.4 ± 16 143.9 ± 18.6 88.8 ± 8.7 126.6 ± 15 171 ± 23 6.8 ± 1.5 60 (32) 22 (13) 44 (26) 53 (31) 5 (3) 47 (28)

.076 1.000 .080 1.000 .419 1.000 .015 .570 .302 .932 .756 .389 .955 .233 .615 .152 .041 .147 .103 .017 .458 .411

Please cite this article as: Conti A, et al, Comparison of exercise electrocardiogram and exercise echocardiography in intermediate-risk chest pain patients, Am J Emerg Med (2014), http://dx.doi.org/10.1016/j.ajem.2014.09.035

A. Conti et al. / American Journal of Emergency Medicine xxx (2014) xxx–xxx

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Table 2 Univariate and multivariate analyses in patients with chest pain and negative first-line screening for coronary artery disease enrolled in the study and subjected to follow-up (n = 188) Univariate analysis

Ex-Echo Ex-ST/HF/QRS Kown cardiovascular disease Antiplatelet Hypertension Angiotensin-converting enzyme inhibitors Calcium antagonist Statin β-Blockers Anticoagulants Chest pain score ≥7 Hypercholesterolemia Mean age Systolic arterial pressure (maximal mean value) Florence Prediction Rule Percentage of maximal heart rate Heart rate (maximal mean value) Male sex Smoker Diabetes mellitus METs (maximal mean value) Familiarity for coronary artery disease

Multivariate analysis

OR

95% Confidence interval

P

OR

95% Confidence interval

P

18.98 8.63 3.59 3.47 2.86 2.88 2.59 2.29 1.67 1.94 1.43 1.57 1.03 1.01 1.01 1.00 0.99 0.93 0.844 0.841 0.79 0.61

6.29-57.22 2.40-30.99 1.31-9.83 1.27-9.45 0.98-8.35 1.06-7.82 0.84-7.97 0.85-6.17 0.61-4.52 0.21-1.04 0.48-4.28 0.58-4.29 0.99-1.06 0.99-1.03 0.78-1.32 0.95-1.06 0.96-1.01 0.33-2.61 0.26-2.70 0.18-3.91 0.57-1.11 0.17-2.21

b.001 .001 .013 .015 .056 .038 .098 .101 .320 .791 .521 .378 .153 .523 .937 .938 .323 .890 .775 .825 .176 .451

12.7 5.21

4.03-40.3 1.34-20.29

b.001 .017

In addition, areas under ROC analysis of the novel ex-ECG and ex-Echo were comparable. Several previous studies have suggested that the decrease in HF/QRS intensity precedes and is more sensitive than ST-segment changes; indeed, these studies have demonstrated the relation between decreased HF/QRS intensity and myocardial ischemia including animal models of coronary occlusion [6–8], and myocardial ischemia induced by intracoronary balloon occlusion in humans and in patients with acute ST-segment elevation myocardial infarction [11,27,28]. Usually, previous conventional techniques for ECG detection of exercise-induced myocardial ischemia have relied on identification of repolarization abnormalities manifested as ST-segment changes in the 0.05- to 100-Hz frequency band [29,30]. High-frequency QRS analysis is based on detection of specific depolarization changes caused by ischemia within the QRS complex [5]. As a result, high-frequency components of the QRS complex coming from the ischemic region are decreased. In the study of Sharir et al [10], the HF/ QRS analysis showed a cutoff for myocardial ischemia of at least 10%, derived from semiquantitative analysis of myocardial ischemia by nuclear scan imaging, used as the criterion standard of stress-induced ischemia. The cutoff value identified patients with moderate-to-severe stress induced ischemia, minimizing the inclusion of equivocal myocardial

Fig. 2. Predictive values of stress testing. Novel ex-ECG, dark-bars; ex-Echo, gray-bars. Specificity: P b .05; NS for the other comparisons.

perfusion imaging studies with artifactual defects as positive for ischemia. In this study, the HF/QRS analysis compared with exercise tolerance test analysis was more sensitive (69% vs 39%, P b .005) and more specific (86% vs 82%, P b .05) in detecting ischemia. Furthermore, Sharir et al associated a larger abnormality in HF/QRS response with a larger amount of myocardial perfusion imaging ischemia and with a poor outcome. In the present study, we considered HF/QRS analysis without any threshold for abnormality because in an emergency setting, the separation of low-risk patients, who can be safely discharged, from high-risk patients, who need admission, is mandatory irrespective of the severity of the illness. Indeed, acute chest pain can be associated with mild or severe myocardial ischemia. Thus, in order to standardize the criteria for the analysis of ST-segment changes or HF/QRS changes as myocardial ischemia, we considered that the ECG alterations need to be present in 2 or more contiguous leads.

Fig. 3. Receiver operating characteristic analysis for diagnosis of coronary stenosis of 50% or greater and adverse coronary events in low-risk chest pain patients enrolled in the study and submitted to the novel ex-ECG vs ex-Echo. Comparison of different ROC analysis on C statistic: ex-ECG vs ex-Echo, 0.167; ex-ECG vs CPS N7, 0.412; ex-Echo vs CPS N7, 0.967.

Please cite this article as: Conti A, et al, Comparison of exercise electrocardiogram and exercise echocardiography in intermediate-risk chest pain patients, Am J Emerg Med (2014), http://dx.doi.org/10.1016/j.ajem.2014.09.035

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A. Conti et al. / American Journal of Emergency Medicine xxx (2014) xxx–xxx

Table 3 ROC analysis according to the occurrence of the end point inclusive of coronary stenosis ≥50% at angiography or myocardial infarction, revascularization, and cardiac death at follow-up Sensitivity

Novel ex-ECG Ex-Echo Chest pain score ≥ 7 Exercise ST-segment analysis Ex-HF/QRS analysis

0.830 0.611 0.280 0.33 0.720

1 − Specificity

0.370 0.077 0.210 0.036 0.343

Area

SE

0.733 0.767 0.532 0.649 0.690

4.2. Impact on clinical practice of the novel ex-ECG [5]

The novel ex-ECG might aid the emergency physician to stratify chest pain patients and eventually should drive the threshold approach to clinical decision making over clinical parameters and ST-segment analysis. In fact, the results of the present study suggest that the novel ex-ECG is a valuable diagnostic tool comparable with the validated execho in intermediate-risk chest pain patients presenting themselves to primary or secondary care hospitals. Patients with negative test results could be discharged safely; other testing could add very little in terms of better health. These data support the “less is more” philosophy part of the Choosing Wisely program, sponsored by the American Board of Internal Medicine Foundation [31–33]. Additional testing like CTA might be performed in a tertiary care hospital only in a few patients, when required by clinical judgment, due to costs, requested specific expertise, and time-sensitive availability [1,34–37]. 4.3. Limitations and strengths of the study Notwithstanding the large series of patients enrolled in the present study, limitations are represented by the lack of randomization to diagnostic strategy; the lack of analysis of costs of the 2 diagnostic strategies; the need of validation in other centres, because patients enrolled in the present study derive from patients presenting only to our hospital; and, finally, the high proportion of patients not enrolled due to poor echoacoustic window and inability of exercise. Conversely, the strengths of the present study are represented by the detection of sensitivity and specificity of the novel ex-ECG within the range reported in previous studies; the novel ex-ECG might be widely applicable by emergency physicians with cardiology on call, saving time and cost for diagnosis.

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13] [14] [15]

[16]

[17]

5. Conclusions [18]

The novel ex-ECG including the computer-assisted stress testing high-frequency QRS analysis associated with the conventional STsegment analysis might aid the emergency physicians to stratify intermediate-risk chest pain patients. The novel ex-ECG demonstrated comparable sensitivity and negative predictive value when compared with the validated ex-Echo, leading to future applications in acute cardiac care. This novel test shows promise but needs additional studies before it can be recommended as a replacement for current techniques.

[19]

[20]

[21]

[22]

References [1] Sechtem U, Achenbach S, Andreotti F, Budaj A, Bugiardini R, Crea F, et al. 2013 ESC guidelines on the management of stable coronary artery disease. Eur Heart J 2013; 34(38):2949–3003. [2] Pauker SG, Kassirer JP. The threshold approach to clinical decision making. N Engl J Med 1980;302(20):1109–17. [3] Gibbons RJ, Balady GJ, Bricker JT, Chaitman BR, Fletcher GF, Froelicher VF, et al. ACC/ AHA 2002 guideline update for exercise testing: summary article—a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Circulation 2002;106(14):1883–92. [4] Amsterdam EA, Kirk JD, Bluemke DA, Diercks D, Farkouh ME, Garvey JL, et al. Testing of low-risk patients presenting to the emergency department with chest pain a

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0.057 0.071 0.073 0.079 0.065

Significance

.001 .000 .652 .038 .008

95% Confidence interval Lower limit

Higher limit

0.620 0.630 0.390 0.490 0.560

0.850 0.910 0.680 0.800 0.820

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Please cite this article as: Conti A, et al, Comparison of exercise electrocardiogram and exercise echocardiography in intermediate-risk chest pain patients, Am J Emerg Med (2014), http://dx.doi.org/10.1016/j.ajem.2014.09.035

Comparison of exercise electrocardiogram and exercise echocardiography in intermediate-risk chest pain patients.

The novel exercise computer-assisted high-frequency QRS analysis (HF/QRS) has demonstrated improved sensitivity and specificity over the conventional ...
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