Cardiovascular Section, Department of Medicine, University of OklahomaHealth Science Center, Oklahoma City, Oklahoma; Duke Clinical ResearchInstitute, Duke University Medical Center, Durham, North Carolina; and

Department of Medicine, Brigham and Women’s Hospital, Harvard MedicalSchool, Boston, Massachusetts.

(Am J Cardiol 2014;113:256e261)

INTRODUCTION

• Risk stratification remains central to implement appropriate therapeutic measures for patients with NSTEMI.

• The ECG provides rapid risk assessment for

patients presenting with chest pain that permits their allocation to appropriate management algorithms to improve the outcomes.

• Patients diagnosed with NSTEMI constitute a heterogeneous group with several variations of ECG findings at presentation, including ST-segment depression, T-wave inversions, transient ST-segment elevation, or no ischemic changes.

• From previous studies, ST-segment depression has been

considered to be a high-risk ECG finding in patients with NSTEMI with an increased risk of early and long-term cardiovascular events, who often benefit from early invasive management.

• However, the clinical characteristics, outcomes, and treatment of patients presenting with transient ST-segment elevation have been less well defined.

• It has been suggested that intensive medical therapy and early

angiography are acceptable treatment options for these patients.

• Limited data are available on the characteristics and treatment of patients with NSTEMI presenting with no ischemic changes.

• A comparison between these 4 ECG subgroups in NSTEMI has not been previously performed, especially in contemporary practice.

• Such a comparison would help better characterize, and give additional insight to, the appropriate treatment of patients with NSTEMI according to the ECG findings.

• Thus, we performed an analysis of the National Cardiovascular Data

Registry Acute Coronary Treatment and Intervention Outcomes Network Registry Get With The Guidelines (ACTION Registry-GWTG) in patients with NSTEMI according to the presenting ECG findings.

METHODS

• The National Cardiovascular Data Registry’s ACTION Registry-GWTG is a voluntary registry that receives data on consecutive patients with ST-segment elevation myocardial infarction (STEMI) and NSTEMI that began enrollment on January 1, 2007.

• Patients were eligible for inclusion in the ACTION Registry-GWTG if they had presented within 24 hours from the onset of ischemic symptoms and received a primary diagnosis of NSTEMI or STEMI.

• A total of 349,557 patients were identified in the ACTION Registry GWTG from 664 sites from January 2007 to September 2011.

• Patients presenting with STEMI (n = 136,940), patients with partial data (n = 20,786), patients arriving to sites without PCI capabilities (n = 8,328), patients transferred to other facilities (n = 6,788), and patients with missing ECG findings (n = 1,159) were excluded.

• Included in the present analysis were 175,556 patients from 485 sites

• The presenting ECG findings were documented within 24 hours of arrival to the reporting hospital.

• The 4 subgroups constituted the NSTEMI group in the ACTION Registry GWTG

data form: ST-segment depression, T-wave inversions, transient ST-segment elevation, and no ischemic changes.

• ST segment depression was defined as new, or presumed new, horizontal or

downsloping ST-segment depression ≥ 0.5mV in 2 contiguous leads below the isoelectric line on the electrocardiogram.

• T-wave inversion was defined as new, or presumed new, T-wave inversion of ≥ 0.1 mV in 2 contiguous leads with a prominent R wave or R/S ratio >1 within the first 24 hours of presentation.

• Transient ST-segment elevation was defined as new, or presumed new, ST-

segment elevation at the J-point in 2 contiguous ECG leads with the cutoff points of ≥ 0.2mV in men or ≥ 0.15mV in women in leads V2 to V3 and/ or ≥ 0.1 mV in other leads, and lasting <20 minutes, within the first 24 hours of presentation.

• The ECG was considered to have no ischemic changes if the first ECG had not revealed ST-segment depression, transient ST-segment elevation, or T-wave inversion.

• If a patient had simultaneous ECG findings, grouping was done such that if the ECG showed transient ST-segment elevation and other findings, it was assigned to the transient ST-segment elevation group.

• If the ECG revealed ST-segment depression and T-wave inversion (but not

transient ST-segment elevation), it was assigned to the ST-segment depression group.

• Of the 1,844 patients categorized as having transient ST-segment

elevation, 335 also had ST-segment depression, 215 also had T-wave inversion, and 80 also had both ST-segment depression and T-wave inversion.

• Of the 10,743 patients categorized as having ST-segment depression, 1,924 also had T-wave inversion.

• The demographics, co-morbidities, and in-hospital procedures and mortality were compared across the 4 ECG categories.

• Continuous variables are presented as the median and interquartile range and categorical variables as percentages.

• All continuous variables were compared using the Kruskal- Wallis tests, and all categorical variables were compared using chi-square tests.

• To estimate the relative risks of the ECG findings on in-hospital mortality, we used the logistic generalized estimating equation method with the exchangeable working correlation matrix to account for within-hospital clustering, because patients at the same hospital are more likely to have similar outcomes relative to patients at other hospitals (i.e., within-center correlation for outcome).

• Using the no ischemic changes group as the reference, odds ratios for mortality were calculated for the other 3 groups.

• The model included covariates from the validated ACTION Registry-GWTG in-hospital mortality model.

• Also, to evaluate the relation between peak troponin and in-hospital mortality, we categorized the peak troponin ratio (greatest recorded troponin value within the first 24 hours/local laboratory troponin upper limit of normal value) into quartiles

• Furthermore, linear trends of in-hospital mortality across the quartiles and the interaction between the ECG subgroups and the quartiles were tested using logistic regression analysis.

• Patients who died within 24 hours (n=1,166) and patients without a peak troponin level recorded (n = 7,472; i.e., only baseline troponin values were recorded; thus, the peak value could not be ascertained) were excluded from the present analysis.

• All analyses were performed using Statistical Analysis Systems software, version 9.2 (SAS Institute, Cary, NC)

RESULTS

• A total of 175,556 patients were entered into the present analysis from 485 sites from January 2007 to september 2011 and grouped according to the presenting ECG findings:

• ST-segment depression (n = 40,146, 22.9%), • T-wave inversion (n = 24,627, 14%), • Transient ST-segment elevation (n = 5,050,

2.9%), and • No ischemic changes (n = 105,733, 60.2%).

Discussion

• The present analysis of the ACTION Registry-GWTG has provided important insight regarding the clinical characteristics, in-hospital treatment, and outcomes of patients presenting with NSTEMI when stratified by the presenting ECG findings.

• The present study represents the largest and most recent

evaluation of patients with NSTEMI according to the presenting ECG findings from hospitals throughout the United States.

• In our study, the most common finding on the presenting ECG for patients with NSTEMI was no ischemic changes (60.2%) followed by ST-segment depression (22.9%), T-wave inversion (14%), and transient ST-segment elevation (2.9%).

• Of the 4 subgroups analyzed, patients with ST-segment depression found on the ECG were the oldest, had the highest incidence of co-morbidities, and the highest in-hospital mortality.

• High-risk angiographic findings, including left main, proximal left anterior descending, and 3-vessel CAD also had the highest prevalence in this group. Also, these patients underwent coronary artery bypass grafting most often.

• These findings complement previous data showing that

patients presenting with ST-segment depression constitute the highest risk group among patients with NSTEMI.

• Savonitto et al reported a higher short-term incidence of death or MI in patients with ACS presenting with ST-segment depression compared with those presenting with T-wave inversion.

• In the present analysis, patients with ST-segment depression had remarkably higher in-hospital mortality compared with those with no ischemic changes. Patients presenting with ST-segment depression have also been shown to have worse cardiovascular outcomes in long-term analyses.

• Despite being a high-risk population, these patients were not the group that underwent cardiac catheterization most frequently.

• These findings corroborate data from previous analyses of patients with NSTEMI showing an inverse relation with the risk status of the patient and the rate of coronary angiography, despite data showing that an invasive strategy is of benefit.

• The current practice patterns in this high-risk group probably

represent an opportunity for improvement.

• Transient ST-segment elevation was the least frequent finding on the ECG (2.9%), and these patients constituted a distinct group of younger patients with fewer co-morbidities.

• Additionally, these patients were treated more aggressively, with a higher proportion undergoing coronary angiography and revascularization.

• In everyday practice, these patients pose a therapeutic

challenge, because the optimal management has been less well-defined and might be judged as high-risk acute coronary syndrome.

• It is likely that this ECG finding has been perceived to be a high-risk feature similar to STEMI and thus leading to a more aggressive therapeutic approach in this patient subgroup.

• In their prospective observational study, Meisel et al reported an incidence of such patients of 15.1%, with better clinical outcomes when these patients underwent reperfusion therapy compared with patients presenting with persistent STEMI.

• Similar prognostic implications were observed in the present analysis, although with a much lower prevalence of patients with transient ST-segment elevation.

• In their comparison of patients with ACS with transient ST-segment depression and those with transient ST-segment elevation who underwent continuous ECG monitoring, Drew et al reported that transient ST-segment elevation occurred almost as frequently as transient ST-segment depression.

• They also found SVD to be significantly (p = 0.0007) more frequent in the transient ST-segment elevation group (46%) compared with the transient ST-segment depression group (22%).

• Meisel et al found a frequency of Single Vessel CAD of 60% in patients with transient ST-segment elevation.

• Our study revealed a higher frequency of Single Vessel CAD in patients with transient ST-segment elevation (33.4%) compared with the other ECG subgroups.

• The 2 other groups, the T-wave inversion group and no ischemic findings group, seemed to have an intermediate burden of co-morbidities, in-hospital cardiovascular events, and angiographic findings.

• Our study showed that those with no ischemic changes constituted most (60.2%) of the patients with NSTEMI.

• Also, a lower proportion of those with no ischemic changes underwent diagnostic coronary angiography within 24 hours compared with the other groups. Similarly, a lower proportion of these patients underwent percutaneous coronary intervention or coronary artery bypass grafting compared with the other groups.

• Although the ACC /AHA guidelines for the treatment of patients with NSTEMI have suggested that the signs and symptoms of ACS in patients presenting with ST-segment deviations and/or T-wave inversion (combined with other clinical and objective findings) have a greater likelihood of being secondary to CAD and a lower likelihood for patients presenting with no ischemic changes, our study showed that compared with no ischemic changes.

• Patients with NSTEMI presenting with T-wave inversion had the lowest adjusted in-hospital mortality using the ACTION Registry-GWTG in-hospital mortality model (odds ratio 0.91, 95% confidence interval 0.83 to 0.99; p ¼ 0.026)

• The prognostic significance of troponin in patients with acute coronary syndrome is well known, and a recent analysis of the ACTION Registry-GWTG has established that the peak troponin level possesses independent prognostic implications.

• When analyzed in the present study, the quartile of peak troponin levels correlated well with overall mortality and with mortality across all 4 ECG subgroups.

• The present analysis represents observational data that in themselves have inherent limitations.

• First, the ECG results reported by the sites were not confirmed by a core laboratory.

• However, these results reflect routine practice in which ECG are interpreted by the treating physician without confirmation by a core laboratory.

• Other limitations include the lack of details on the findings of the ECGs performed after the initial ECG limited details on the angiographic findings, and limited details on nonfatal ischemic outcomes occurring during the hospitalization.

CONCLUSION• The clinical and angiographic characteristics and

treatment and outcomes of patients with NSTEMI differed substantially according to the presenting ECG findings.

• Patients with ST-segment depression have a greater burden of co-morbidities and coronary atherosclerosis and have a greater risk of adjusted in-hospital mortality compared with the other groups.

• These findings highlight the importance of integrating the

presenting ECG findings into the risk stratification algorithm for patients with NSTEMI.