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Lau J, Ioannidis JPA, Balk E, et al. Evaluation of Technologies for Identifying Acute Cardiac Ischemia in Emergency Departments. Rockville (MD): Agency for Healthcare Research and Quality (US); 2001 May. (Evidence Reports/Technology Assessments, No. 26.)
This publication is provided for historical reference only and the information may be out of date.
Evaluation of Technologies for Identifying Acute Cardiac Ischemia in Emergency Departments.
Show detailsThe results presented in Chapter 3 are based on the screening of 6,667 MEDLINE titles and 407 full articles, 105 of which are analyzed in this report. About one-third of the 6,667 articles were published since 1994, and 45 of the 105 articles we used were published between 1994 and 1998. These numbers indicate a large increase in research activities on this topic during the past 5 years compared with the previous 27 years.
A diverse array of technologies with varying degrees of diagnostic accuracy and costs is available for use in general or selected patient populations to diagnose ACI in the ED. These technologies include ECG-based tests, blood tests of biomarkers, imaging studies, stress testing, and computer-based decision aids; the technologies detect various facets and manifestation of ACI. The direct costs of these technologies range from being almost free (ACI-TIPI and the Goldman chest pain protocol) to $1,000 or more (sestamibi perfusion imaging). The evidence we reviewed indicates that none of the current technologies distinguish all patients with ACI from those without. Although the optimal diagnostic approach may be some combination of these tests that has yet to be evaluated, several technologies come close to offering the desired tradeoff between costs and effectiveness.
Table 51 summarizes the results of all the diagnostic performance studies evaluated, and Table 52 summarizes the clinical impact studies.
Table
Table 51. Summary of test performance studies of diagnostic technologies for acute cardiac ischemia in emergency departments.
Table
Table 52. Summary of clinical impact studies of diagnostic technologies for acute cardiac ischemia in emergency departments.
General Observations on the Studies Analyzed
In addition to the conclusions described in this chapter, we believe that the data support the following observations:
- Research on the diagnosis of ACI in the ED is characterized by great heterogeneity in the studies as a result of the large number of variables that can be studied. This heterogeneity has resulted in fragmented evidence that is not easily synthesized into a coherent whole.
- There are a limited number of studies, both on technologies' diagnostic performance and in their clinical impact, on patients with ACI. Most studies evaluated only patients with AMI.
- The methodological quality of the diagnostic performance studies on this topic varies widely but, in general, needs to be greatly improved. Most of the evidence for diagnostic performance is based on studies that were given a "B" or "C" methodological quality rating.
- The number of new studies published in the past 5 years on the clinical impact of these technologies is disappointingly small.
- Some technologies (e.g., echocardiography, sestamibi perfusion imaging, exercise ECG) remain underevaluated.
- The prevalence of ACI varies widely among the studies, even for apparently similar patient populations defined by the inclusion criteria. This heterogeneity raises the question of the applicability of the study results to other settings.
- Little work has been done on the value of sequential testing or on test combinations.
We also found several instances of multiple reports of the same study. Sometimes these reports were updates of preliminary reports and contained data on additional patients; however, this overlap made it difficult to distinguish new information from old, thus introducing bias of either overcounting or undercounting depending on the decision to include or exclude the overlapping studies. Sometimes these studies did provide useful, complementary information.
Observations on the Prevalence of Acute Cardiac Ischemia
To help interpret the results, we examined the prevalence of ACI and AMI in the four population categories. About one-half of the studies analyzed patients in population category II, and about one-third of the studies analyzed patients in category III. The prevalence of AMI across studies of patients in the same population categories and in similar settings varied widely, and there was little indication that similar inclusion and exclusion criteria resulted in similar ACI and AMI prevalence. The lack of association between the population categories defined by the inclusion criteria and the prevalence of ACI raises the question of whether the inclusion criteria used in current studies are sufficiently refined to allow their results to be applied in other settings.
Despite this lack of association, overall, studies that included all patients with chest pain (population category II) did how a higher prevalence of AMI than did studies that included all patients with any symptom suggestive of ACI (population category I) or studies that excluded patients with diagnostic ECGs (population category III). In addition, although differences in AMI prevalence in studies in different settings were not statistically significant, studies that analyzed only ED patients admitted to either the hospital or to the CCU did show a higher prevalence of AMI than those that included all ED patients and therefore may have truly represented different populations.
Conclusions About the Diagnostic Technologies
Prehospital 12-Lead Electrocardiography
The diagnostic accuracy of prehospital 12-lead ECG for AMI and ACI, as expected, was similar to that of the standard 12-lead ECG, which is the standard of care in the management of patients suspected of having ACI. The accumulated evidence is substantial in both the total sample size and quality, and the data were gathered from patient populations with few exclusion criteria.
The evidence shows that obtaining a prehospital 12-lead ECG does not prolong time in the field or delay transport to the ED. In addition, prehospital ECG-guided thrombolytic therapy can be administered 45 minutes to 1 hour earlier than hospital-based thrombolysis. Prehospital thrombolysis has a modest but significant impact on early mortality. Approximately 60 patients would need to be administered prehospital thrombolysis to save one additional life, in the short term, compared with hospital thrombolysis. Short-term, beneficial effects of thrombolysis on the left ventricular ejection fraction have not been reported in randomized trials. The long-term survival benefits of prehospital thrombolysis remain uncertain.
Continuous/Serial 12-Lead ECG
Two studies evaluated the test performance of continuous/serial 12-lead ECG in the ED, but there was no clinical impact study. The two studies were quite dissimilar. One by Gibler, Runyon, Levy, et al. (1995) included a large retrospective population of 1,010 participating in a 9-hour protocol. The "serial ECG" consisted of a 20-second interval between readings. The second study by Hedges, Young, Henkel, et al. (1992) included patients from a veterans' hospital in which two ECGs were taken 4 hours apart. The prevalences of ACI in these studies were very different (4 and 40 percent, respectively) given the low-risk populations. The sensitivity for ACI was low (21 and 25 percent, respectively), and the specificity was high (92 and 99 percent, respectively). With the limitations and the varied source of the data, a conclusion about the utility of this technology cannot be drawn.
Nonstandard Lead ECG
The data on the diagnostic performance of nonstandard lead ECG from the four studies reported varied too much to draw any conclusion. The studies used 15, 18, 22, and 24 leads and were conducted with selected patients for admission. The prevalence was reflective of this selective population: It ranged between 22 and 65 percent for AMI. There were no clinical impact studies on nonstandard ECGs.
Exercise Stress ECG
The data on the diagnostic performance of exercise stress testing to detect ACI in the ED were limited to only two studies, both published after the earlier NHAAP report. The overall data included a small sample size of a low-risk population. Although the diagnostic performance was encouraging, it would be premature to make conclusions regarding this technology until additional high-quality studies are conducted.
There were also limited data on the clinical impact of exercise stress testing for ACI, with one of the three studies published since the report by the Working Group. The first two studies, Tsakonis, Roth, Psaty, et al. (1991) and Kerns, Shaub, and Fontanarosa (1993), had no cardiac events and included very small sample sizes, 28 and 35, respectively. Because these studies reported on a total of only 272 subjects and were of low methodological quality, the clinical impact of this technology is unclear.
Biomarkers
Creatine Kinase (CK), Single and Serial Measurements
The amount of evidence on CK as a single test administered at presentation to patients in the ED is large. As shown in Table 51, the evidence suggests that the sensitivity of a single CK reading for AMI is low (36 percent), and the specificity is modest (88 percent). Limited evidence suggests that the sensitivity of the test depends on the duration of the patient's symptoms; sensitivity increases with longer symptom duration. Test performance across studies did not appear to vary by type of hospital, inclusion criteria, AMI prevalence, or test threshold.
Only two studies have evaluated serial CK testing. Both used broad inclusion criteria but enrolled populations in which the prevalence of AMI was moderate to high. Test sensitivity was high (95 to 99 percent) in serial tests performed over about 15 hours after presentation to the ED (or from the onset of symptoms), but was only modest (69 percent) in the one study that drew serial samples for 4 hours. Test specificity was modest in both studies (68 and 84 percent).
As a single test, CK is insensitive and only modestly specific for AMI. Serial testing appears to have a higher sensitivity, although the specificity remains modest. However, the evidence is insufficient to evaluate serial CK measurements over a short time. Because high serum CK levels represent infarcted myocardium, CK has not been evaluated for diagnosing ACI in the ED. There were no clinical impact studies for CK.
Creatine Kinase Subunit (CK-MB), Single and Serial Measurements
As is the case with CK, the total sample size and number of studies on a single CK-MB measurement at presentation to the ED are large. The evidence suggests that the sensitivity of single CK-MB for AMI is low (44 percent), although specificity is high (96 percent). Studies reported a broad range of sensitivity for diagnosing AMI. Again, as is the case for CK, limited evidence suggested that the sensitivity of CK-MB depends on the duration of the patient's symptoms; sensitivity increases with longer symptom duration. In general, studies reported a narrow range (92 percent to 99 percent) of test specificity. Test performance across studies did not appear to vary by type of hospital, inclusion criteria, AMI prevalence, or test threshold.
The total sample size and number of studies of serial tests for CK-MB in the ED setting are large. Overall, serial testing had a modest sensitivity (87 percent) and a high specificity (96 percent) for AMI. However, test sensitivity was strongly related to the timing of serial testing. All studies that performed serial testing for at least 4 hours after presentation to the ED (or until at least 8 hours after symptom onset) found test sensitivity to be greater than 90 percent. Conversely, all studies that performed serial testing to at most 3 hours found test sensitivity to be lower than 90 percent. The pooled sensitivity for serial testing to at least 4 hours was 96 percent; the pooled sensitivity for serial testing until 3 hours was only 81 percent. In general, test specificity was in a narrow range across studies and was above 90 percent.
CK-MB as a single test was only modestly sensitive and specific for AMI; however, serial testing performed over 4 to 9 hours was highly sensitive and highly specific. Because serum CK-MB levels represent infarcted myocardium, CK-MB has not been tested for diagnosing ACI in the ED. There were no clinical impact studies for CK-MB.
Troponin T and Troponin I
The evidence for the diagnostic performance of troponin T is substantial for diagnosing AMI but rather limited for diagnosing ACI. Data for troponin I are limited, but its performance was similar to that of troponin T. The sensitivity of presentation troponin T for diagnosing AMI in the ED was poor, but it improved substantially if serial measurements were obtained for up to 6 hours after ED presentation. Most likely, the sensitivity was better for patients who have had symptoms for longer periods of time. The specificity of troponin T for AMI was in the range of 90 percent.
Myoglobin
The diagnostic performance of myoglobin has been well studied for diagnosing AMI, but not for diagnosing ACI. The performance of myoglobin was similar to that of CK-MB, except that serial testing may have provided adequately high sensitivity earlier. The sensitivity of myoglobin for diagnosing AMI in the ED was poor (49 percent) when a single initial measurement was obtained, but sensitivity improved greatly if a second measurement was obtained 2 to 4 hours after the first one (>86 percent). However, the sensitivity for patients only recently symptomatic was poor, and a second measurement in 2 to 4 hours may still not have been sufficiently sensitive to be useful. Specificity was very good, but not excellent. Its deviation from excellence in the various reports probably depended on the extent to which other reasons for elevated myoglobin were excluded a priori. There is limited evidence to suggest that the failure of myoglobin level to increase over 1 to 2 hours was excellent at excluding AMI (specificity >94 percent).
Other Biomarkers
Studies on P-selectin and malondialdehyde-modified low-density lipoprotein are just beginning to appear. There was only one ED study of P-selectin that reported low sensitivity and low specificity for AMI.
Combination CK-MB and Myoglobin
The only combination of biomarkers to diagnose AMI that has been reported is CK-MB and myoglobin, and this in only three studies. In addition, it appears that the decision to analyze this combination was made post hoc, and thus the findings may have overestimated true test performance (as studies with poor test performance may have been less likely to report their finding). That said, combination CK-MB and myoglobin at ED presentation (where a positive test was defined as either CK-MB or myoglobin being elevated) had good test performance, with both a high sensitivity (83 percent), though poorer specificity (82 percent), as compared with presentation CK-MB or myoglobin alone. Serial combination CK-MB and myoglobin (where a positive test was defined as any of the four serum samples being elevated) performed similarly to the individual serial biomarkers, although sensitivity may be higher (100 percent).
Echocardiography
The total sample size and the number of the studies evaluating echocardiography for the diagnosis of ACI are small. Limited evidence suggests that resting echocardiography has high sensitivity (93 percent) although only modest specificity (66 percent) for AMI. The availability of previous echocardiograms for comparison may improve the specificity (Mohler, Ryan, Segar, et al., 1998). But even if this improved specificity is verified with additional studies, the need for previous echocardiography would limit its applicability in the general ED setting. In addition, the data pertain mostly to patients with normal or nondiagnostic ECGs. The data for stress dobutamine echocardiography are even more limited, but the one study suggests that it may be the next diagnostic step for patients with a negative resting echocardiogram, normal ECGs, and normal enzyme levels. There was no clinical impact study for this technology.
Technetium-99m Sestamibi Myocardial Perfusion Imaging
Data on the diagnostic accuracy of resting Tc-99m sestamibi imaging in the ED are limited, and there are still no data on its clinical impact. The test has been used in selected patient populations that generally have a low-to-moderate risk of ACI, no history of myocardial infarction, and a presenting ECG nondiagnostic for ACI. Thus, the generalizability of the current evidence is limited, and the test should be reserved for these circumscribed populations. In these patients, the test had excellent sensitivity for AMI, and very good, but not perfect, sensitivity for coronary disease in general. Specificity was modest for AMI, and although it may be a little better for ACI, it was still far from excellent.
Acute Cardiac Ischemia Time-Insensitive Predictive Instrument (ACI-TIPI)
The ACI-TIPI computes a 0-100 percent probability that a given patient has ACI (i.e., either acute myocardial infarction or unstable angina pectoris). Applicable to any ED patient presenting with any symptom suggestive of ACI, it is based on a logistic regression equation that uses presenting symptoms and ECG variables. Originally in a handheld calculator form, it is now incorporated into conventional electrocardiographs so that the patient's ACI-TIPI probability is printed with the standard ECG header text. In large controlled interventional trials in a wide range of hospitals, its use by ED physicians has been shown to reduce unnecessary admissions of patients without ACI and patients with stable (as opposed to unstable) angina, while not reducing appropriate hospitalization for patients with ACI. It has also been shown to help the triage speed and accuracy of less-trained and less-supervised residents. The wider dissemination and use of ACI-TIPI could result in significant positive impact on the triage of ACI patients in the ED.
Goldman Chest Pain Protocol
The Goldman chest pain protocol is based on a computer-derived model using recursive partitioning analysis to predict myocardial infarction in patients with chest pain. It has good sensitivity (about 90 percent) for AMI, but it was not developed to detect UAP as well. In a clinical impact study of "low-intensity, nonintrusive intervention" performed at a teaching hospital ED, no differences in hospitalization rate, length of stay, or estimated costs were demonstrated between the experimental group, which used the protocol, and the control group.
Other Computer-Based Decision Aids
Several investigators reported various computer-based decision aids to diagnose AMI. The artificial neural network (Baxt and Skora, 1996) was found to have high sensitivity and high specificity for AMI in a prospective study, but the clinical impact was not demonstrated.
Decision and Cost-Effectiveness Analysis
Some technologies for diagnosing ACI in the ED are more accurate and more expensive than others. We developed a cost-effectiveness model to evaluate the tradeoff between the costs of using a technology for the diagnosis of ED patients with ACI and its accuracy.
Decision and cost-effectiveness analyses were performed for 17 technologies and 4 combinations of technologies that were evaluated in the literature and this report. The cost analysis is from the payers' perspective (e.g., health insurance companies); patient outcomes are either appropriate triage or 30-day survival of patients with ACI.
As not all technologies can be applied to all patients in the ED (such as stress ECG), two different ED populations were used for the analysis: a general population model (population category I) with an AMI prevalence of 8 percent, and a subgroup model, in which high-risk patients are excluded (AMI prevalence of 6 percent). Stress tests, sestamibi imaging, and serial and continuous ECG were evaluated only in the subgroup population.
As expected, technologies with the best diagnostic accuracy for AMI and UAP had the highest values for appropriate triage for patients with ACI. Technologies that are more effective (greater number of patients with ACI appropriately triaged) tended to have higher total costs, with the exception of ACI-TIPI. The biomarkers were least costly and had the lowest values for appropriate triage. Algorithms, combination technologies, and echocardiography were the next most effective technologies, in that order. Sestamibi imaging and exercise ECG were more expensive than other technologies, but had excellent diagnostic performance for patients with ACI. Although the diagnostic performance of ACI-TIPI is hard to assess, its use did not decrease appropriate triage for patients with ACI; a large clinical trial showed that 97 percent of patients with ACI were appropriately triaged when the instrument was made available to ED physicians.
Based on data using only the diagnostic performance data of technologies, the combination technology of troponin T-echocardiography was the most cost-effective of all technologies applicable to the general population model. If results from clinical impact studies are incorporated, ACI-TIPI was the most cost-effective because of its very high triage accuracy and low cost.
The incremental cost-effectiveness of troponin T-echocardiography is about $7,670 per additional appropriate triage for a patient with ACI compared with the cost of serial or combination biomarkers.
The incremental cost-effectiveness of troponin T-echocardiography compared with that of the artificial neural network was approximately $10,568. The greater incremental cost-effectiveness reflected the smaller difference in triage accuracy between the artificial neural network and troponin T-echocardiography compared with that between the biomarkers and troponin T-echocardiography. Given the economic ramifications and the effects on the patient of a missed ACI diagnosis, this incremental cost-effectiveness for troponin T-echocardiography is minimal.
Because the estimates for UAP detection were based on sparse data, we evaluated the triage accuracy and cost-effectiveness of technologies for appropriate triage for patients with AMI only. In general, the relative cost-effective rankings for AMI triage accuracy were similar to those for patients with ACI. There were a few but important differences in triage accuracy for patients with AMI: (1) the Goldman protocol improved significantly, (2) serial CK-MB improved slightly, and (3) the combination troponin T-echocardiography was slightly better than ACI-TIPI (a difference of one patient with AMI appropriately triaged).
The combination troponin T-echocardiography was the most cost-effective, followed by the artificial neural network. The incremental cost-effectiveness between these two technologies was much larger than in the general ACI model: approximately $137,000 per additional appropriately triaged patient with AMI.
Sensitivity analyses, in which the prevalence of ACI was increased from 10 to 90 percent, does not change the relative cost-effectiveness of the technologies. As prevalence increased, the differences in cost-effectiveness among the technologies became smaller because costs increased less steeply than effectiveness values. At a prevalence as great as 90 percent, ACI-TIPI retained its dominant cost-effectiveness, followed by troponin T-echocardiography and artificial neural network.
In the subgroup model, ACI-TIPI was again the most cost-effective technology if data from clinical impact studies were incorporated. Sestamibi stress imaging had the best diagnostic performance (detected 82 percent of patients with ACI), followed by sestamibi rest scanning and exercise ECG. The per ED patient costs for these technologies, at over $2,700, were around $400 more than those for ACI-TIPI. The incremental cost-effectiveness between stress sestamibi imaging and the next cost-effective technology, the combination troponin T-echocardiography, was $12,757. As stress sestamibi imaging may result in the appropriate triage of 37 additional patients with ACI (per 1,000 ED patients) compared with troponin T-echocardiography, it appears to be a very cost-effective technology.
If data from the ACI-TIPI trial were used, the incremental cost-effectiveness of using ACI-TIPI compared with troponin T-echocardiography was only $1,502 per additional appropriate triage for a patient with ACI, a truly negligible increase for improved triage accuracy.
In the AMI only triage model, troponin T-echocardiography was the most cost-effective: it was less expensive than all the imaging technologies as well as ACI-TIPI and appropriately triaged nearly 99 percent of patients with AMI. Exercise ECG and stress sestamibi imaging also had 99 percent sensitivity for patients with AMI; however, the per ED patient costs for these two technologies is about $500 more than those for troponin T-echocardiography. The triage accuracy and cost for ACI-TIPI was nearly identical to those for troponin T-echocardiography. When the analysis was performed with the cost of ACI-TIPI at $0, the cost-effectiveness of ACI-TIPI and the combination was essentially equivalent.
The results of the decision and cost-effectiveness analysis should not be used as a definitive analysis of technology triage accuracy, as data on the actual effect on triage are lacking for most of the technologies. Furthermore, the values for sensitivity for UAP were estimates based on sparse data, which added to the uncertainty of the model. The decision analysis is also not meant to be used for clinical recommendations for individual patients, as pretest likelihoods are not explicitly modeled. Rather, these results should be used as an aid in decisionmaking and in understanding the factors that are involved in triage of patients with ACI in the ED. Prospective trials on the effect of technologies on actual ED patient triage are required before definitive conclusions can be made.
- Conclusions - Evaluation of Technologies for Identifying Acute Cardiac Ischemia ...Conclusions - Evaluation of Technologies for Identifying Acute Cardiac Ischemia in Emergency Departments
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