a Rabin Medical Center, Petah Tikva, Israel
b Neufeld Cardiac Research Institute, Tel Hashomer, Israel
c Hôpital Européen Georges Pompidou, Paris, France
d University Hospital Jean-Minjoz, Besancon, France
* Correspondence to: David Hasdai, MD. Department of Cardiology, Rabin Medical Center, 39 Jabotinsky St. Petah Tikva, Israel 49100. Tel: 972-3-9377130. Fax: 972-3-9249850
E-mail address: dhasdai{at}post.tau.ac.il
Received 22 November 2002; revised 4 March 2003; accepted 12 March 2003
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Abstract |
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Methods and results The Euro Heart Survey of Acute Coronary Syndromes (ACS) prospectively surveyed 10484 patients in 103 hospitals across 25 European and Mediterranean basin countries during 4 September 2000 to 15 May 2001. We evaluated the use of cardiac troponin assays and whether the diagnosis of unstable angina (UA) or AMI was in accordance with the results of biomarker assays (cardiac troponins, CK-MB mass, CK-MB%, or CK). Troponin assays were used in 6036 (63.3%) of the 9538 patients with available biomarker levels; of whom elevated troponin levels were recorded in 648 of 2307 (28.1%) patients with UA and in 2957 of 3729 (79.3%) patients with AMI. Of the 8871 patients with available creatine kinase values, levels above the upper limit of normal were recorded in 848 of 3625 (23.4%) patients with UA and in 3948 of 5246 (75.3%) patients with AMI.
Conclusions Cardiac troponin assays are still not universally available for the evaluation of ACS patients. A substantial proportion of ACS patients receive a diagnosis of UA or AMI, irrespective of the result of biomarker assays, indicating that the redefinition of AMI has not yet been universally adopted, and that additional efforts are warranted to ensure its appropriate implementation.
Key Words: Acute myocardial infarction Acute coronarysyndrome Diagnosis Biomarker Troponin Creatine kinase
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1. Introduction |
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The joint committee redefining AMI emphasized that efforts should be exerted to examine whether the measures generating the new criteria, namely the cardiac troponin assays, are widespread available and applied in a standard fashion.1Moreover, the committee recommended an examination of its application over time.
The Euro Heart Survey of Acute CoronarySyndromes (Euro Heart Survey ACS) was a prospective survey of patients admitted due to an ACS in 103 hospitals across 25 countries in Europe and the Mediterranean basin.2The enrolment period was from 4 September 2000. Thus, this survey offers a unique opportunity to examine the application of the new definition of AMI across this broad region.
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2. Methods |
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All patients with suspected ACS, screened at the emergency room, chest pain units, catheterization laboratory, or otherwise were registered on a screening log, but they were not enrolled until the diagnosis of ACS was confirmed. Patients who had been in another hospital for a short (<12h) observation period and were transferred for diagnosis and management were also registered, and information from the referring hospital was sought. However, patients who were referred only for a specific treatment (i.e., cardiac catheterisation or coronary bypass surgery) were not included. The full case report form was filled out for patients with a discharge diagnosis of unstable angina or AMI. We recorded the discharge diagnosis made by the attending physicians based on the following categories: unstable angina, non-Q-wave AMI, and Q-wave AMI. Our analysis is based on the diagnosis made by the attending physicians, which at times may have been inaccurate. Indeed, this is the focus of the current analysis.
For all patients, the data collection officer was requested to record the qualifying values for cardiac troponin T, cardiac troponin I, CK-MB mass, CK-MB%, and CK, with the corresponding value for the upper limit of normal in the individual hospital. In addition, if subsequent values were significantly different from the qualifying value, the data collection officer was requested to enter the subsequent values. For patients who underwent a qualitative evaluation of cardiac troponin levels, we only recorded whether the patient did or did not have elevated levels, without a specific value.
In order to examine the extent of the troponin assay in our cohort, we examined the proportionof patients who had at least one examination of cardiac troponin levels reported at any time point.
In order to evaluate the correlation between biomarker levels and the diagnosis of MI, we included all patients who had at least one recorded value of any biomarker. For patients who had more than one creatine kinase assay, we ranked the biomarkers in the following hierarchy of priority, reflecting the descending degree of specificity of the assays: CK-MB mass, CK-MB%, or CK. For each patient we took the creatine kinase biomarker with the highest ranking of priority and calculated the ratio of its highest measured value to the upper limit of normal in the individual hospital. Thus, each patient was assigned a value for the ratio of the highest measured value of the most specific assay reported to the upper limit of normal of the assay in the individual hospital.
We examined the proportion of patients with elevated troponin levels who received a diagnosis of unstable angina, as well as the proportion of patients with normal troponin levels who received a diagnosis of Q-wave or non-Q-wave AMI.
Using different cutoff limits for the ratio the highest measured value of the creatine kinase assay chosen to the upper limit of normal of the chosen assay, ranging from >X1 upper limit of normal to >X10 upper limit of normal, we examined the proportion of patients with elevated creatine kinase biomarker levels who received a diagnosis of unstable angina, as well as the proportion of patients with normal biomarker levels who received a diagnosis of AMI.
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3. Results |
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Of the 5369 patients with available troponin and creatine kinase levels, 2226 patients (41.5%) had elevated levels of both markers (for creatine kinase, any level above the upper limit of normal), and 1422 patients (26.5%) had normal levels of both markers. Elevated troponin levels (i.e., with normal creatine kinase levels) alone occurred in 971 patients (18.1%), and elevated creatine kinase levels alone occurred in 750 patients (14.0%).
Of the 6036 patients with available troponin values, elevated troponin levels were recorded in 648 of 2307 (28.1%) patients with a discharge diagnosis of unstable angina and in 2957 of 3729 (79.3%) patients with a discharge diagnosis of AMI (Table 1).
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We also examined the use of troponins and the adherence to the new definition of AMI based on the academic status of the participating hospitals. Of the 6820 patients enrolled in academic hospitals, 3996 (58.6%) reported the result of at least one troponin assay, as compared with 1721 of 3022 patients (57.0%) in non-academic hospitals (p=0.13 for academic vs. non-academic hospitals). Of the 642 patients enrolled in hospitals that were not categorized based on academic status, 49.7% reported the result of a troponin assay. In academic hospitals, 23.2% and 79.8% of the patients with a discharge diagnosis of unstable angina and AMI, respectively, had elevated troponin levels. In non-academic hospitals, 36.8% and 77.2% of the patients with a discharge diagnosis of unstable angina and AMI, respectively, had elevated troponin levels (p<0.001 for comparison of discharge diagnosis of unstable angina, and p=0.08 for comparison of discharge diagnosis of AMI).
In order to determine whether the use of troponins or the adherence to the new definition of AMI changed over time, we divided the survey cohort into two groups; patients enrolled up to 31 December 2000 and those enrolled thereafter. Of the 7341 patients enrolled up to 31 December 2000, 651 patients (8.9%) either did not undergo an evaluation of cardiac biomarkers or had no record of the biomarker value in the case report form. Of the remaining 6690 patients, 4234 (63.3%) had at least one troponin level recorded. Of the patients with available troponin values, 2529 (59.7%) had at least one elevated value recorded; 468 (28.7%) of 1632 unstable angina patients and 2061 (79.2%) of 2602 AMI patients. Likewise, of the 6198 patients with available creatine kinase levels, 604 (23.6%) of the 2556 unstable angina patients and 2750 (75.5%) of 3642 AMI patients had at least one value above the upper limit of normal. Of the 3143 patients enrolled after 31 December 2000, 295 (9.4%) either did not undergo an evaluation of cardiac biomarkers or had no record of the biomarker value in the case report form. Of the remaining 2848 patients, 1802 (63.3%) had at least one troponin level recorded. Of the patients with available troponin values, 1076 (59.7%) had at least one elevated value recorded; 180 (26.7%) of 675 unstable angina patients and 896 (79.5%) of 1127 AMI patients. Likewise, of the 2673 patients with availablecreatine kinase levels, 244 (22.8%) of the 1069 unstable angina patients and 1198 (74.7%) of 1604 AMI patients had at least one value above the upper limit of normal. Thus, there was no significant difference between the two time periods.
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4. Discussion |
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4.2. Main finding
The new definition of AMI1was published on 4 September 2000. Our survey2that also began on 4 September 2000 offers unique insight regarding the implementation of this new definition in clinical practice. The main findings of our current analysis from this survey are that the recommended measures generating the new criteria, namely the troponin assays, were either not available or not used in a large proportion of ACS patients. Indeed, only 63.3% of the patients in our cohort underwent an examination for troponin levels.
Moreover, our current analysis demonstrates that a substantial proportion of ACS patients with elevated levels of cardiac biomarkers were given a diagnosis of unstable angina, and patients with normal levels of biomarkers were given a diagnosis of AMI. When we used higher levels of biomarkers to define AMI, the proportion of ACS patients with values above the cutoff level given a diagnosis of AMI substantially declined. Thus, it seems that some physicians still have not adopted the concept that any amount of myocardial necrosis caused by ischaemia constitutes AMI, but rather they demand a substantial amount of myocardial necrosis caused by ischaemia to define AMI.
4.3. Clinical implications
The implementation of new guidelines heavily relies on the availability of the required means to apply the recommendations. The current guidelines that define AMI require the availability of cardiac troponin assays. Perhaps of even greater clinical significance, cardiac troponin levels have a crucial role in tailoring the management of non-ST segment elevation ACS patients, based on current guidelines.5However, for some countries and some hospitals cardiac troponin assays remain beyond reach due to cost issues. Indeed, given that our survey included a substantial proportion of academic hospitals with revascularization facilities,2the true use of cardiac troponin assays in less well-equipped hospitals may be even smaller. Our results indicate that to conform to current guidelines in this broad region of Europe and the Mediterranean basin, there is a genuine need to increase the application of troponin assays, and more so to provide the means for their application.
Physician education is another key component of guideline implementation. Our results indicate that a substantial proportion of physicians who attend to ACS patients are either unaware of or have not accepted the new definition of AMI.6Alternatively, they may also not rely on the accuracy of the biochemical assays performed in their hospitals.68More efforts are therefore needed to disseminate the conceptual reasoning behind the new guidelines to ensure their more widespread acceptance and to increase the technical quality of biomarker assays. Indeed, if the technical shortcomings of current assays will not be resolved, the validity of the current definition may be challenged.7,8
4.4. Limitations
The limitations of the Euro Heart Survey ACS have been previously discussed in detail.2The final diagnosis given by the attending physician may have been erroneous. We did not examine the accuracy of the diagnosis, but rather its correlation to the recorded biomarker levels. In addition, we did not record the exact timing of the test reported, precluding any analysis regarding the interaction between procedures and adverse events and the rise in cardiac biomarkers. Because the serum levels of each biomarker have unique kinetics, the recorded values may reflect tests taken either too early or too late. To partially address this concern, in the current analysis we considered an abnormally high level of a biomarker at any time point to be suitable for a diagnosis of AMI. However, given the large proportion of patients that did not undergo cardiac troponin testing in our survey and that some of the troponin tests may have been performed either too early or too late, our finding of widespread discordance between biomarker levels and the final diagnosis probably underestimates the true extent of the phenomenon.
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5. Conclusions |
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Acknowledgments |
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References |
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