Led by Christian Mueller of the University Hospital Basel, Switzerland, in collaboration with the University Hospitals of Zurich (Limmattalspital) and Olten (Kantonsspital) in his home country, as well as the hospitals of Herz Zentrum Bad Krozingen, Germany, and del Mar, Barcelona, Spain, four ultrasensitive troponins (hs-cTn) were evaluated for their early diagnostic value in patients with acute heart attack (AMI) in the emergency room. Mar) Hospital, Germany and Herz Zentrum Bad Krozingen and Hospital del Mar, Barcelona, Spain, evaluated the value of four ultrasensitive troponins (hs-cTn) for the early diagnosis of patients with acute heart infarction (AMI) in the emergency room. A total of 786 patients were included in the study, of which 68 were excluded due to lack of troponin (cTn) values. Seventeen percent (123/718) of those enrolled were diagnosed with myocardial infarction, 16% with unstable angina, 13% with cardiac syndromes that excluded coronary artery disease, 46% with non-cardiac syndromes, and 8% with unclear etiology. Patients with end-stage renal failure requiring dialysis were excluded. Patients with suspected AMI in the emergency department had presented with symptoms within 12 hours before presentation. Two cardiologists made the diagnosis based on clinical history, laboratory, coronary, imaging, and electrocardiographic findings. If the diagnoses differed, a third expert further discriminated. AMI was diagnosed using the current guidelines: ischemic symptoms with myocardial necrosis. Myocardial necrosis was diagnosed by at least one cTn measurement greater than or equal to the 10% lowest tertile or an upward/downward change. Unstable angina was diagnosed by normal troponin levels at rest but with typical angina, or worsening stable angina and a positive cardiac exercise test, or coronary artery stenosis greater than 70% by cardiac catheterization, or an ill-defined diagnosis of AMI, or an infarction or sudden cardiac death within 60 days of presentation. Patients had blood samples taken at the time of presentation, and 1, 2, 3, and 6 hours after presentation. Serum samples were assayed by four ultrasensitive troponin (hs-cTn) assays (Abbott Architect cTnI, Siemens cTnI Ultra, Roche hs-cTnT, and Roche cTnI) and one conventional cTn (Roche fourth generation cTnT) assay. The sensitivity and specificity of the different detection systems for the diagnosis of AMI were determined by observing the positive and negative rates of the first cTn after consultation in the case group and the unstable angina group, respectively, using the cut-off shift method. Statistical software was used to calculate the positive and negative predictive values at different diagnostic thresholds and depict the ROC curves. The diagnostic efficacy of AMI was expressed as the area under the ROC curve (AUC). RESULTS: Abbott, Siemens, Roche hs-cTnT, Roche cTnI, and Roche fourth-generation cTnT AUCs and their 95% confidence intervals (CIs) were 0.96 (0.94-0.98), 0.96 (0.94-0.98), 0.96 (0.94-0.98), 0.94 (0.92-0.97), 0.90 (0.86- 0.94). The AUC of the four hs-cTn was significantly higher than that of the conventional cTn, with p-values of 0.01, 0.008, 0.06, and 0.009, respectively. there was no significant difference in diagnostic accuracy among the four hs-cTn. hs-cTn had similar diagnostic accuracy for non-ST-segment elevation and ST-segment elevation AMI. The superiority of hs-cTn was better demonstrated for the diagnosis of patients within 3 hours of the onset of chest pain, with AUCs of 0.93 (0.88-0.99), 0.94 (0.90-0.98), 0.92 (0.87-0.97), 0.92 (0.86-0.99), and 0.76 (0.64-0.88), respectively. The results of the experiment showed that combined CK-MB mass and myoglobin measurements and significantly increased diagnostic efficacy over cTn results alone. The cTn levels in patients with unstable angina were significantly lower than those in patients with AMI, and were similar to those in patients with other cardiac causes of chest pain, but significantly higher than those with non-cardiac causes of chest pain. Four main conclusions were drawn from this study: ① The diagnostic efficacy of the four hs-cTn was high at the time of patient consultation, with an AUC of 0.94-0.96; ② The diagnostic efficacy of the hs-cTn assay was higher than that of the traditional cTn assay as demonstrated by the multicenter experiment; ③ The superiority of the hs-cTn is mainly reflected in the fact that it is capable of early diagnosis of AMI in the short time of the onset of chest pain compared with the traditional method, providing AMI patients with the opportunity of early treatment and reducing the complications. It provides an opportunity for early treatment of patients with AMI and reduces complications; (4) the diagnosis of AMI can be reliably ruled out based on the initial hs-cTn measurement, as the negative predictive value of various methods is 97-99% at the 99th percentile of the threshold value. hs-cTn, when combined with the results of clinical evaluations, such as electrocardiograms, can greatly reduce the chances of patients with diagnostic uncertainty to undergo follow-up examinations. The authors also point out that despite the superior diagnostic performance of ultrasensitive troponin assays, they should be combined with clinical evaluation; for example, a comprehensive clinical evaluation is needed to differentiate between AMI and elevated troponin levels caused by other conditions, including myocarditis and heart failure. Early diagnosis and treatment of acute myocardial infarction (AMI) is beneficial in improving the prognosis of patients with chest pain. Traditional markers of myocardial necrosis have high diagnostic value but poor sensitivity within 1 hour of chest pain. The recent emergence of an ultrasensitive troponin (hs-cTn) assay with a 10% CV below the 99th percentile may remedy this deficiency. This hs-cTn assay can increase the accuracy of AMI diagnosis and improve diagnostic sensitivity and specificity. However, there is a lack of large-scale multicenter prospective studies on the role of hs-cTn assay in the early diagnosis of AMI. Professor Till Keller of the University Medical Center Mainz, Germany, led a joint study with 3 German, 2 American, and 1 French hospitals to evaluate the accuracy and clinical significance of hs-cTnI measurement in the early diagnosis of MI. The study enrolled 1,818 patients with chest pain who underwent hs-cTnI, conventional cTnT, and total CK, CK-MB mass, and myoglobin measurements at a series of time points after hospital admission. The hs-cTnI was measured using a Siemens cTnI (Ultra) and the conventional cTnT was measured using a Roche fourth-generation cTnT. The final diagnosis of AMI was arrived at by two cardiologists combining clinical, laboratory and imaging findings. The diagnostic criteria for conventional cTn are: measurements exceeding 10% imprecision at the point of detection and a change of more than 20% over a 6-hour period. hs-cTnI diagnostic criteria are: measurements exceeding the 99th percentile (0.04 ng/ml) in a healthy population and a change of more than 30% over a 6-hour period. hs-cTnI 99th percentile values are from the Gutenberg Heart Study. Gutenberg Heart Study, which included 5000 subjects. AMI was finally diagnosed in 413 (22.7%) of 1818 patients, with non-ST-segment elevation MI accounting for 7%. hs-cTnI had the highest diagnostic performance and was even more sensitive than myoglobin. The area under the ROC curve (AUC) was 0.95 within 3 hours of chest pain, and increased slightly to 0.96 between 6 and 12 hours after chest pain. hs-cTnI had a clinical sensitivity of 90.7% and a specificity of 90.2%. When hs-cTnI exceeded the 99th percentile and changed by more than 30% within 6 hours of admission as a diagnostic criterion, the negative predictive value for patients within 3 hours of chest pain was 84.1% and the positive predictive value was 86.7%. MI was detected in 88% of patients with chest pain within 6 hours and in 95% of patients with chest pain between 6 and 12 hours. hsTnI elevation (greater than the 99% quartile value of 0.04 ng/ml) was independently associated with an increased risk of 30-day adverse regression (hazard ratio 1.96, 95% confidence interval 1.27-3.05; P=0.003). The results of the study showed that: (i) hs-cTnI has high sensitivity for diagnosing AMI; (ii) a 20% change in cTn measurements has traditionally been used as a criterion for diagnosing MI because 20% is twice the maximum imprecision, and if the change is greater than that, it is considered to be small due to analytic variability. Simultaneous observation of hs-cTn changes and using a change in hs-cTn of greater than 30% as a diagnostic criterion would also have the desired sensitivity and improve diagnostic specificity in patients with chest pain. The authors noted that in ischemia without clinical manifestations, elevated cTn can prompt physicians to look for other causes of myocardial necrosis (e.g., myocarditis, pulmonary embolism, congestive heart failure, renal failure, etc.). In addition, whether early diagnosis of MI facilitates the early application of interventional therapy to improve patient prognosis needs to be further investigated. Numerous preclinical and clinical trials have consistently concluded that troponin is more sensitive and specific for myocardial injury than CK-MB, and since 1999 troponin has been used as the marker of choice for assessing the diagnosis of AMI, replacing the CK-MB test in some countries. When troponin was first used in the clinic, the manufacturer recommended that its threshold value be derived from a comparison with the results of the CK-MB test, which clearly reduced its diagnostic sensitivity. Since 2000, guidelines have recommended the use of the 99th percentile of healthy individuals as a single threshold for the diagnosis of AMI, with a CV of less than 10% at this diagnostic threshold. Reagents that meet this performance are called ultrasensitive cTn (hs-cTn). Until 2009, most of the manufacturers Roche, Beckman, J&J, Abbott, Siemens have launched hs-cTn test reagents. The results of large-scale, multi-center, controlled studies in the international arena show that hs-cTn and its dynamic changes (>30%) can improve the positivity and specificity of AMI when combined with clinical and laboratory tests. Of course, the high sensitivity of hs-cTn is accompanied by an increase in the positivity rate in patients with cardiac syndromes with non-coronary artery disease, which requires clinicians to carefully analyze the trade-offs, consider the reasons for the increase in cTn, and do further testing. hs-cTn can be used for the earlier diagnosis of AMI, which should be of great concern to the testing community and cardiovascular specialists in China. It is believed that with the popularization of ultrasensitive troponin assay and the emergence of more clinical trials, the guidelines for the application of cardiac markers based on evidence-based medicine should be revised in time. This will potentially change the prognosis for the treatment of myocardial infarction.