Early Diagnosis of Myocardial Infarction with Sensitive Cardiac Troponin Assays Tobias Reichlin, M.D., Willibald Hochholzer, M.D., Stefano Bassetti, M.D.,Stephan Steuer, M.D., Claudia Stelzig, M.Sc., N Engl J Med 2009;361:858-67 R2. hoehoon Chung / Prof. soo joong Kim

Background Acute myocardial infarction Major cause of death and disability 15 million patients per year in the US. and Europe present to the emergency department Rapid identification of AMI is critical for the initiation of effective evidence-based medical treatment and management Electrocardiography and cardiac troponins  Current diagnostic cornerstones

Standard cardiac troponin Structural proteins unique to the heart Sensitive and specific markers of myocardial damage Very helpful for identifying patients with ACS Superior to all other clinically available biomarkers (myoglobin, CK-MB, myeloperoxidase, and heart fatty acid–binding protein) : Limitation Delayed increase in circulating levels  Low sensitivity at the time of a patient’s presentation Requires prolonged monitoring over a period of 6 to 12 hours  Delay in confirming a diagnosis

Methods Study design and population Clinical assessment The Advantageous Predictors of Acute Coronary Syndromes Evaluation (APACE) Ongoing prospective, international, multicenter study designe 2006.04 ~ 2008.04 , 786 consecutive patients Presented to the emergency department with symptoms chest pain and angina pectoris, Onset or peak of symptoms had occurred within 12 hours Patients with terminal kidney failure requiring dialysis were excluded. Clinical assessment Clinical history taking, physical examination 12-lead ECG, continuous ECG monitoring, pulse oximetry Standard blood measurements, and chest radiography Cardiac troponin I or cardiac troponin T, CK-MB, and myoglobin

Adjudicated Final Diagnosis Two independent cardiologists reviewed all available medical records AMI was defined in accordance with current guidelines. evidence of myocardial necrosis + clinical signs of ischemia. Necrosis was diagnosed on the basis of the local cardiac troponin level Investigational Assays of Cardiac Troponins Five investigational cardiac troponin assays Abbott–Architect Troponin I Siemens Troponin I Ultra Roche High-Sensitive Troponin T Roche Troponin I Blood samples at the time of the patient’s presentation to the ED. Additional samples were obtained 1, 2, 3, and 6 hours after presentation CK-MB and myoglobin were measured

Results

Characteristics of the Patients Unstable angina 16% Cardiac causes 13% Noncadiac causes 46% Unknown 8% 17%

Diagnostic Accuracy of Cardiac Troponin Levels at Presentation Figure 1. Levels of Cardiac Troponins at Presentation, as Assessed by Four Sensitive Assays and a Standard Assay, According to the Final Diagnosis.

Sensitive assays Standard assays AUC Abbott–Architect Troponin I 0.96 Roche High-Sensitive Troponin T 0.96 Roche Troponin I 0.94 Siemens Troponin I Ultra 0.96 Standard assay 0.90 Figure 2. Diagnostic Performance of Cardiac Troponin Assays at Presentation.

Cardiac Troponin Levels at Presentation in Patients with Recent Onset of Chest Pain Sensitive assays Standard assays AUC Abbott–Architect Troponin I 0.93 Roche High-Sensitive Troponin T 0.92 Roche Troponin I 0.92 Siemens Troponin I Ultra 0.94 Standard assay 0.76

3 hr Sensitive assays Standard assays 0.94 0.93 0.92 0.85 0.71 0.76 Figure 3. Diagnostic Accuracy of Cardiac Troponin Assays at Presentation According to Time since Onset of Chest Pain.

Conclusion The diagnostic performance of sensitive cardiac troponin assays is excellent. These assays can substantially improve the early diagnosis of acute myocardial infarction, particularly in patients with a recent onset of chest pain.