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BACKGROUND Most patients presenting to the emergency department (ED) with suspected acute coronary syndrome (ACS) undergo noninvasive cardiac testing with a low diagnostic yield. We determined whether a combination of high-sensitivity cardiac troponin I (hs-cTnI) and cardiovascular risk factors might improve selection of patients for cardiac testing. METHODS We included patients from the Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) I and II trials who presented to the ED with acute chest pain and were referred for cardiac testing. Based on serial hs-cTnI measurements and cardiovascular risk factors, we derived and validated the criterion for no need of cardiac testing. We predicted the effect of this criterion on the effectiveness of patient management. RESULTS A combination of baseline hs-cTnI (&amp;lt;4 ng/L) and cardiovascular risk factors (&amp;lt;2) ruled out ACS with a negative predictive value of 100% in ROMICAT I. We validated this criterion in ROMICAT II, identifying 29% patients as not needing cardiac testing. An additional 5% of patients were identified by adding no change or a decrease between baseline and 2 h hs-cTnI as a criterion. Assuming those patients would be discharged from the ED without cardiac testing, implementation of hs-cTnI would increase ED discharge rate (24.3% to 50.2%, P &amp;lt; 0.001) and decrease the length of hospital stay (21.4 to 8.2 h, P &amp;lt; 0.001), radiation dose (10.2 to 7.7 mSv, P &amp;lt; 0.001), and costs of care (4066 to 3342 US$, P &amp;lt; 0.001). CONCLUSIONS We derived and validated a criterion for combined hs-cTnI and cardiovascular risk factors that identified acute chest pain patients with no need for cardiac testing and could improve effectiveness of patient management. ClinicalTrials.gov Identifiers: NCT00990262 and NCT01084239

High-Sensitivity Cardiac Troponin I as a Gatekeeper for Coronary Computed Tomography Angiography and Stress Testing in Patients with Acute Chest Pain