Elevations in Troponin T and I Are Associated With Abnormal Tissue Level Perfusion: A TACTICS-TIMI 18 Substudy

Background—Cardiac troponin T (cTnT) and I elevations are associated with a higher risk of adverse events, a higher incidence of multivessel disease, complex lesions, and visible thrombus in the setting of non-ST elevation (NSTE) acute coronary syndromes (ACS). Other pathophysiological mechanisms underlying troponin elevation remain unclear. Methods and Results—We evaluated the relationship between troponin elevation and tissue level perfusion using the TIMI myocardial perfusion grade (TMPG) in 310 patients with NSTE-ACS in the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction (TACTICS-TIMI) 18 trial. TMPG 0/1 (“closed” microvasculature) was observed more frequently in cTnT-positive patients both before (58.1% versus 42.1%;P =0.007) and after percutaneous coronary intervention (55.4% versus 35.6%;P =0.004). cTnT levels were higher among patients with TMPG 0/1 versus patients with TMPG 2/3 (0.50 versus 0.31 ng/mL;P =0.006). cTnT-positive patients were more likely to have thrombus (42.5% versus 29.3%), tighter stenoses (72.0% versus 64.8%), and higher rates of TIMI flow grade 0/1 (15.6% versus 7.0%; all P <0.05). TMPG 0/1 remained independently associated with cTnT elevation (odds ratio, 1.81;P =0.02), even after adjusting for epicardial TIMI flow grade, presence of thrombus, and prior myocardial infarction. TMPG 0/1 flow both before and after intervention was associated with increased risk of death or myocardial infarction at 6 months. Conclusions—Similar to what has been observed in the setting of ST-elevation myocardial infarction, abnormal tissue level perfusion is also associated with adverse outcomes in the NSTE-ACS setting. Independent of the presence of thrombus and abnormal flow in the epicardial artery, impaired tissue level perfusion is associated with a 1.8-fold increased risk of cTnT elevation.