Circulation. 2020 Dec 10. doi: 10.1161/CIRCULATIONAHA.120.046574. Online ahead of print.
Background: Cardiac troponins (cTns) are the cornerstone of diagnosing acute myocardial infarction (MI). There is limited knowledge on the duration of ischemia necessary to induce a measurable release of cTns or the very early release kinetics of cTns following an ischemic event. Copeptin may have a supplementary role in ruling out MI early. We investigated the release of cTns and copeptin in the first hours after experimental balloon-induced ischemia in humans. Methods: Thirty-four patients (median age, 60 years [IQR 51-64]; 15 males, 43%) with angiographically normal coronary arteries were randomized into four groups with different durations of induced myocardial ischemia (0, 30, 60, 90 seconds). Ischemia was induced by inflating a balloon in the left anterior descending artery (LAD) between the first and second diagonal branch. Blood was collected prior to balloon inflation (baseline) every 15 min for the first 3 h, and every 30 min for the next 3 h. The cTns were analyzed by three high-sensitivity assays: hs-cTnT (Roche), hs cTnI (Siemens), and hs-cTnI (Abbott). Copeptin was analyzed by a sandwich immunoluminometric assay. Results: None of the patients had any complications. Increased cTn concentrations were detected by all three assays, and the magnitude of the increase was associated with the duration of ischemia. Increased hs-cTnI (Siemens) concentrations were first detectable 15 min after 90 s ischemia (median 43.7% increase) and increased more steeply and had a higher peak than the other assays. Copeptin levels did not significantly change. Using the cTnT, hs-cTnI (Siemens), and hs-cTnI (Abbott) concentrations at 0 min and 180 min, 1 (11%), 0, and 0 patients from the 60 s ischemia group and 5 (63%), 2 (25%), and 1 (11%) from the 90 s ischemia group, respectively, fulfilled criteria for a biochemical MI. Conclusions: This study is the first to report the early release kinetics of cTn concentrations following different durations of experimental coronary balloon occlusion in humans. All assays detected a cTn increase after only 30 seconds of ischemia. Hs-cTnI (Siemens) rose faster and reached a higher peak. Copeptin levels did not significantly change. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03203057.