Estimating the true half-life of cardiac troponins, a novel methodological approach

Abstract Introduction Cardiac troponins (cTn) are key when diagnosing myocardial injury (MI) and are used worldwide. Still, the half-life (T½) of cTn in the bloodstream is largely unknown. Previously, T½ has been estimated to 7-20 hours following MI. However, in the clinical setting the true T½, i.e. the decay of cTn, cannot be estimated due to ongoing leakage of cTn from cardiomyocytes. Identification of the true T½ is essential to improve estimation of how long cTn leak from cardiomyocytes due to MI and to understand the pathophysiology of all diseases in the myocardium associated with raised cTn levels. Purpose To determine T½ of cTnI and cTnT in the human blood stream. Methods Patients with ST elevation myocardial infarction (STEMI) were included within 24 hours after acute reperfusion therapy and underwent plasmapheresis to "harvest" plasma with a high cTn concentration. Three to 17 weeks later patients received a re-transfusion of autologous plasma. Blood samples were drawn at 22 fixed time points over eight hours from re-transfusion. A two phased model was used to estimate T½ of cTnI and cTnT for all patients. An alpha level of <0.05 was considered statistically significant and differences were tested by Wilcoxon matched pairs signed rank test. Results A total of 20 participants received a re-transfusion of their own plasma. Median age was 63 years (IQR 58-70), and four participants were women (20%). Prior to re-transfusion the participants’ median concentration of cTnI was 16 ng/l (interquartile range (IQR) 12-24) and of cTnT 12 ng/l (IQR 11-18). Following re-transfusion of 180-679 ml autologous plasma, participants’ concentration of cTn was measured again. Median concentration of cTnI was 3,355 ng/l (IQR 2,135-4,690) and of cTnT 237 ng/l (IQR 160-303 ng/l). Decay of cTnI and cTnT from injection to eight hours after followed a two-phased exponential decline with a primary fast and secondary slow phase as presented in figures 1-2. Each colored curve represents a participant. Median T½ during the first phase was 11 min for cTnI (IQR 6-13 min) and 15 min for cTnT (IQR 7-18 min). The fast decline in the first phase was thought to be due to re-distribution in the extracellular space. The second phase had a median T½ of 65 min for cTnI (IQR 56-80 min) and 67 min for cTnT (IQR 51-92 min). The second phase represents the human, biological T½ of cTn. No significant difference was found between T½ of cTnI and cTnT. Conclusions This novel study design showed seven to 20-fold shorter T½ of cTnI and cTnT compared to previous estimates in the acute, clinical setting, indicating that the duration of cTn leakage from the myocardium during MI has previously been grossly underestimated. This finding challenges our understanding and interpretation of the clinical course of MI and may translate into changes in the perceived window of opportunity for myocardial salvage by interventions.Figure 1:Cardiac troponin IFigure 2:Cardiac troponin T