A-011 Investigation Into The Prevalence and Clinical Impact Of Macrotroponin In An Emergency Department Patient Population

Background Macrotroponin is a complex formed between endogenous cardiac troponin autoantibodies and circulating cardiac troponin I (cTnI) that can cause elevated cTnI due to decreased renal clearance and analytical cross-reactivity. With the widespread adoption of high-sensitivity troponin assays (hs-cTnI), there is considerable interest in describing not only the prevalence, but also clinical impact, of macrotroponin on assayed hs-cTnI values, and ultimately the effect on patient clinical outcomes. Recent studies into macrotroponin prevalence have yielded a wide range of often conflicting values, ranging from a prevalence of 5% to 50%. The goal of this study is to determine the prevalence of macrotroponin in an emergency department population and establish correlations with clinical history of ischemic heart disease and inflammatory disorders. Methods Lithium heparin plasma from 88 emergency department patients with hs-cTnI greater than 40 ng/L were obtained. Plasma and a 25% w/v polyethylene glycol 6K in saline solution were combined at a 1:1 ratio. The mixture was incubated for 10 minutes, allowing for macrotroponin complexes to precipitate out of solution. The precipitated proteins were pelleted by centrifugation at 14,000g, and the resulting supernatant was assayed for hs-cTnI on the Abbott Alinity-i analyzer. A control trial was performed by assaying each patient plasma sample combined with a 1:1 ratio of plasma to saline. Macrotroponin-depleted hs-cTnI values were compared to control values to determine the % recovery of hs-cTnI for each patient. A chart review was performed to assess for: history of ischemic heart disease (CAD, STEMI, NSTEMI) and inflammatory disorders (RA, Lupus, etc.). An additional study was completed as described above to serve as a control population using 27 normal outpatient patient samples. Results % hs-cTnI recoveries were graphed as a frequency distribution, and we were able to observe a bimodal distribution of hs-cTnI % recoveries. Through this distribution, we were able to determine a % hs-cTnI recovery threshold of <20% as being macrotroponin (+). This afforded a prevalence of 18.1% in the ED patient population (16/88). Macrotroponin prevalence in the control population was 3.7% (1/27). No correlation was observed between patient sex, age and macrotroponin positivity. Further classifying emergency department population afforded higher rates of inflammatory disorders in macrotroponin (+) patients compared to macrotroponin (-) patients, 18.7% (3/16) vs. 8.3% (6/72). Rates of ischemic heart disease were identical in macrotroponin (+) and (-) patients, 50% (8/16, 36/72). Of macrotroponin (+) patients, no indication of inappropriate cardiac intervention was observed due to macrotroponin elevated hs-cTnI levels. Conclusions: Through our observed bimodal frequency distribution of hs-cTnI % recoveries we were able to confidently establish a % cut-off of <20% as being macrotroponin (+). This led to a macrotroponin prevalence of 18.1% in an ED patient population. Macrotroponin prevalence in non-ED populations is very low at 3.7%. Macrotroponin (+) patients had higher rates of inflammatory disorders, where higher levels of circulating autoantibodies could potentially aid in the formation of macrotroponin complexes. Despite the high prevalence of macrotroponin in ED patient populations, we observed no significant clinical impact due to macrotroponin elevated troponin levels.