Long forms of cardiac troponin T in non-cardiac diseases with frequent troponin T elevations

Background

Elevations of cardiac troponin (cTn), particularly cardiac troponin T (cTnT), are common in non-cardiac diseases and may complicate clinical decision making and potentially lead to unnecessary invasive procedures. The currently used commercial high-sensitivity cTnT (hs-cTnT) assay detects all circulating cTnT molecules, including intact and fragmented forms (total cTnT). A novel uncommercialized cTnT assay measures only intact and mildly fragmented forms of cTnT (”long cTnT”). With this assay, preliminary studies have demonstrated improved discrimination between non-cardiac related cTnT elevations and myocardial infarction (MI), suggesting that long forms of cTn are more prevalent in MI.

Purpose

To study the molecular composition of cTnT across five non-cardiac disease groups frequently associated with hs-cTnT elevation and to determine whether long or fragmented cTnT forms predominate.

Methods

In this single-center prospective study we enrolled hospitalized patients during a period of 1.5 years across five non-cardiac disease groups: Chronic kidney disease stage 5 (CKD5), rhabdomyolysis (rhabdo), sepsis, stroke, and major orthopedic surgery. Patients with cardiac disease(s) were excluded. Patients underwent ECG, echocardiography, and cTnT measurements. Total cTnT was measured using a commercial hs-cTnT assay, and long cTnT with an investigational long cTnT immunoassay. Control groups of 30 patients with MI and 314 healthy individuals were included. The long-to-total cTnT ratio was calculated. Results are presented as median [IQR].

Results

Among 250 enrolled patients, 24 (9.6%) were excluded due to underlying cardiac disease. Of the remaining 226 patients with non-cardiac diseases (50.4% male, group sizes in Table 1), total cTnT exceeded the 99th percentile in 166 cases (73.5%). Total cTnT concentrations were highest in patients with CKD5 (60.9 [39.7–120.5] ng/L) and rhabdomyolysis (52.0 [24.9–139.2] ng/L), substantially overlapping with MI levels (103.0 [52.2–257.5] ng/L) and with no significant differences versus MI (both p = 0.06) (Figure 1; Table 1).

In contrast, long cTnT concentrations were consistently low in all non-cardiac patients (1.6 [1.1–2.8] ng/L) compared to MI patients (28.4 [7.2–114.3] ng/L; p<0.0001). The long-to-total cTnT ratio was markedly lower in non-cardiac diseases (0.06 [0.04–0.10]) than in MI (0.21 [0.13–0.49]; p<0.0001). CKD5 showed the lowest ratio (0.03 [0.02–0.05]), and surgery the highest (0.09 [0.06–0.14]) (all adjusted p<0.0001 vs. MI).

Conclusion

In non-cardiac diseases, total cTnT concentrations overlapped with MI, whereas both long cTnT concentrations and long-to-total ratios clearly distinguished ischemic from non-ischemic injury. These findings suggest that evaluating circulating cTnT composition, rather than total cTnT alone, may improve diagnostic discrimination and potentially reduce unnecessary invasive evaluation in patients with non-cardiac cTnT elevations.