Cardiac troponins and anthracycline cardiotoxicity: a sub study of the PROACT trial; are all assays made equal?

The 2022 ESC Guideline[1] recommends cardiac troponin (cTn) monitoring during anthracycline chemotherapy to guide cardio-protection. However, it is unclear how consistently these recommendations can be implemented in routine practice when hospitals use a range of cTn assays.

To evaluate 4 highly sensitive cTn assays commonly used in clinical practice, focusing on the ability to detect mild anthracycline-induced Cancer Therapy Related Cardiac Dysfunction (CTRCD).

The PROACT trial[2] recruited 111 patients with breast cancer or non-Hodgkins’s lymphoma undergoing 6 cycles of anthracycline chemotherapy (planned ≥300mg/m² dox-equivalent). Blood samples were collected <72 hours before each cycle and 4 weeks post-therapy. Samples were centrally analysed at 4 NHS biochemistry departments using: Elecsys Troponin T Highly Sensitive Assay; Roche Diagnostics (cTnT), ARCHITECT STAT High Sensitivity Troponin I Assay; Abbott Laboratories (cTnI(A)), ADVIA Centaur High Sensitivity Troponin I Assay; Siemens Healthineers (cTnI(S)) and ACCESS High Sensitivity Troponin I Assay; Beckman Coulter (cTnI(BC)). The frequency of positive results (>ULN) by cycle was compared across assays. Units of change were compared by standardising peak cTn to the assay ULN, and averaging to baseline values. The potential impact on clinical decision making was assessed by comparing rates of mild CTRCD defined by each assay.

Marked differences were observed between assays. Notably, cTnT and cTnI(S) showed a 43% absolute difference in the proportion of patients exhibiting myocardial injury(Tab. 1). Differences were also evident between cTnI assays, with cTnI(BC) results aligning more closely with cTnT, while cTnI(A) and cTnI(S) had a lower sensitivity in detecting myocardial injury(Fig 1).

Consequently, diagnosis of mild CTRCD varied by assay. Using ECHO alone 18 (20%) patients were diagnosed (of 87 patients with complete GLS data). Combining ECHO with cTn the rates of CTRCD were: cTnT 76 (87%), cTnI(BC) 65 (75%), cTnI(A) 51 (59%) and cTnI(S) 43 (49%) patients. A limitation in comparing cumulative proportion of CTRCD was sample completeness, which was slightly lower for cTnI(S) (82%) and cTnI(BC) (83%) compared to original trial endpoints cTnT (92%) and cTnI(A) (88%).

When standardised to ULN, cTnT and cTnI(BC) showed the greatest proportionate rises from baseline(Tab. 1). When standardised to baseline results, cTnI(A) and cTnI(S) had the greatest proportional rise, although this did not translate into more samples >ULN.

The diagnosis of mild CTRCD varied significantly among commonly available cTn assays, reflecting differing sensitivities in detecting myocardial injury. These discrepancies highlight limitations in the current recommendation for guiding treatment decisions based on cTn >ULN in clinical practice. More research is required to understand the utility of different hs-Tn platforms and to standardise practice.Figure 1:

Frequency of Positive Results