Usefulness of ultra-sensitive troponin to predict anthracyclines and trastuzumab related cardiac dysfunction

Abstract

Abstract Background Cancer therapeutics–related cardiac dysfunction usually known as cardiotoxicity (CTX) is a common adverse effect of anthracyclines and anti-Her2 agents. In recent years, evidence of usefulness of ultrasensitive troponin for early diagnosis of CTX has increased, however the cut-off values of this biomarker remain uncertain. Purpose To assess the usefulness of ultrasensitive troponin T (UsTnT) to identify patients at risk of developing CTX and determine cut-off values for this biomarker. Methods Patients with diagnosis of solid or hematologic malignancies scheduled to receive therapy including anthracyclines and/or trastuzumab were prospectively included. Echocardiogram was performed prior to chemotherapy, and repeated 3 and 6 months later. UsTnT was measured at baseline and 3 months after starting chemotherapy and the increase of this biomarker from baseline was calculated. This UsTnT has a range of 3–10,000 pg/mL with a 99th percentile <15 pg/mL. Receiver operating characteristic curve was used to find out the best cut-off values followed by a multivariate analysis. The primary endpoint was the presence of CTX defined as a decline of left ventricular ejection fraction (LVEF) ≥10% at 6 months from baseline. Results A total of 141 patients were included (mean age 56±15 years, 85,8% were women, the most frequent diagnosis being breast cancer: 61.7%). Thirty-three patients (23.4%) met criteria of the primary endpoint of CTX. Patients with CTX showed significantly higher values of UsTnT at 3 months (18.2±14,9 vs 11.8±10,7 pg/mL, p=0.008) and also showed a higher increase of UsTnT from baseline (11.8±12.8 vs 5±8.2 pg/ml, p<0.001) (figure 1). The value of UsTnT at 3 months ≥13 pg/mL and an increase of UsTnT from baseline ≥14 pg/mL were selected as the best cut-off values. Figure 2 resumes sensitivity, specificity and predictive values. Those patients who had UsTnT at 3 months ≥13 pg/mL had a 3.8 fold increased risk of developing CTX in a multivariate analysis adjusted by age and left ventricular hypertrophy (OR: 3.8 [95% CI: 1.6–9.3], p=0.003) while an increase of UsTnT from baseline ≥14 pg/mL showed almost 12 fold increased risk for the primary endpoint in the same model (OR: 11.95 [95% CI: 3.9–36.6], p<0.001). Conclusions UsTnT is a good biomarker for detecting early myocardial injury which allows the identification of patients at risk for developing CTX with only two measurements during cancer treatment. Funding Acknowledgement Type of funding sources: None.