Anthracycline Dose, Myocardial Injury, and Change in Left Ventricular Function in the Cardiac CARE Trial

Background Anthracycline-induced toxicity contributes to long-term cardiovascular morbidity in cancer survivors. Cardiac troponin is recommended for risk stratification and diagnosis, but the relationship between troponin concentrations—particularly those measured using high-sensitivity assays—and subsequent cardiac dysfunction remains unclear. Objectives The authors sought to examine associations between high-sensitivity cardiac troponin I (hs-cTnI), cumulative anthracycline dose, number of treatment cycles, and changes in left ventricular (LV) function. Methods The Cardiac CARE trial was a prospective, multicenter, randomized, open-label, blinded-endpoint study of cardioprotective therapy in patients with elevated baseline hs-cTnI undergoing high-dose anthracycline chemotherapy. Hs-cTnI was measured before each chemotherapy cycle and at 2, 4, and 6 months after treatment. LV function was assessed by cardiac magnetic resonance at baseline and 6 months post-chemotherapy. Results Of the 175 participants (mean age 52 ± 11 years; 86.5% women), 171 received ≥3 anthracycline cycles. The median cumulative epirubicin-equivalent dose was 600 mg/m ² (Q1-Q3: 513-660 mg/m ²). Peak hs-cTnI concentrations were observed 2 months after chemotherapy (median 14.0 ng/L [Q1-Q3: 9.0-30.5 ng/L]) and statistically correlated with the number of treatment cycles, but not with cumulative dose. No participants developed an LV ejection fraction (LVEF) <50%, although 24 of 171 patients (14.0%) experienced a decline in LVEF >10%. Hs-cTnI showed a weak correlation with LVEF change and was not predictive of global longitudinal strain by cardiac magnetic resonance. Conclusions Hs-cTnI levels were not associated with cumulative anthracycline dose and were only weakly associated with LVEF decline at 6 months. These findings suggest that mild myocardial injury, as reflected by hs-cTnI elevation, may not reliably predict subsequent cardiac dysfunction following anthracycline chemotherapy.