Endothelial function trajectories during anthracycline chemotherapy by baseline cardiovascular risk: a prospective three-time point study
A Amanova, Z H Tlegenova, S Balmagambetova, G Kurmanalina, I Talipova, G Sultanbekova, K Kubenova, M Baspayeva, S Madinova, Z Bulekova, B ZholdinAbstract
Background
In patients receiving anthracycline therapy, a decline in FMD reflects the development of endothelial dysfunction and may represent an early vascular response preceding myocardial involvement. Nevertheless, whether early FMD changes can reliably predict subsequent asymptomatic left ventricular dysfunction remains an open question.
Purpose
To evaluate longitudinal changes in FMD according to baseline cardiovascular risk and to explore whether early FMD changes are associated with subsequent asymptomatic cancer-therapy-related cardiac dysfunction (CTRCD) during anthracycline therapy.
Methods
This prospective analysis included 71 women (mean age 55.4±11.2 years) receiving anthracycline-containing chemotherapy. Patients were stratified into a low-risk group (n=40) and a moderate-to-high-very high risk group (n=31)according to the HFA-ICOS risk assessment. Cardiovascular evolution, monitoring and definition of asymptomatic CTRCD followed the 2022 ESC cardio-oncology recommendations. FMD was measured at baseline (T0), after 4 cycles (T1), and after 8 cycles (T2) using a validated automated FMD analysis. Between-group difference and longitudinal changes in FMD were performed using appropriate non-parametric methods. The association between early FMD change and CTRCD was assessed using logistic regression with adjustment for baseline cardiovascular risk; an additional threshold analysis evaluated the upper quartile of early FMD decrease (≥0.70).
Results
Cumulative anthracycline dose was 225.0±44.5 mg/m² in the low-risk group and 209.1±45.1 mg/m² in the moderate-to-high-very high risk group. FMD values were consistently higher in the low-risk group than in the moderate-to-high-very high risk group at baseline (11.40% vs 7.80%; p<0.001), after 4 cycles (10.85% vs 7.10%; p<0.001), and after 8 cycles (10.60% vs 6.50%; p<0.001) (Figure 1). A significant decline in FMD over time was observed in both risk groups (p < 0.001). Asymptomatic LV dysfunction after 8 cycles occurred in 19/71 patients (26.7%), with no significant difference between risk groups. Early FMD decline was not associated with the occurrence of asymptomatic CTRCD in univariable analysis OR 1.06(95% CI 0.85-1.32) or after adjustment for baseline cardiovascular risk OR 1.09(95% CI 0.86-1.37). The threshold analysis (Early FMD decrease ≥0.70) also showed no difference in outcome frequency (p=0.699).
Conclusions
During anthracycline chemotherapy, FMD trajectories differ according to baseline cardiovascular risk, with consistently lower FMD values in patients with moderate-to-high risk. In this cohort, early decline in FMD was not associated with subsequent asymptomatic LV dysfunction, suggesting that endothelial dysfunction, while an early vascular response to chemotherapy, may not be sufficient as a stand-alone predictor of CTRCD.Figure 1