Baseline early diastolic mitral annular velocities and cancer therapy related cardiac dysfunction in HER2 therapy
A Chowdhury, C Soh, T Carrello, Af Chowdhury, J Stewart, R Nandurkar, O Musameh, J Chen, K K Premkumar, H Zheng, D Day, S Ramkumar, N Nerlekar, S TanAbstract
Introduction
Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) are used to diagnose cancer therapy-related cardiac dysfunction (CTRCD) in patients treated with HER2 targeted therapy. There is a paucity of data on whether tissue doppler parameters such as septal e’ and lateral e’ velocities are associated with CTRCD development.
Purpose
Determine the association between baseline septal and lateral e’ with subsequent CTRCD among patients who received HER2 therapy.
Methods
We conducted a single-center retrospective cohort study of 589 patients taking HER2-targeted therapy for cancer from 2006-2023. Patients underwent serial cardiac imaging at baseline and 3-monthly intervals. Baseline demographics and TTE parameters were recorded. CTRCD was defined as either symptomatic heart failure or new asymptomatic LVEF reduction by ≥10% to LVEF 40-49%. Logistic and Cox regression were performed to identify if septal e’ and lateral e’ were associated with subsequent CTRCD, adjusted for age, sex, hypertension and diabetes.
Results
A total of 589 patients (mean age 54.4 years, 99.2% female, 92.9% breast cancer) who received HER2-targeted therapy at baseline were included. Anthracycline treatment was also used in addition to HER2 therapy in 45.5% of patients. CTRCD occurred in 51 patients (8.7%). On logistic regression analysis, higher baseline septal e’ was associated with reduced risk of subsequent CTRCD (OR 0.57 for each 1.0cm/s increase, 95% CI 0.31-0.93, p=0.04), whilst there was no association for lateral e’ (OR 0.77 for each 1.0cm/s increase, 95% CI 0.52-1.09, p=0.16). Similar results were obtained on Cox regression analysis for septal e’ (HR 0.66, 95% CI 0.44-0.99, p=0.047) and lateral e’ (HR 0.81, 95% CI 0.61-1.11, p=0.16). On receiver operating characteristic analysis, septal e′ demonstrated good discriminatory performance (AUC 0.77), with an optimal threshold of 5.5cm/s yielding a sensitivity of 55.6% and specificity of 88.2%, whereas lateral e′ showed a slightly poorer discrimination (AUC 0.68), with a threshold of 9.1cm/s providing a sensitivity of 66.7% and specificity of 68.8%.
Conclusion
Baseline septal e’ was associated with subsequent CTRCD in cancer patients who received HER2 therapy. Further prospective studies are required to evaluate it is an effective risk stratification tool for CTRCD.