Baseline Global Longitudinal Strain Predictive of Anthracycline-Induced Cardiotoxicity

Background: Anthracycline-induced cardiotoxicity is a major source of morbidity and mortality in long-term cancer survivors. Impaired GLS predicts decreased left ventricular ejection fraction (LVEF) in patients receiving anthracyclines, but knowledge regarding the clinical utility of baseline GLS in patients at low-risk of anthracycline-induced cardiotoxicity is limited. Objectives: The purpose of this study was to investigate whether baseline echocardiographic assessment of global longitudinal strain (GLS) before treatment with anthracyclines is predictive of cardiotoxicity in a broad cohort of patients with normal baseline LVEF..Methods: Study participants comprised 188 patients at a single institution who underwent baseline 2-dimensional (2D) speckle-tracking echocardiography before treatment with anthracyclines and at least one follow-up echocardiogram 3 months after chemotherapy initiation. Patients with a baseline LVEF <55% were excluded from the analysis. The primary endpoint, cardiotoxicity, was defined as an absolute decline in LVEF >10% from baseline and an overall reduced LVEF <50%. Potential and known risk factors were evaluated using univariable and multivariable Cox proportional hazards regression analysis. Results: Twenty-three patients (12.23%) developed cardiotoxicity. Among patients with cardiotoxicity, the mean GLS was -17.51% ± 2.77%. The optimal cutoff point for cardiotoxicity was -18.05%. The sensitivity was 0.70 and specificity was 0.70. The area under ROC curve was 0.70. After adjustment for cardiovascular and cancer therapy related risk factors, GLS or impaired baseline GLS ≥-18% was predictive of cardiotoxicity (adjusted hazards ratio 1.17, 95% confidence interval 1.00, 1.36; p=0.044 for GLS, or hazards ratio 3.54; 95% confidence interval 1.34, 9.35; p = 0.011 for impaired GLS), along with history of tobacco use, pre-chemotherapy systolic blood pressure, and cumulative anthracycline dose. Conclusions: Baseline GLS or impaired baseline GLS was predictive of cardiotoxicity before anthracycline treatment in a cohort of cancer patients with a normal baseline LVEF. This data supports the implementation of strain-protocol echocardiography in cardio-oncology practice for identifying and monitoring patients who are at elevated risk of anthracycline-induced cardiomyopathy.