Baseline Global Longitudinal Strain Predictive of Anthracycline-Induced Cardiotoxicity

Abstract

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.

Current Status and Trends of Research on Anthracycline-Induced Cardiotoxicity from 2002 to 2021: A Twenty-Year Bibliometric and Visualization Analysis

“…A reduction in GLS of >15% from baseline is generally considered an early sign of heart failure. Recent studies that applied GLS to guide clinical decision-making have reduced the incidence of cancer therapy-related cardiac dysfunction [64]. Accordingly, GLS might be a preferred index for early detection of cardiotoxicity during ANT therapy.…”

Novel molecular biomarkers of cancer therapy‐induced cardiotoxicity in adult population: a scoping review

“…7,8 The cardiac imaging societies define cardiotoxicity as a serial decline of left ventricular ejection fraction (LVEF) despite symptoms, 9 and despite existence of other cardiac imaging parameters, such as global longitudinal strain (GLS), which could be used to predict CTRCD. 10 In addition, the LVEF as a diagnostic tool for early cardiomyopathy has poor sensitivity and variable reproducibility, 11 highlighting the need to identify novel cardiotoxicity biomarkers. The molecular biomarkers (as protein, DNA, or RNA), among other characteristics, must detect cardiac lesions in earlier stages of the disease, monitoring the therapeutic benefit of cancer therapy with the risk of cardiotoxicity and identifying high-risk patients who required closer cardiac surveillance or the establishment of cardioprotective strategies.…”

“…The cardiotoxic events include myocardial dysfunction, heart failure (HF), coronary artery disease, valvular disease, arrhythmias, pericardial disease, hypertension, and thrombolytic events, among others 7,8 . The cardiac imaging societies define cardiotoxicity as a serial decline of left ventricular ejection fraction (LVEF) despite symptoms, 9 and despite existence of other cardiac imaging parameters, such as global longitudinal strain (GLS), which could be used to predict CTRCD 10 . In addition, the LVEF as a diagnostic tool for early cardiomyopathy has poor sensitivity and variable reproducibility, 11 highlighting the need to identify novel cardiotoxicity biomarkers.…”