ABC | Volume 110, Nº2, February 2018

Original Article Global Longitudinal Strain Accuracy for Cardiotoxicity Prediction in a Cohort of Breast Cancer Patients During Anthracycline and/or Trastuzumab Treatment Eliza de Almeida Gripp, Gabriela Escudini de Oliveira, Luiz Augusto Feijó, Marcelo Iorio Garcia, Sergio Salles Xavier, Andréa Silvestre de Sousa Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ – Brazil Mailing Address: Eliza de Almeida Gripp • Rua Belisário Távora, 302 / 101 – 2. CEP 22245-070, Laranjeiras, Rio de Janeiro, RJ – Brazil E-mail: elizagripp@cardiol.br , elizagripp@yahoo.com.br Manuscript received July 13, 2017, revised manuscript February 10, 2017, accepted November 08, 2017 DOI: 10.5935/abc.20180021 Abstract Background: The high cardiotoxicity morbidity and mortality rates associated with the antineoplastic therapy for breast cancer could be reduced with the early use of cardioprotective drugs. However, the low sensitivity of left ventricular ejection fraction limits its use in that preventive strategy. New parameters, such as global longitudinal strain, are being used in the early detection of contractile function changes. Objectives: To assess the incidence of cardiotoxicity in patients treated for breast cancer, the independent factors associated with that event, and the ability of strain to identify it early. Methods: Prospective observational study of consecutive outpatients diagnosed with breast cancer, with no previous antineoplastic treatment and no ventricular dysfunction, who underwent anthracycline and/or trastuzumab therapy. The patients were quarterly evaluated on a 6- to 12-month follow-up by an observer blind to therapy. Cox regression was used to evaluate the association of cardiotoxicity with clinical, therapeutic and echocardiographic variables. A ROC curve was built to identify the strain cutoff point on the third month that could predict the ejection fraction reduction on the sixth month. For all tests, the statistical significance level adopted was p ≤ 0.05. Results: Of 49 women (mean age, 49.7 ± 12.2 years), cardiotoxicity was identified in 5 (10%) on the third (n = 2) and sixth (n = 3) months of follow-up. Strain was independently associated with the event (p = 0.004; HR = 2.77; 95%CI: 1.39-5.54), with a cutoff point for absolute value of -16.6 (AUC = 0.95; 95%CI: 0.87-1.0) or a cutoff point for percentage reduction of 14% (AUC = 0.97; 95%CI: 0.9-1.0). Conclusion: The 14% reduction in strain (absolute value of -16.6) allowed the early identification of patients who could develop anthracycline and/or trastuzumab-induced cardiotoxicity. (Arq Bras Cardiol. 2018; 110(2):140-150) Keywords: Breast Neoplasms/drug therapy; Cardiotoxicity; Stroke Volume; Trastuzumab; Indicators ofMorbidity andMortality Introduction Advances in the treatment of several tumors, such as the new antineoplastic drugs, have improved the survival of patients with cancer, resulting in more than 12 million survivors. 1 That, however, has allowed the identification of side effects, such as cardiotoxicity, responsible for an increase in mortality. 2,3 In 2016, the European Society of Cardiology has published a position paper recommending the diagnosis of cardiotoxicity be made in the presence of an ejection fraction (EF) reduction >10% for values below normality (53%). 4 Prior to that publication, different definitions of cardiotoxicity were used, hindering the assessment of its real incidence. 2 The most commonly used definition has been elaborated by the committee of cardiac review and assessment of trastuzumab-related cardiotoxicity, and consists of a reduction of 5% or more in EF values lower than 55%, accompanied by signs and/or symptoms of heart failure (HF), or a reduction of 10% or more in EF values lower than 55%, without clinical findings of HF. 5-8 Cardiotoxicity is a well-established side effect of several antineoplastic drugs, particularly anthracyclines and trastuzumab, used for breast cancer treatment. 9,10 The identification of patients at high risk for developing cardiotoxicity would be the ideal strategy to reduce mortality. Global longitudinal strain (GLS) is used in clinical practice aimed at the early detection of changes in myocardial contractile function. 11 However, neither GLS use nor its cutoff point to predict cardiotoxicity have been standardized. The American Society of Echocardiography and the European Association of Cardiovascular Imaging have agreed that deformity changes precede ventricular dysfunction. 140