ABC | Volume 112, Nº3, March 2019

Review Article Early Detection and Monitoring of Cancer Chemotherapy-Related Left Ventricular Dysfunction by Imaging Methods Mario Luiz Ribeir o, Antonio José Lagoeiro Jorge , Marcelo Souto Naci f, Wolney de Andrade Martin s Universidade Federal Fluminense, Niterói, RJ – Brazil Keywords Neoplasms/mortality; Antineoplastic Agents/adverse effects; Ventricular Dysfunction, Left/diagnostic imaging; Anthracyclines/adverse effects; Trastuzumab/radiation effects. Mailing Address: Antonio José Lagoeiro Jorge • Avenida Marquês do Paraná, 303. Postal Code 24033-900, Centro, Niterói, RJ – Brazil Email: lagoeiro@cardiol.br , lagoeiro@globo.com Manuscript received March 05, 2018, revised manuscript November 21, 2018, accepted December 05, 2018 DOI: 10.5935/abc.20190022 Introduction Cancer has been the second leading cause of death in Brazil since 2006, and it is predicted to surpass cardiovascular disease (CVD) as the leading cause of death between 2020 and 2025. 1 Cancer and CVD have risk factors in common, such as obesity, sedentarism, arterial hypertension, tobacco use, diabetes mellitus, advanced age, and dietary pattern. The co-prevalence of cancer and CVD is therefore elevated. The diagnosis and prevention of both diseases may be carried out in an integrated manner. 2 Oncological treatment with chemotherapy (CT) has led to an increase in survival, but it has also led to the risk of cardiotoxicity (CTX), the incidence of asymptomatic ventricular dysfunction or even cardiomyopathy. 3 Early diagnosis of CTX is important, given that the sooner this myocardial event is diagnosed, the higher the chances of recovering systolic function. 4 The objective of monitoring left ventricular (LV) function during cancer treatment is to detect cardiac dysfunction during the subclinical phase, rather than when a symptomatic patient already has reduced ejection fraction. The groups of chemotherapeutic medications that most frequently cause myocardial aggression are anthracyclines (ANT), widely used in the treatment of solid tumors and hematological malignancies, and monoclonal antibodies, the typical example of which is trastuzumab (TZU). 5,6 The CTX of ANT was initially described as dose-cumulative, irreversible, and caused by mitochondrial injury. In contrast, TZU-related CTX, which is not dose dependent, is irreversible and does not cause mitochondrial injury. In both aggressions, however, the possibility of reverse remodeling and recovery of ventricular function has been reported. Case series of patients undergoing treatment with ANT reported an incidence of 15% to 17% of some degree of decrease in LV ejection fraction (LVEF), calculated by Simpson’s method, and 2% to 3% of severe heart failure (HF). 7 More recent case series, however, have related lower incidences. There are different definitions used for the diagnosis of ventricular dysfunction related to cancer treatment, which are extrapolated from diverse clinical situations and which have little specific validation. Currently, one of the most used definitions is as a decrease in LVEF of more than 10% of the baseline value, to values below the cutoff of 53%, with or without symptoms, it being necessary to repeat the exam 2 or 3 weeks after the initial measurement. 8 According to Zamorano et al. 9 this lower limit for LVEF normality is 50%, also with a 10% reduction. Other definitions quantify a decrease in LVEF of more than 10% to LVEF below 55%, in asymptomatic patients, or a decrease of more than 5% to LVEF below 55% in symptomatic patients. 10 Initially, endomyocardial biopsy was the gold standard used for cardiotoxicity, but its invasive character and risk of complications led to its progressive replacement by imaging methods. Various techniques have been proposed as tools for diagnosis and prognosis of CTX associated with CT, with emphasis on serum biomarkers, conventional echocardiography, two-dimensional strain echocardiography, radionuclide ventriculography (RNV), and cardiac magnetic resonance imaging (CMRI). The objective of this review is to present clinicians with the main advantages and disadvantages of different imaging methods for diagnosing and monitoring chemotherapy-related left ventricular dysfunction, regarding critical analysis, accuracy, limitations, and clinical perspectives. Methods This review followed adaptations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology principles. The bibliographic search included the databases MEDLINE, SciELO, and LILACS. The descriptors used were cardiotoxicity ; left ventricular dysfunction ; antineoplastics ; anthracyclines ; diagnostic techniques and procedures ; echocardiography ; Doppler echocardiography ; two-dimensional/three-dimensional/ contrast echocardiography ; scintigraphy ; nuclear medicine ; computed tomography ; magnetic resonance . The reference lists of the articles found in the electronic search were also consulted and relevant articles were, thus, identified. The objective was to answer the question which is the most appropriate imaging method for the early detection of ventricular dysfunction in patients submitted to cancer CT within the context of clinical practice. Two independent researchers independently analyzed all abstracts. The review considered original articles with the following study designs: clinical trial, cohort, case-control, meta-analysis, and reviews that had expert consensus; considering articles published in the period between January 1998 and June 2017, whose full texts were available in English, Spanish, or Portuguese. The studies were selected in accordance with the following criteria: (a) the underlying disease was cancer, with a diagnosis confirmed by histopathology; (b) treatment included CT with ANT, TZU, or other known myocardial depressants; and 309