Copyright © Italian Federation of Cardiology. Unauthorized reproduction of this article is prohibited. Chemotherapy cardiotoxicity: cardioprotective drugs and early identification of cardiac dysfunction Daniela Di Lisi a , Giuseppe Leggio a , Giuseppe Vitale a , Salvatore Arrotti a , Rosanna Iacona a , Riccardo Maria Inciardi a , Domenico Nobile a , Francesca Bonura a , Giuseppina Novo a , Antonio Russo b and Salvatore Novo a Background Chemotherapy cardiotoxicity is an emerging problem and it is very important to prevent cardiac dysfunction caused by anticancer drugs. The aim of this study was to assess the alterations of the cardiac function induced by chemotherapy in a follow-up of 2 years and to evaluate the cardioprotective role of angiotensin-converting enzyme inhibitors (ACEIs) in the prevention of cardiac dysfunction. Methods A prospective study was carried out using patients with breast cancer (85 women; median age 57 W 12 years) and other inclusion and exclusion criteria. On the basis of treatment, patients were divided into six groups: fluorouracil-epirubicincyclophosphamide, FEC (group A); FEC and trastuzumab (B); trastuzumab (C); FEC and taxotere (D); FEC, paclitaxel and trastuzumab (E); and chemotherapy and cardioprotective drugs (F). Cardiological evaluation including electrocardiogram and conventional echocardiogram with tissue Doppler imaging (TDI) was carried out at T0 (before starting chemotherapy), T1 (after 6 months from the start of chemotherapy) and T2 (2 years after the end of chemotherapy). Results Significant changes in the TDI parameters of systolic and diastolic function were observed at T1 and T2 in all patients. A significant reduction of left ventricular ejection fraction (LVEF) was observed only at T2. In the patients treated with ACEI (F), these changes were less significant than in other groups and they do not have significant changes in the indices of diastolic function. Conclusion TDI is more sensitive than conventional echocardiogram in the early diagnosis of cardiac dysfunction and ACEIs seem to have an important role in the prevention of cardiotoxicity. J Cardiovasc Med 2014, 16:000–000 Keywords: angiotensin-converting enzyme inhibitor, cardiotoxicity, chemotherapy, prevention, tissue Doppler imaging a Department of Biomedicine, Internal Medicine and Specialities (DIBIMIS), Division of Cardiology and b Division of Oncology, University Hospital ‘P.Giaccone’, University of Palermo, Palermo, Italy Correspondence to Giuseppe Leggio, MD, Department of Biomedicine, Internal Medicine and Specialities (DIBIMIS), Division of Cardiology, University Hospital ‘P.Giaccone’, University of Palermo, Palermo 90127, Italy. E-mail: giuseppeleggio1988@gmail.com Received 30 January 2014 Revised 22 September 2014 Accepted 23 September 2014 Introduction Chemotherapy cardiotoxicity is an emerging problem. Some drugs, such as anthracyclines and other biological agents, can cause cardiovascular complications (left ven- tricular dysfunction, heart failure, myocardial ischemia, hypertension, arrhytmias, pericarditis, cardiac tampo- nade). 1 Anthacycline-induced cardiotoxicity has been categorized into acute, early-onset chronic progressive and late-onset chronic progressive. 2 Late anthracycline cardiotoxicity is cumulative, dose related and high dosages can result in congestive heart failure and left ventricular dysfunction. 3 Usually, cardiac damage caused by anthracycline is irreversible (Type I cardiotoxicity). Trastuzumab induces predominantly reversible dysfunc- tion (Type II cardiotoxicity). 4 This classification system does have limitations; for example, trastuzumab, a Type II drug, can trigger irreversible cardiac damage in patients with severe preexisting cardiac disease or potentiate anthracycline Type I cardiotoxicity. In Type I cardio- toxicity, usually pathophysiology is related to cell loss, and in Type II, cellular dysfunction (mitochondrial and protein alterations) underlies the reversible damage. 5 Thus, it is very important that the early diagnosis of left ventricular dysfunction induced by anticancer drugs using tissue echocardiographic parameters [such as tissue Doppler imaging (TDI) and speckle tracking] is more sensitive than conventional echocardiography and the prevention of severe forms of cardiac dysfunction using early cardioprotective drugs [such as angiotensin- converting enzyme inhibitor (ACEI), angiotensin recep- tor blockers (ARBs) and beta-blockers] when subclinical cardiotoxicity has been identified. 6 The aim of this study was to assess the alterations of the cardiac function induced by chemotherapy in a follow-up of 2 years (using conventional echocardiographic parameters associated with tissue Doppler parameters) and to evaluate the protective role of drugs (ACEI, ARBs and beta-blockers) in the prevention of severe forms of cardiac dysfunction. Original article 1558-2027 ß 2014 Italian Federation of Cardiology DOI:10.2459/JCM.0000000000000232 brought to you by C metadata, citation and similar papers at core.ac.uk provided by Archivio istituzionale della ricerca - Università di P