ABC | Volume 111, Nº5, November 2018

Original Article Souza et al Arterial Stiffness and Cardiotoxicity Arq Bras Cardiol. 2018; 111(5):721-728 Figure 1 – Left ventricular ejection fraction (LVEF) values measured by transthoracic Doppler echocardiography in breast cancer patients before (pre-chemo) and after the fourth cycle of chemotherapy (post-4chemo) in the chemotherapy regimen with doxorubicin combined with cyclophosphamide. p values refer to Wilcoxon test. 75 70 65 60 LVEF (%) Pre-chemo Post-4chemo p = 0.472 * * * * Table 1 – Characteristics of the patients evaluated in the sample Variables n = 24 Age, years 52,33 ± 8,85 BMI, kg/m 2 31 ± 5,87 Smoking 5 (20,8) Alcoholism 4 (16,7) Diabetes Mellitus 3 (12,5) Hypertension 14 (58,3) Resultsexpressedasmean±standarddeviationorn(%).BMI:bodymass index. Results The sample consisted of 24 women, mean age of 52.33 ± 8.85 years, and mean Body Mass Index (BMI) of 31 ± 5.87 kg/m 2 . Approximately 16.7% of the women were alcoholics, and 20.8% were smokers. More than half of them (58.3%) had hypertension, while 12.5% had type 2 diabetes mellitus (Table 1). LVEF mean values obtained through transthoracic Doppler echocardiogram before and after the fourth cycle of chemotherapy were 67.8% ± 3% and 66.0% ± 3%, respectively, and showed no significant difference between the two times (Figure 1). We also did not observe differences in hemodynamic variables among the three periods analyzed (pre-chemo, post-1chemo, and post‑4chemo - all with p > 0.05), in relation to peripheral and central systolic and diastolic BP parameters, mean BP, pulse pressure, heart rate, pulse pressure augmentation, systolic volume, cardiac output, total vascular resistance, cardiac index, augmentation pressure, reflection coefficient and augmentation index (Table 2). PWV, a variable that correlated most with arterial stiffness, did not show a statistically significant difference among the three periods analyzed, with p = 0.507 (Figure 2). Discussion Since the 1970s, chemotherapy with doxorubicin is known to be related to an increase in the prevalence of HF. 15-17 To a lesser extent, but used in high doses, cyclophosphamide has also been shown to be toxic to the cardiovascular system. 18 Currently, the main guidelines for chemotherapy of the most prevalent types of cancer, especially breast cancer, recommend the combination of these agents. 19,20 Several studies have shown a large increase in the incidence of cardiovascular changes following cancer chemotherapy. Frequently, such changes are only clinically observed months or years after the use of these medications. 2,8,12 The protocol for adjuvant and neoadjuvant treatment of breast cancer at the institution where the research was performed is based on the doxorubicin and cyclophosphamide regimen. The use of other regimens with taxane and 5-fluorouracil can be applied as an adjuvant and as a neoadjuvant; in our study, we chose not to include patients taking these drugs, because the incidence of HF is lower when compared to anthracyclics (5% to 35% of cases vs. 2% to 10%). 6,7 Also, the number of patients using 5-fluorouracil-doxorubicin-cyclophosphamide, or 5-fluorouracil-epirubicin-cyclophosphamide in the institution is lower when compared to the AC regimen. As the incidence of cardiovascular toxicity with the use of trastuzumab alone is low in prospective clinical studies, ranging from 1% to 4%, commonly reversible if detected early, and with a good response to clinical treatment, we chose to exclude patients on their use. 21,22 According to data from the World Health Organization (WHO), oncological diseases are currently the second largest cause of death in the world. 23 The continuous therapeutic developments of the last decades allowed an increase in the survival of these patients. The adverse effects caused by chemotherapy, especially in the cardiovascular area, have become an important cause of morbidity and mortality in this population. It is estimated that the mortality rate among oncological patients who develop some 723