ABC | Volume 111, Nº5, November 2018

Original Article Souza et al Arterial Stiffness and Cardiotoxicity Arq Bras Cardiol. 2018; 111(5):721-728 Arterial Stiffness (AS) is characterized by the reduction of the arteries elastic properties due to intrinsic structural or functional changes. 9 Aging is a normal evolutionary factor for vascular stiffening, and can be accelerated by several factors, such as diabetes and hypertension. 10 Several studies have related the increase in AS with the progression of cardiovascular diseases. 3,5,11 The early increase in AS can be estimated mainly through the evaluation of the Pulse Wave Velocity (PWV) obtained from indirect imaging or hemodynamic methods. 3,12,13 Because cardiovascular changes are observed in some patients on doxorubicin, and AS measurement allows the detection of the onset and progression of cardiovascular disease, this study is warranted because it aims to estimate AS, based on PWV measurement, through oscillometric evaluation of the brachial artery, in patients with breast cancer in the initial phases of chemotherapy with doxorubicin combined with cyclophosphamide (AC regimen). In addition, it proposes to check if there is a correlation between AS and the values of Left Ventricular Ejection Fraction (LVEF), an altered condition in patients with cardiotoxicity due to chemotherapy. Methods Thisisaprospectiveandlongitudinalstudywithaconvenience sample. Twenty-four women aged over 18 years with breast cancer and indication of at least four cycles (every 3 weeks) of adjuvant or neoadjuvant chemotherapy based on the AC regimen (at doses of 75 mg/m 2 for doxorubicin and 600 mg/m 2 for cyclophosphamide in each cycle, totaling 300 mg/m 2 and 2,400 mg/m 2 for doxorubicin and cyclophosphamide, respectively) were followed. The recruitment took place in an Oncology Outpatient Clinic of a High Complexity Unit in Public Oncology of the city of Belo Horizonte (state of Minas Gerais), from July 2016 to December 2017. The following were excluded: pregnant and lactating women; patients with previous history of chemotherapy or radiotherapy; pre-chemotherapy assessment showing abnormal left ventricular systolic function (LVEF < 50%) evaluated by Doppler echocardiography; history of/or active heart disease; moderate to severe hepatic or renal dysfunction; brain-degenerative diseases requiring caregiver’s action; and those in use of other chemotherapeutics other than the AC regimen in the treatment of breast cancer. Randomization took place in an outpatient basis, under clinical evaluation by a cardiologist with experience in the area. Subsequently, patients underwent an echocardiographic study, according to themethodology proposed by Campos‑Filho et al., 14 to evaluate cardiac parameters that could contraindicate participation in the study and also to monitor the cardiac function at different treatment times of chemotherapy, as suggested by current guidelines. 5,7 Following these procedures, patients were referred for chemotherapy with doxorubicin and cyclophosphamide in the same hospital. Brachial artery AS measurement was performed using the non-invasive device Mobil-O-Graph® 24h PWA (IEM, Germany) through oscillometric measurements on the upper limb. The device has a device for Blood Pressure (BP) measurement and provides measures of PWV, systolic and central diastolic pressure, and augmentation index , which are used as an estimate of AS. This device was validated for use in scientific research by the European Society of Hypertension . 13 Measurements were made in the contralateral upper limb on the side affected by the tumor, seeking to exclude the influence of axillary dissection surgery and consequent lymphedema. After measuring the circumference of the limb and choosing the appropriate cuff, the device was positioned similarly to procedures defined by guidelines of cardiology societies. 7 Mobil-O-Graph® 24h PWA is able to offer a number of useful results of the cardiovascular condition of the evaluated patient, because the BP and PWV measurements are correlated with the weight, height and age data previously provided by the HMS Client-Server data management software. Follow-up chronology was implemented withmeasurements of hemodynamic parameters by Mobil-O-Graph® 24H PWA at three different times: (1) prior to chemotherapy, when measurements of the hemodynamic parameters through the oscillometric method were taken 15 minutes before the beginning of chemotherapy infusion; (2) post-1chemo, measured up to 30 minutes after intravenous (IV) infusion of the first cycle of the AC regimen; there was a variation of 45 to 90 minutes in the chemotherapy infusion; and (3) post‑4chemo, measured up to 30 minutes after IV infusion of the fourth cycle of the AC regimen; the time interval from the start of chemotherapy to its completion was 80 to 90 days. After 1 week of the fourth chemotherapeutic cycle, the patient underwent a new clinical-cardiological evaluation and an echocardiographic study for LVEF analysis and for comparison with the value before the first cycle. The results of all the variables that the Mobil-O-Graph® 24H PWA instrument provided were tabulated and submitted to statistical treatment among the three measures of the patients studied. The protocol of this study is in accordance with the Declaration of Helsinki, having been released by the Research Ethics Committee of the institution, and all the patients evaluated signed the Free Informed Consent Form (FICF). Statistical analysis The variables underwent the Shapiro-Wilk normality test and were presented as mean ± Standard Deviation (SD), in case of normality, or as median (Interquartile Distance - DI - which is the difference between the third and the first quartiles). Categorical variables were expressed in frequency. The three measurements provided by the device were expressed as mean ± SD. In the comparison between the three moments (pre-chemotherapy, soon after the first cycle of chemotherapy, and after the fourth cycle), we adopted the analysis of variance for repeated measures, with the sphericity check, or Friedman test. The comparison of measurements between two moments was performed by the Wilcoxon test for paired samples, including post hoc analysis. The analysis was developed in the free software R, version 3.3.2, with a significance level of 5% being adopted. 722