ABC | Volume 111, Nº5, November 2018

Original Article Souza et al Arterial Stiffness and Cardiotoxicity Arq Bras Cardiol. 2018; 111(5):721-728 leading to the production of superoxide anions and hydrogen peroxide, which saturate the antioxidant systems and react with the cellular structures, mainly in the membranes, causing cytotoxicity. 27 However, recently, some authors have shown that, in addition to already established myocardial dysfunction, vascular alterations resulting from endothelial dysfunction also occur secondary to the use of anthracyclics and can be used as predictors for the cardiovascular toxicity induced by these agents. 5,28 These changes may occur early, 29 and themechanism proposed for these vascular changes is also related to the production of free radicals, with consequent cell death, or changes in the production of vasoactive endothelial factors. 2,8,30 Some authors have already proposed the use of clinical tools to assess the vascular status of individuals undergoing antineoplastic therapies with anthracyclic drugs. 3,11,31 These vascular changes could also justify an increase in the incidence of systemic arterial hypertension, atherosclerosis, and thromboembolic events in patients after chemotherapy. 11,32,33 Early detection of dysfunctions in the vascular system is always difficult when non-histochemical methods are used, and it appears to develop from endothelial dysfunction, leading to progressive vascular remodeling. 28 In addition, vascular changes could contribute to the increase of the preload and, consequently, to decrease of the cardiac output. Thus, in addition to direct myocardial damage, vascular alterations could, at least in part, be related to the decrease in LVEF in patients undergoing chemotherapy. Several studies have tried to find early markers that can predict the occurrence of these changes in patients on chemotherapy with potential cardiovascular toxicity and, consequently, to detect patients at risk. Currently, LVEF measurement by transthoracic Doppler echocardiogram is considered the main tool to monitor myocardial dysfunction induced by chemotherapy, and is used in several follow-up protocols. 7,34,35 LVEF can also be measured by other techniques. Drafts et al., 11 in a study involving 53 patients who received anthracyclic chemotherapy, showed that changes in LVEF can be detected within 30 days of the beginning of chemotherapy sessions. 11 However, these authors, in addition to using larger sampling, applied more accurate techniques, involving magnetic resonance imaging for the early detection of changes in ventricular volumes, compared to the classic Doppler echocardiogram routinely used in cancer treatment services and also in our study. Although other studies have shown a reduction in LVEF in patients at different times of treatment with these agents, our study was not able to show a significant reduction in LVEF between the values measured before the beginning of chemotherapy and in the post-4chemo. This fact may be due to the short period of patients follow-up, which does not allow the demonstration of a clinical change through this method - although structural and molecular microalterations have been shown early in this profile of patients, in the first months after treatment. 3,11,12 There are studies suggesting that most cardiovascular alterations occur in the early stage, from the third month after the end of chemotherapy. 2,12 Furthermore, because it is a pilot study, the reduced sampling may have contributed to this result. The generic term “arterial stiffness” refers to changes in arterial mechanical properties, in response to acute or chronic phenomena, resulting in atherosclerosis and endothelial dysfunction, and correlating with increased cardiovascular morbidity and mortality. 9 Currently, the best way to estimate AS is by measuring the PWV, obtained through the measurement of the time required for a wave formed by vascular distension to travel a certain distance between two points of an arterial segment. 9 Thus, the greater the values of the PWV, the greater the AS. Some techniques do it with imaging tests, such as ultrasound techniques and magnetic resonance imaging with great precision. However, non-invasive devices, coupled with computerized systems, have been increasingly used for AS measurements. 12 AS has been shown to be an early marker of cardiovascular diseases. A 2010 study showed, for the first time, a significant increase in aortic artery PWV, measured by magnetic resonance imaging, in patients after 4 months of chemotherapy with anthracyclics. 3 In 2013, the same methodology was applied to patients in earlier stages of the same chemotherapy regimen, showing that it is possible to observe changes in PWV only 1 month after the administration of these agents. 11 Despite the relevance of these studies in the predictability of AS changes in patients receiving anthracyclics, they apply methods that demand higher costs and specialized professionals for their technical performance. From 2010 onwards, portable devices appeared that were capable of simple estimation of AS of the brachial artery through oscillometric measurements of the upper limb, providing several hemodynamic data, which may be predictive markers of cardiovascular changes, such as PWV, augmentation index and cardiac index. 13 Since this is an easy-to-use methodology, several studies have evaluated the potential of increased AS as a marker for cardiovascular diseases in various clinical conditions. 36,37 Clinical studies have confirmed the validity of this instrument, which uses several algorithms to obtain hemodynamic variables such as PWV, which is the gold standard for assessing AS. 9,13 With the same equipment, it is possible to measure central BP and other variables, which can be used to estimate arterial stiffness, but they are influenced by pathophysiological conditions, drugs and age, which make them less reliable. 38,39 Due to the practicality of estimating AS through this method, our study proposed to evaluate the application of this methodology and correlate it with the data obtained by the LVEF through Doppler echocardiogram. The use of this tool could simplify the monitoring of cardiovascular toxicity induced by chemotherapy, since the use of Doppler echocardiography, as is routinely done for this purpose, is a method that requires higher cost, a qualified medical professional, and scheduled appointment at a specific time and place. This difficulty of access could reduce the guarantee of cardiotoxicity monitoring in patients who underwent chemotherapy. In our study, all patients were monitored by this system at three different times (immediately before and after the first and fourth cycles of chemotherapy). In contrast to what was observed in other studies, which made these measurements early during chemotherapy, mainly by imaging tests, 3,11 we were unable to show any significant statistical difference in the parameters evaluated at different times. 725