ABC | Volume 112, Nº3, March 2019

Review Article Jorge et al Imaging for chemotherapy-related ventricular dysfunction Arq Bras Cardiol. 2019; 112(3):309-316 dysfunction in adult cancer patients, recommending the use of RNV or CMRI in cases where echocardiography is not available or technically feasible, for example, in cases with inadequate ultrasound windows. 38 In addition to evaluating systolic function, RNV has demonstrated value in following diastolic function in patients exposed to cardiotoxic medications. Radionuclide ventriculography versus echocardiography RNV was more sensitive than echocardiography in detecting early decreases in LVEF. 39,40 However, in these small studies, there was a high incidence of CTX (over 48%) without long-term follow-up. This limitation did not allow for correlations to be drawn with HF incidence. In a study of breast cancer patients who received ANT and TZU, measurements of LVEF by 3D ECHO and RNV were comparable, with CMRI used as a reference. 23 A document titled “American Society of Echocardiography Expert Consensus Statement for Multimodality Imaging Evaluation of Adult Patients During and After Cancer Therapy” 8 recommends the use of 2D ECHO or 3D ECHO for evaluating LVEF before, during, and after CT. In the case of inadequate image quality, the use of CMRI is recommended; RNV is not mentioned as a routine method. The specific availability of each service certainly interferes with the choice of method. There are currently new scintigraphic methods with other markers of early myocardial injury, 35 which are capable of subclinically detecting LV dysfunction and which could predict the development of subsequent LV dysfunction or HF, such as sympathetic neural imaging with the 123 I- meta -iodobenzylguanidine ( 123 I- m IBG) technique, imaging of cell death ( 111 In-antimiosina), targeted therapy imaging ( 111 In-TZU), and molecular metabolic imaging of PET. All of these techniques have yet to be clinically validated for use in this CTX situation. Studies with the adrenergic marker of neuronal integrity 123 I- m IBG carried out in patients using ANT demonstrated that scintigraphy with m IBG is capable of identifying patients with a higher risk of CTX with great accuracy. 41 Cardiac magnetic resonance imaging Functional evaluation (cine MR and tagging/strain) CMRI is the gold standard evaluation of LVEF volumes, using the technique of cine MR with quantification by Simpson’s method. Its routine utilization is limited by availability and cost. 42,43 In addition to accurately evaluating left and right ventricular function, CMRI can identify other probable causes associated with cardiomyopathy, such as myocardial invasion of the tumor, amyloidosis, sarcoidosis, myocarditis, and atherosclerotic coronary disease. CMRI should always be considered the first step before endomyocardial biopsy. 8 Draft et al. 44 detected subclinical abnormalities in geometry and ventricular function, such as a significant increase in final systolic volume, decreased LVEF and increased average circumferential strain in patients receiving low to moderate doses of anthracyclines. These markers are not usual criteria for CTX and the relation with prediction of future events is unknown. Armstrong et al. 45 also detected subclinical cardiac dysfuntion using CMRI, analyzing LVEF and LV volume. No study of CMRI to date has demonstrated that alterations in myocardial function indexes after CT with ANT were predictors of subsequent CTX or HF. An ongoing observational study is assessing whether LV function measured by CMRI in patients using ANT, with or without TZU, will be able to predict a decrease in LVEF in 24 months. 46 According to Plana et al . , 8 CMRI should be used to confirm alterations in LVEF reported by other techniques or when there is a conflict between measurements from different techniques. This is only justified in the event that there is a plan to modify or interrupt CT. It is of little interest to use CMRI for diastolic function analysis due to the fact that its accuracy is similar to that of echocardiography. 47,48 There are few studies on the evaluation of myocardial strain by CMRI for evaluating CT-related CTX. In the trial by Draft et al., 44 there was an early increase in midwall circumferential strain, after a month of therapy with ANT, associated with subclinical abnormality in ventricular function, demonstrated by a decrease in LVEF evaluated by CMRI. It is necessary to determine if these markers are associated with cardiovascular events in survivors of cancer. Tissue characterization (myocardial enhancement/T1 mapping/T2 mapping) Myocardial tissue characterization of CTX dates back to the 1980s, when necropsy and biopsy studies revealed that myocardial inflammation and cardiomyocyte edema are early findings of CTX, which occur prior to reduced myocardial function, as opposed to myocardial fibrosis, which is a late finding. 49,50 In addition to its functional evaluation, CMRI is capable of performing morphological and tissue evaluation in a qualitative (visual) and quantitative manner, as percentage of muscle affected. 51 Myocardial interstitial injuries may or may not be reversible, depending on different factors which include the degree of interstitial fibrosis. In this manner, CMRI is able to establish the differential diagnosis between reactive, infiltrative, and scar fibrosis. 52 It is possible to evaluate CTX on the tissue level with early and late enhancement techniques. 52 The main disadvantage is that, in the large majority of subclinical disease cases, there is no visually detectable fibrosis to be quantified and this technique is negative. T1 mapping has been validated for detection of interstitial fibrosis not detected by late enhancement techniques, and the results are informed through the quantification of myocardial relaxation time in milliseconds. 53 During postcontrast, the lower the myocardial T1, the higher the degree of interstitial fibrosis. T1 mapping has shown to be an independent predictor of CTX in patients treated with ANT who were followed for a period of 3 years. 54 Extracellular volume (ECV) fraction which indicates the expansion of interstitial space corrected by hematocrit was also a strong imaging biomarker. 54 T2 mapping is responsible for the quantification of cardiomyocyte edema, and it assists in the characterization of acute, subacute, or chronic damage. 55 The results of T2 mapping are also represented by time in milliseconds. A study with 9 patients who received ANT showed that average T2 values > 59 ms were associated with CTX. 56 312