Anthracyclines (ACT) are effective antineoplastic agents with a broad antitumour spectrum but they can cause cardiotoxicity. This may be acute but also manifest as late causing delayed cardiotoxicity. This is the major limiting factors in the use of these agents. Serial cardiac monitoring prior, during and after treatment is required and left ventricular ejection fraction (LVEF) is the predominant parameter for cardiac dysfunction detection but it appears an unreliable guide.
Despite several biomarkers has been prosed none of this appears a reliable tool to make diagnosis and is able to predict heart damage. Cardiovascular Magnetic Resonance (CMR) has been used to detect cardiac damage. However, the late gadolinium enhancement technique to detect focal fibrosis failed in the majority of the case. ACT cause more likely diffuse myocardial changes missed by this technique. Advanced sequences by CMR (mapping technique) allow now to identify and quantify diffuse fibrosis and oedema in a more robust and reproducible way. Multi-modality approaches may therefore add benefit to investigate the toxic effect of ACT and also guidelines are moving through a multiparametric approach
Accordingly, we sought to perform a serial cardiovascular monitoring in haematological patients treated by ACT with a systematic and multiparametric approach combing clinical and imaging data to detect the earlier marker of cardiac damage able to predict LVEF reduction at one year.
Patients affected by Hodgkin and non-Hodgkin lymphomas, acute myeloid and lymphoblastic leukemia, aged>18 years, with indication to chemotherapy regimen including ACT will be recruited. Only chemotherapy and radiotherapy naïve patients will be recruited excluding patients with cardiovascular disease.
All subjects will be undergone medical assessment, electrocardiogram, echocardiogram with strain evaluation and CMR with mapping technique prior chemotherapy administration, at the end of chemotherapy and after one year.
The anthracycline (ACT) cardiotoxicity has been extensively studied over the last decade however a lot of unresolved questions still remain. The most used parameter to detect cardiotoxicity, both in clinical practice and research, is the left ventricle ejection fraction (LVEF) which has several limitations. Accordingly, a better marker is required, able to detect changes at the earliest possible stage. All the works performed so far, looking for new biomarker, focused on a single test for serial monitoring (ie a blood biomarker or a parameter derived by echocardiography or cardiovascular magnetic resonance), while others performed a multimodality approach but limited to cancer survivors in cross-sectional study.
To our knowledge, this study is based for the first time on a different approach. The idea is to combine the information provided by serial monitoring in subjects treated by ACT using existing techniques but in a new fashion. We will perform for the first time serial cardiovascular monitoring using the best technology available to guarantee robust and higher reproducibility results.
In this observational prospective study we can track changes over time and we will able to detect the earlier change able to predict later cardiac function changes. Furthermore, this approach promises to overcome the lack of association between results from clinical data, blood biomarkers and imaging data. The systematic and serial evaluation of patients with a comprehensive evaluation aim to describe the cascade of events and to track changes over time picking-up the earlier change from the baseline evaluation.
The network proposed among cardiologists, hematologists and radiologists will guarantee a multidisciplinary approach in order to link and interpret results from different field providing physiopathological insight. All the technologies required by the study are already available, the set-up is in place accordingly the feasibility of the study is guarantee.