The development of tools for the early identification of patients at greater risk of cancer therapy-related cardiac dysfunction and heart failure is an area of active research in cardio-oncology. It has been recently showed that the traditional definition of cancer therapy-related cardiac dysfunction as a reduction in left ventricular ejection fraction with traditional echocardiography might not be sensitive enough to detect myocardial damage when it can be still reverted.
Aim: To detect early changes of new echocardiographic measures in patients treated with epirubicin; to investigate whether there is a relationship between these new echocardiographic measures and biomarkers associated with the development of cardiotoxicity. Their prognostic value as early markers for the development of cancer therapy-related cardiac dysfunction will be assessed.
Methods: Breast cancer patients free from previous cardiovascular disease and exposed to epirubicin will be recruited. Patients will receive both conventional and layer-specific myocardial 2D strain echocardiography at baseline, at the completion of chemotherapy as well as 3, 6 months and 1 year after the end of chemotherapy. Peak systolic dispersion will be also assessed. Biomarkers (high-sensitivity troponin, Nt-pro-BNP and BNP) will be assessed before every cycle of the regimen, at the completion of chemotherapy as well as 3, 6 months and 1 year after the end of chemotherapy.
Expected results: Changes in regional Layer-specific Myocardial Strain will develop by the completion of the regimen, and they will be significantly associated with later development of left ventricular dysfunction during the 1 year follow up. Such early modification in layer-specific regional strain will be associated with an early increase of biomarkers. If so, the integration of these new tools in clinical practice might facilitate the use of targeted cardioprotective strategies to prevent the subsequent development of heart failure.
A critical factor for cardiovascular healthcare providers is that most of the breast cancer survivors have higher CV disease (CVD) risk than non-cancer controls. Indeed, CV death is the second largest cause of death after breast cancer itself. Collectively, there has been a paradigm shift from cancer as a terminal illness to a chronic condition with CVD risk. Moreover, chemotherapies themselves might be associated with the development of CVD. In particular, anthracycline-induced cardiotoxicity is still a significant problem that compromises the quality of life and overall survival of cancer patients. However, recent findings demonstrate that this form of cancer therapy-related cardiac dysfunction (CTRCD) is mostly reversible when early detected and with a prompt therapeutic strategy, whereas it is largely irreversible when left ventricular (LV) dysfunction is established. Indeed, probably, anthracycline-induced cardiotoxicity is a continuous phenomenon, from cellular to clinical stage, starting with myocardial cell injury, followed by progressive LV ejection fraction (LVEF) decline and, potentially, overt heart failure (HF). The current standard for monitoring cardiac function (periodic assessment of LVEF), detects cardiotoxicity at a late stage when a significant impairment has already occurred, precluding the chance of effectively prevent and treat its development. Therefore, it has been recently tried to identify new methods that can help identifing earlier damage caused by chemotherapy. Biomarkers, particularly cTn, have demonstrated a high negative predictive value for the development of LV dysfunction. However, their accuracy is also limited by the fact that there are not validated cut-off values for the definition of CTRCD, nor the most appropriate timing for carrying out serial determinations is known. At the same time, non-standard echocardiographic measures that could discriminate even subtle and earlier alteration of LV systolic function have been tested. Among these, recent evidence suggests that the introduction of LV strain analysis by speckle tracking may be of help. However, there are still no reliable data in the literature that correlate the increase in biomarkers with regional layers-specific changes in LV myocardial strain and prognosis in the long term of patients undergoing chemotherapy.
The present project aims to enroll patients without previous CVD and candidates for therapy with epirubicin. These patients will undergo a baseline evaluation including the determination of biomarkers and myocardial strain, in particular the regional layer-specific strain which has been shown to intercept LV dysfunction early in other case series. These assessments will be repeated early during the follow-up, which will last one year. In this time interval, from the previous literature, 98% of the traditionally defined CTRCD should develop. Our investigation will allow us to evaluate the kinetics of biomarker release and their possible association with alterations of the regional layer-specific strain and PSD. The possible correlation of these data with the subsequent development of CTRCD will then be evaluated. Therefore, for the first time in the literature to our knowledge, the predictive power of associating the determination of biomarkers with myocardial function changes defined by regional layer-specific strain and PSD will be defined.
A particular strength of this study would be to define time points (determination of biomarkers before each chemotherapy cycle and one day, three, six, and twelve after the completion of chemotherapy and echocardiograms after 1 day, three, six, and twelve months after the completion of chemotherapy) which are compatible with clinical practice.
The use of biomarkers and regional layer-specific LV strain might become a new standard to identify high risk patients who should start early treatment with ACE-inhibitors and beta blockers to prevent anthracycline-related LV dysfunction and cardiac events. Indeed, inverse relationship in terms of LVEF improvement has been found between the time interval from the end of chemotherapy and the beginning of HF therapy, with no complete recovery when CV therapy is started 6 months after the end of chemotherapy 1.Therefore, since reversibility is a matter of time and depends on early diagnosis, the implementation of standard means currently adopted in clinical practice is highly recommended.
1 10.3389/fcvm.2020.00026