Improving cardiovascular outcomes for cancer patients and survivors: focus on novel biomarkers for risk stratification

Cancer and cardiovascular disease (CVD) are the two leading causes of morbidity and mortality worldwide. In Australia alone, cancer and CVD accounted for 57.6% of deaths between the years 2011 – 2020. The most updated financial report suggests that an estimated $11.7 billion dollars (2018-2019) was spent on direct cancer management, and these numbers will only increase with rising cancer diagnoses as the population ages and grows. Simultaneously, cardiovascular disease accounted for an estimated 10.4 billion dollars (8.9%) of total disease expenditure in the Australian health care system in 2015-2016 and CVD was associated with over 1.2 million hospitalisations in 2017-2018. Advances in cancer treatment have reduced cancer-related mortality, however, cardiovascular sequelae as a result of cancer treatments has become a more prominent modifier of quality of life and overall survival rate. Cancer therapy-related cardiovascular toxicity (CTR-CVT) can occur in approximately 5 – 25% of cancer survivors depending on the anti-cancer regimen. Furthermore, it is associated with significant negative implications for long term survival and can impose additional economic burden to the patient and the healthcare system. This has given rise to the dedicated sub-specialty of Cardio-Oncology, an emerging field of study in Australia, that aims to detect, prevent and treat various cardiovascular complications arising from cancer treatments in patients living with, through and beyond cancer. Major underlying causes of long-term cardiovascular (CV) morbidity, mortality with associated healthcare costs in cancer patients, is engendered by several issues, including: 1) methods used to predict and detect early onset cardiac injury prior to development of cardiac dysfunction remain suboptimal, 2) lack of understanding of cardiotoxic mechanism(s) of chemotherapies, and 3) no proven cardioprotective therapies for the broad spectrum range of anti-cancer agents. Detection of early onset cardiac injury is complicated for multiple reasons: a) the large number of anti-cancer treatments, with different mechanisms of actions, b) lack of sensitivity of diagnostic tests and, c) pre-existing concomitant cardiovascular risk factors prior to cancer. While the current methods of detection using echocardiography have been shown to predict/detect obvious cases of cardiotoxicity, they suffer from a lack of sensitivity and reliability to detect early changes in myocardial dysfunction seen in CTR-CVT. As early detection and treatment of CTR-CVT is pivotal in reversing cardiac dysfunction leading to functional recovery of the heart, more sensitive measurements of cardiac injury are required to improve patient outcomes. A complimentary method for early detection of CTR-CVT is with the use of biomarkers. Biomarkers can play important roles in 1) identification of patients at high-risk of CTR-CVT prior to initiation of therapy; 2) complementing imaging modalities during active therapy to detect subclinical disease; and 3) potentially allowing individualized preventive therapy. It is noteworthy that currently, there is a strong focus on the cardiotoxic effects of one class of chemotherapy (anthracyclines) and Trastuzumab; and therefore, potential common mechanism(s) of cardiotoxicity with other classes of chemotherapeutics has not been investigated.