How to monitor cardiac toxicity of chemotherapy: time is muscle!

Cancer and cardiovascular (CV) disease are the leading causes of death in the western world. The increasing age of the western population and the improved global cancer survival, due to ongoing advances in anticancer treatments, point to further increases in the CV burden in cancer survivors as a consequence of exposure to cardiotoxic drugs. Since it is not desirable to improve cancer survival at the price of increased CV mortality and morbidity, more and more cardio-oncological papers are seeking methods to enhance the early diagnosis of cardiotoxicity. Before being able to determine which tests are best at identifying cardiotoxicity in a quick, accurate and prognostically relevant way, we have to understand how cardiotoxicity has been defined. Histological proof of cardiotoxicity remains the diagnostic gold standard, but its correlation with functional cardiac status is unclear, and additional practical limitations make it unsuitable for detecting cardiotoxicity. Historically, left ventricular ejection fraction (LVEF) was chosen as the parameter for monitoring/identifying cardiotoxicity in clinical practice with proven impact on prognosis. LVEF expresses global LV systolic function, it correlates well with functional status for the majority of the population, and several well studied methods can measure LVEF with acceptable to high accuracy. However, its limitations have been well established over the last 10 years, ranging from methodological through mathematical to statistical ones. Cardiotoxicity was first defined by Schwartz et al 1 in an anthracycline treated population, using multiple gated acquisition (MUGA) scanning to determine LVEF during and after anthracycline treatment. The diagnosis of cardiotoxicity was fulfilled in the case of an absolute 10% drop in LVEF or a decrease to below 50% in patients with baseline LVEF >50%, or an absolute 10% drop in LVEF or a drop below 30% in patients with baseline LVEF <50%. Several years later, the Cardiac Review and Evaluation Committee (CREC) …