Should Cardiac Biomarkers Play a Role in Evaluating Patients Undergoing Chemotherapy?

Antineoplastic agents have progressed in a remarkable way over the last years. The introduction of targeted therapies has increased the cure and remission rates in some cancers and has even turned certain cancers into chronic diseases that can be controlled or managed for months or years.  However, chemotherapy-induced cardiotoxicity is a growing problem in the setting of clinical oncology. There is an emerging group of patients who survive cancer only to experience significant cardiac side effects due to these therapies.  Cardiotoxic side effects can have a significant impact not only on the quality of life of these patients, but also on their prognosis. Chemotherapy-induced cardiotoxicity usually presents after completion of treatment (days to years later), therefore early detection of those at risk is a primary goal for both cardiologists and oncologists.

Currently there are no clinical parameters that accurately predict the risk of cardiotoxicity.  The clinical manifestations range from minor ECG changes to MI and cardiomyopathy.  Measurement of the left ventricular ejection fraction (LVEF) is a robust predictor of outcome, and is the variable used historically to evaluate cardiac systolic function at baseline and during chemotherapy. The evaluation of LVEF is commonly done through echocardiography. We can also use sensitive tests to measure cardiac biomarkers such as troponin to reveal  myocardial damage produced by chemotherapy.  Several studies demonstrate that these noninvasive, easily performed measurements recognize myocardial alterations and can predict later decrease in the LVEF.

In our recent study we demonstrated that elevations in plasma troponin detected with a high-sensitivity assay predict the later occurrence of chemotherapy-induced cardiotoxicity.  Both troponins I and T were elevated within 3 months of treatment in most of our patients, suggesting that myocardial damage is frequent in patients undergoing chemotherapy.

Currently, there are guidelines for monitoring chemotherapy-induced cardiotoxicity in children treated with anthracyclines. In the adult population, the American Heart Association recommends close monitoring of cardiac function during anthracycline therapy, although it does not specify the methods, thresholds, or intervals that should be utilized during follow-up.  Echocardiography has been the preferred method of monitoring cardiac function. We advocate the use of the cardiac echo combined with measurement of cardiac troponin using  a high- sensitivity assay.  The use of these predictive markers may help identify patients who would benefit from closer cardiac monitoring among those undergoing chemotherapy with especially cardiotoxic drugs like anthracycline and trastuzumab.  As the field moves toward personalized antineoplastic therapeutic strategies, should cardiac markers be included in the regimen to guide earlier initiation of cardioprotective medical therapies, monitoring of the progression of cardiac damage, and/or the use of less cardiotoxic anticancer drugs?