Cardiotoxic effects and myocardial injury: the search for a more precise definition of drug cardiotoxicity

Abstract

Drug-induced cardiotoxicity is a major clinical problem; cardiotoxic drugs may induce both cardiac dysfunction and myocardial injury. Several recent studies reported that cardiac troponins measured with high-sensitivity methods (hs-cTn) can enable the early detection of myocardial injury related to chemotherapy or abuse of drugs that are potentially cardiotoxic. Several authors have some concerns about the standard definition of cardiotoxicity, in particular, regarding the early evaluation of chemotherapy cardiotoxicity in cancer patients. Several recent studies using the hs-cTn assay indicate that myocardial injury may precede by some months or years the diagnosis of heart failure (HF) based on the evaluation of left ventricular ejection fraction (LVEF). Accordingly, hs-cTn assay should considered to be a reliable laboratory test for the early detection of asymptomatic or subclinical cardiotoxic damage in patients undergoing cancer chemotherapy. In accordance with the Fourth Universal Definition of Myocardial Infarction and also taking into account the recent experimental and clinical evidences, the definition of drug-cardiotoxicity should be updated considering the early evaluation of myocardial injury by means of hs-cTn assay. It is conceivable that the combined use of hs-cTn assay and cardiac imaging techniques for the evaluation of cardiotoxicity will significantly increase both diagnostic sensitivity and specificity, and also better prevent chemotherapy-related left ventricular (LV) dysfunction and other adverse cardiac events. However, large randomized clinical trials are needed to evaluate the cost/benefit ratio of standardized protocols for the early detection of cardiotoxicity using hs-cTn assay in patients receiving chemotherapy for malignant diseases.

Role of Cardiac Biomarkers in Cancer Patients

“…Other mechanisms of troponin release, in the absence of a myocardial damage, are normal myocardial cell turnover and cell release of cTn breakdown products (Figure 2). However, it is not clinically possible to distinguish the mechanisms that cause the cTn level to rise from the laboratory result alone [11][12][13][14].…”

Early diagnostic value of high‐sensitivity cardiac troponin T for cancer treatment‐related cardiac dysfunction: a meta‐analysis

“…Because acute myocardial infarction due to myocyte ischaemia and hypoxia could lead to myocardial cell necrosis and destruction of cell membranes and organelles, the release of troponin into the bloodstream can be detected. Possible pathophysiological causes of troponin elevation in patients with CTRCD include 30 excitation/contraction coupling and/or alterations in intracellular calcium homeostasis and/or mitochondrial function, leading to cardiomyocyte dysfunction; altered cardiac pre‐loading and post‐loading conditions; and alterations in extracellular matrix composition 31,32 . The injury in CTRCD begins at the cellular level before abnormal cardiac function.…”

“…Possible pathophysiological causes of troponin elevation in patients with CTRCD include 30 excitation/contraction coupling and/or alterations in intracellular calcium homeostasis and/or mitochondrial function, leading to cardiomyocyte dysfunction; altered cardiac pre-loading and post-loading conditions; and alterations in extracellular matrix composition. 31,32 The injury in CTRCD begins at the cellular level before abnormal cardiac func- tion. The ability of hs-cTnT to accurately identify small changes in troponin concentration (increase or decrease) within a short time period provides greater analytical accuracy and clinical sensitivity for acute myocardial injury and, thus, allows identification of early myocardial injury at the cellular level.…”

Role of Clinical Risk Factors and B-Type Natriuretic Peptide in Assessing the Risk of Asymptomatic Cardiotoxicity in Breast Cancer Patients in Kazakhstan

“…In addition, including biomarkers in the algorithms of CTRCD detection allows for a comprehensive evaluation of cardiac function. Studies have shown that elevated levels of the primary cardiac biomarkers, troponin and B-type natriuretic peptide, are significantly associated with HF and asymptomatic LVD within cancer treatment [18][19][20][21][22][23]. Several new potential biomarkers, such as C-reactive protein (CRP), soluble suppression of tumorigenicity 2 (sST2), galectin-3 (Gal-3), myeloperoxidase (MPO), placental growth factor (PIGF), tumor growth differentiation factor (GDF-15), and microRNAs, hold promise for predicting cardiovascular disease not only in cancer patients but in cases of other chronic diseases [24,25].…”