Use of biomarkers for the assessment of chemotherapy-induced cardiac toxicity

Abstract

Objectives To review the evidence for the use of various biomarkers in the detection of chemotherapy associated cardiac damage. Design and methods Pubmed.gov was queried using the search words chemotherapy and cardiac biomarkers with the filters of past 10 years, humans, and English language. An emphasis was placed on obtaining primary research articles looking at the utility of biomarkers for the detection of chemotherapy-mediated cardiac injury. Results Biomarkers may help identify patients undergoing treatment who are at high risk for cardiotoxicity and may assist in identification of a low risk cohort that does not necessitate continued intensive screening. cTn assays are the best studied biomarkers in this context and may represent a promising and potentially valuable modality for detecting cardiac toxicity in patients undergoing chemotherapy. Monitoring cTnI levels may provide information regarding the development of cardiac toxicity before left ventricular dysfunction becomes apparent on echocardiography or via clinical symptoms. A host of other biomarkers have been evaluated for their utility in the field of chemotherapy related cardiac toxicity with intermittent success; further trials are necessary to determine what role they may end up playing for prediction and prognostication in this setting. Conclusions Biomarkers represent an exciting potential complement or replacement for echocardiographic monitoring of chemotherapy related cardiac toxicity which may allow for earlier realization of the degree of cardiac damage occurring during treatment, creating the opportunity for more timely modulation of therapy.

The use of biomarkers in detecting subclinical cardiotoxicity in doxorubicin-based treatment for paediatric patients with acute lymphoblastic leukaemia

“…In 2004, the FDA concluded that TnI is a sensitive, specific and robust biomarker for cardiac damage, allowing the detection and quantification of cellular damage and death [8]. TnI levels have been shown to increase progressively after more AC doses, being associated with a significantly higher risk of left ventricular dysfunction [5]. Given the low elevations of troponin levels that occur after doxorubicin administration, some studies believe that they may represent physiologic variations [8].…”

“…AC-induced cardiac injury is dose dependent and the international recommendations are not to exceed 450-550 mg/m² [3], although even lower doses have led to cardiac damage in certain patients [4]. The gold standard for cardiotoxicity detection is serial echocardiography, used prior to treatment initiation and during the course of chemotherapy [5]. Cardiac biomarkers (troponin T, troponin I (TnI), natriuretic peptides, high-sensitivity C reactive protein, glycogen phosphorylase isoenzyme BB, heart-type fatty acid binding protein (H-FABP), myeloperoxidase, total antioxidant status, circulating microRNAs, creatinine kinase) represent an attractive alternative for the detection of cardiotoxicity and are intensively analysed for many advantages such as being operator-independent, non-invasive and a resource-efficient approach [4].…”

Chemotherapy-induced cardiotoxicity: importance of early detection

“…Many studies have shown that both troponin I and T may detect cardiotoxicity long before any reduction in LVEF has occurred in patients treated with different chemotherapy schedules, containing old and new antitumor drugs [16][17][18]. Additional uses for troponins in patients undergoing anticancer therapy include the following:…”

Early diagnosis of doxorubicin-induced cardiotoxicity:The miRNA way

“…Accumulating evidences indicate that DOX-induced cardiac dysfunction is caused by the perturbation of several physiological pathways, particularly the DNA-damage response pathway [4]. Unfortunately, many of the mechanisms at the base of this phenomenon are not clearly understood yet, and no reliable early toxicity biomarkers are available [5,6]. Cardiac dysfunction insurgence can be assessed by mean of different approaches: angiography, LVEF evaluation by echocardiography, and endomyocardial biopsy.…”

“…The most reliable early marker for detection of heart damage is represented by cardiac troponins, which are routinely used as circulating indicators of cardiac necrosis, a condition characterizing (among other pathologies) myocardial infarction and myocarditis [5,7]. Other possible biomarkers such as tumor necrosis factor α (TNF-α), galectin-3, IL-6, ST2 and sFlt-1 have been evaluated in order to detect subclinical cardiotoxicity after treatment with anthracyclines, but they did not show any clinical value [8].…”