Cardiac troponin is the most effective translational safety biomarker for myocardial injury in cardiotoxicity

There is an overwhelming weight of evidence that certifies cardiac troponin (cTn) as the preferred, defacto, translational, safety biomarker for myocardial injury in cardiotoxicity. As well as being the gold standard for cardiac injury in man, it has been widely used for clinical assessment and monitoring of cardiac toxicity in humans being treated for cancer. Furthermore, several dozen preclinical published studies have directly confirmed its effectiveness in laboratory animals for assessment of cardiotoxicity. It is gradually being reverse translated from human into animal use as a safety biomarker. Its use is especially merited whenever there is any safety signal indicating potential cardiotoxicity and its required inclusion as a routine biomarker in preclinical safety studies seems on the horizon. There are some considerations that are unique to use of cTn assays in animals. Lack of awareness of these has, historically, significantly inhibited the introduction of cTn as a safety biomarker in preclinical toxicology. Firstly, cross-species reactivity is usually but not always high. Secondly, there is a background of cardiac injury that needs to be controlled for, including spontaneous cardiomyopathy in Sprague Dawley rats, and inappropriate blood collection methods. Also, there are faster kinetics of clearance in rats than for humans. Also, coincident muscle injury is frequent with cardiotoxicity and requires a skeletal muscle biomarker. Because cTn assays were developed for detection of gross cardiac necrosis, such as occurs with myocardial infarct, the more sensitive assays should be used for preclinical studies. However, analytic sensitivity is higher for standard preclinical studies than for clinical diagnostic testing because of use of concurrent controls and use of batch analysis that eliminates interassay variability. No other biomarker of myocardial injury comes close to cTn in effectiveness, including CK-MB, LDH-1 and 2, myoglobin, and FABP3. In addition to the use of cTn for monitoring active myocardial degeneration, there is growing evidence that measurements of brain natriuretic peptide (BNP) may be effective for monitoring drug-induced left ventricular dysfunction.