Cardioxicity Assessment Methods

Various diagnostic exams are used in the assessment of cardiotoxicity. These exams include Electrocardiogram (ECG), Echocardiography, Tissue doppler imaging (TDI), Radionuclide angiocardiography (MUGA), Cardiac magnetic resonance (CMR), Endomyocardial biopsy, Serum biochemical indicators, etc. The decision to employ one/ some of these assessment methods over another depends on several factors, including technical and professional resources, financial costs, invasiveness, safety, diagnostic accuracy, reproducibility, feasibility, and patient preferences. However, it should be noted that each method has its advantages and limitations.

For instance, two-dimensional (2D) echocardiography is the most common imaging modality for evaluating patients in preparation for, during, and after a potentially cardiotoxic therapy.

That

is because of its wide availability, reproducibility, versatility, lack of radiation exposure, and safety in patients with concomitant renal disease. However, echocardiography has limitations too. The most notable is the temporal variability in LVEF. Three-dimensional (3D) echocardiography has improved accuracy and reproducibility but may only be available in some laboratories. Tissue Doppler Imaging (TDI) analysis shows high sensitivity for the detection of mild myocardial dysfunction; however, there are significant limitations to the use of TDI technology; TDI measures only the vector of motion that is parallel to the direction of the ultrasound beam, resulting in considerable angle-dependence and signal noise in the data obtained. In addition, TDI measures absolute tissue motion and cannot distinguish between passive and active motion. Finally, ensuring the reproducibility of TDI data is challenging, as small shifts in sample regions can yield significant differences in measurements. Radionuclide angiocardiography (MUGA) has previously been the most widely used imaging modality for the evaluation of LVEF; this use is principally due to its availability, accuracy, and reproducibility, yet limitations include a radiation exposure of approximately 5–10 millisieverts, which is most significant in the pediatric population given increased concern for radiation exposure, and its inability to assess the cardiac structure. Cardiac magnetic resonance (CMR) is the gold standard for detecting cardiotoxicity due to its accuracy, reproducibility, and ability to see subtle changes in cardiac function that may predict cardiotoxicity. Limitations of magnetic resonance imaging include the inability to perform in patients with implanted cardiac devices, claustrophobia, availability, and higher costs than echo and MUGA. Additionally, although endomyocardial biopsy remains the most sensitive and specific method to assess cardiotoxicity by describing the microscopic structural alterations of myocardial tissue, its use is minimal because of the high invasiveness of the procedure. Biomarkers offer a promising alternative solution for the early detection of cardiotoxicity as they overcome the shortcomings associated with imaging. Biomarkers are easier to perform and less time-consuming for patients as it only involves a blood draw. Biomarkers are also more reproducible than imaging since it avoids the issues of load dependency, technical factors, and inter- and intra-operator variability during result interpretation; however, there are discordant data surrounding the utility of biomarkers in the pre-, during-, and post-cancer treatment periods, as they have undetermined predictive value. To respond to these exams’ limitations, currently, a combination of some of these methods is recommended. This assessment generally includes clinical history and physical examination, electrocardiography to determine the cardiac rhythm and detect signs of ischemia, and cardiac imaging, usually transthoracic echocardiography with a complete doppler study.Electrocardiography has always been a fundamental part of cardiovascular assessment among these diagnostic exams due to its simplicity and non-invasive nature. It is worth noting that with the advent of modern signal processing and machine learning techniques, the diagnostic power of the ECG has expanded exponentially.