Direct Comparison of the Accuracy and Reproducibility of MUGA, CMR and Echocardiography for Cardiac Function Assessment in Oncology Patients at Risk of Cardiotoxicity

BACKGROUND Cancer is a major worldwide health problem, with around 330 000 new cases diagnosed annually in the UK alone. Improved survival rates due to better treatments have led to an increase in the number of cancer survivors, with over 60% of patients diagnosed expected to survive 5 years. There is also increasing recognition of the cardiotoxic effects of many of the cancer therapies (particularly anthracyclines and Trastuzumab), with subclinical cardiotoxicity found in 18% of subjects receiving anthracyclines of whom one-third have clinically overt heart failure. With trastuzumab, rates of heart failure are even higher, with more than 15% of subjects having to suspend or discontinue treatment. Early detection of cardiotoxicity however permits treatment and (particularly with trastuzumab) recovery of left ventricular function. Patients should therefore have their cardiac function monitored before, during and after treatment (as per published recommendations) to permit early detection and treatment of resultant cardiotoxicity.

The key parameter used for screening for myocardial effects of chemotherapy is the ejection fraction. Cancer therapeutics related cardiac dysfunction is defined by an asymptomatic reduction >= 10% points of the left ventricular ejection fraction (LVEF) to a value <55% or a reduction of LVEF <= 5% to 55% with symptoms of heart failure7. Conventionally this has been measured by nuclear techniques such as Multiple Gated Acquisition Cardiac Blood Pool imaging (MUGA). More recently, echocardiography or cardiac MRI have also been used to measure ejection fraction, as they are considered to be able to detect cardiac dysfunction at an earlier stage.

Each of the three cardiac imaging modalities has its strengths and limitations:

Transthoracic echocardiography (TTE) is widely used due to its availability, ease of use and absence of radiation. It has the advantage of evaluating not only systolic, but also diastolic and longitudinal function, valve and pericardial disease. However the poor test-retest reproducibility with 2D echocardiography (2DE) reported in previous studies raises concern about the accuracy of the technique, and the risk of erroneously stopping chemotherapy due to changes on LVEF that are only due to measurement noise. Indeed, some studies showed disappointing results, with 11% being the smallest change in EF that can be recognized with 95% confidence. Its limitation of relying on 2D geometrical assumptions in a single plane to estimate ventricular ejection is overcome by three dimensional echocardiography (3DE) which acquires more precise anatomic datasets and has been shown to be more accurate than 2DE for LVEF and volumes.

MUGA, is also a 3D technique that has consistently outperformed 2DE with respect to accuracy, reproducibility, intra and inter-observer variabilities for LVEF measures . It also has the advantage of few technical limitations (obesity, pacemakers and poor windows don´t affect image quality). However, radiation exposure is a common concern. 20-30 mCi of Tc99 exposes patients to 5-10 mSv of radiation, although the linkage of such low levels to increase cancer risk has not been shown.