Novel real-time 3-dimensional echocardiographic assessment of right and left ventricular function in anthracycline-treated survivors of childhood malignancies

Professor Cheung, Yiu Fai   (Principal Investigator (PI))

Professor Chan Godfrey Chi Fung   (Co-Investigator)

29

2008-01-01

61956

Novel real-time 3-dimensional echocardiographic assessment of right and left ventricular function in anthracycline-treated survivors of childhood malignancies

paediatric cancer survivors, three-dimensional echocardiography, ventricular function

Cardiovascular Research,Cancer

200707176073

Small Project Funding

2007

Completed

Anthracyclines are widely used for the treatment of solid tumours and haematological malignancies in children. While the introduction of anthracyclines has significantly improved the survival rates of childhood cancer, the long-term side effect of cardiotoxicity remains an issue of concern. The pathogenesis of cardiotoxicity is proposed to be related to free radical generation and disruption of myocyte calcium regulation. Damage and myocardial edema within both the left and right ventricles have been identified using magnetic resonance imaging. Importantly, no safe dose of anthracyclines free of cardiotoxicity has been found. Serial monitoring of cardiac function has therefore been advocated for early identification of myocardial damage and timely institution of medical therapy. Furthermore, limited data suggest potential usefulness of exercise echocardiography for unmasking latent cardiac dysfunction in anthracycline-treated survivors of childhood cancer. The most widely used imaging modality for the assessment of cardiac function and diagnosis of cardiotoxicity in these patients is two-dimensional echocardiography given its non-invasive nature. The function of the left ventricle, in particular, has been the focus of attention. The most commonly used echocardiographic parameters to assess left ventricular (LV) function in these patients are LV shortening fraction and LV ejection fraction, the latter calculated from 2-dimensional images based on geometric assumptions. Nonetheless, the major limitations of 2-dimensional echocardiography include the need to make assumptions of the LV geometry and a large inter-observer variability. Assessment of right ventricular (RV) function is even more difficult due to the complex geometry and asymmetry of the right ventricle. Not surprisingly, data on RV function in long-term survivors of childhood malignancies are extremely limited. In an attempt to overcome these limitations, alternative techniques for 3-dimensional reconstruction of the left and right ventricles using multiple echocardiographic planes have been developed, albeit time-consuming and prone to movement artifacts. Furthermore, geometric modeling to translate these multiplanar measurements into volumes is still required. Recently, real-time 3-dimensional (RT3D) or so-called 4-dimensional (4D) echocardiographic technology that allows fast acquisition of data sets encompassing the entire left ventricle and direct quantification of LV volumes and ejection fraction, but without the need for multiplane tracing or geometric modeling, has been introduced. Studies that compared the 2-dimensional and RT3D echocardiographically derived LV volumes in adult cardiac patients with those obtained from cardiac magnetic resonance have shown that RT3D echocardiography allows rapid (<2 minute/patients for data analysis), accurate (correlation coefficient: 0.96, 0.97, and 0.93 for end-diastolic volume, end-systolic volume, and ejection fraction, respectively) and reproducible measurement of LV volumes. Furthermore, RT3D-derived indices of LV volume and function have been validated against reference values obtained from radial long-axis cardiac magnetic resonance images. Apart from derivation of LV volume and function, RT3D echocardiographic technology in the determination of right ventricular (RV) volume and ejection fraction has also recently been validated using cardiac magnetic resonance. While cardiac magnetic resonance is currently considered the reference technique for measuring ventricular volumes and ejection fraction, it remains limited by cost and availability. Serial assessment of ventricular function with radionuclide ventriculography using multigated acquisition is similarly elaborate and expensive. Given the encouraging validation results in adult cardiac patients, we hypothesize that the novel RT3D echocardiographic imaging is useful for the assessment of LV and RV function in long-term survivors of childhood malignancies. To test this hypothesis, the following issues would be addressed in this study: i) feasibility and reproducibility of using RT3D echocardiography in assessing right and left ventricular volumes and systolic function, ii) effect of exercise stress on RT3D-derived right and left ventricular ejection fraction, as compared to age- and sex-matched control subjects, iii) significant determinants of LV and RV systolic function, and iv) relation of arterial dysfunction, demonstrated recently to occur in this patient cohort, on LV systolic function.