1. Comparison of Echocardiographic Methods to Cardiac Magnetic Resonance Imaging in Survivors of Pediatric Cancer Jeet Mehta 1, Sanket Shah 1,2 Wendy McClellan 2, Joy M. Fulbright 2, Jignesh D. Dalal 1,2, Joshua Q. Knowlton 1,2, Ashley K. Sherman 2, Anitha Parthiban 1,2, Girish Shirali 1,2 1 UMKC School of Medicine, 2 Children’s Mercy Hospital Introduction Pediatric echocardiogram labs report left ventricle [LV] ejection fraction [EF] using either M-mode [MM] or 2D echo [2DE] for cancer patients. In adults, 3D echo [3DE] measurement of LV volume and function is now rapid, more accurate and reproducible than 2DE and MM. Our study aims to show the feasibility and validity of 3DE measurements in pediatric cancer patients in comparison to cardiac MRI as gold standard, and to compare with other methods, including MM and 2DE. Methods The study population consisted of children and young adults being followed up after cancer remission at Children’s Mercy Hospital. Families with children older than 10 years of age who have survived > 2 years after completion of cancer treatment were enrolled to participate in the study. An MRI was performed the same day as clinically- indicated echocardiograms wherein LV function was quantified using MM and 2DE. Additional 3DE images were acquired from the apical window. MM, 2DE and 3DE ventricular volume and function analysis was performed offline using programs such as Xcelera and QLab (Philips) and blinded to MRI measurements. The study is approved by the institutional review board [IRB] of Children’s Mercy Hospital. Results For the 41 subjects studied, age ranged from 10 to 22 years, with a median duration of cancer remission of 10 years. Forty had received anthracyclines [median dose of 175 mg/m 2 of body surface area and 9 subjects receiving dosage of ≥300 mg/m 2 ], 32 had received alkylating agents, 20 had radiation therapy; 20 were girls and 39 were Caucasians. Satisfactory 3DE images were obtained in 37/41 subjects; MRI was obtained in all 41. LV end-diastolic volume by 3DE had a stronger correlation with MRI (gold standard) [r=0.71, p<0.01] as compared to 2DE [r=0.59, p<0.01] and MM [r=0.64, p<0.01]. Six subjects had mild LV dysfunction [defined as] Cardiac Magnetic Resonance LV EF of <55%; none had EF <50%. 3DE had higher sensitivity [40%], specificity [100%], positive predictive value [100%] and negative predictive value [91%] for detecting LV dysfunction when compared with MM and 2DE (See Table below). No subjects had notable valvular dysfunction and all subjects were asymptomatic from a cardiovascular standpoint [New York Heart Association class I]. Summary We performed extensive cardiac imaging of 41 pediatric cancer survivors using various methods. Left ventricular ejection fraction <55 % is widely considered as abnormal systolic function and it has been validated in multiple outcome studies to correlate with higher cardiovascular morbidity and mortality. With a median duration of remission of 10 years, there were 6 subjects with mild LV dysfunction [defined as] CMR LV EF of <55% but none had EF <50% and none had cardiovascular symptoms. It is possible that their cardiac function may decline and they may become symptomatic. However, it appears at this point, that the careful dose selection by the oncologists has reduced the prevalence of symptomatic or overt heart failure. 2D Echocardiography remains the mainstay of cardiac function evaluation, but now, 3D echocardiography is widely available from all manufacturers of echocardiography machines. The table on left shows the sensitivity, specificity, and predictive values of the various echocardiography methods. When compared to cardiac MRI as gold standard, 3D echocardiography was very specific in identifying those with MRI LV EF of <55%. Also, M-mode and 2D echocardiography had an additive effect in accurately identifying those with MRI LV EF of <55%. Conclusion 3DE measurement of LV volumetrics is feasible and correlates better with MRI than do MM and 2DE. This modality should be considered for routine usage in pediatric cancer patients following completion of therapy. Figure 2. 2D Echocardiogram (Apical chamber view) Figure 3. 3D Echo (4ch and 2ch view; arrow at LV volume measurement) Figure 4. Cardiac MRI (Short axis SSFP image) References 1.Steinherz LJ, et al. Cardiac toxicity 4 to 20 years after completing anthracycline therapy. JAMA. 1991;266:1672-7. 2.Alvarez JA, et al. Long-term effects of treatments for childhood cancers. Curr Opin Pediatr. 2007;19:23-31. 3.Oeffinger KC, et al. Chronic health conditions in adult survivors of childhood cancer. N Engl J Med. 2006;355:1572-82. 4.Nousiainen T, et al. Early decline in left ventricular ejection fraction predicts doxorubicin cardiotoxicity in lymphoma patients. Br J Cancer. 2002;86:1697-1700. 5.Kronik G, et al. Comparative value of eight M-mode echocardiographic formulas for determining left ventricular stroke volume. Circulation. 1979;60(6):1308-16. 6.Feigenbaum H AW, Ryan T, ed Feigenbaum’s echocardiography. Philadelphia: Lippincott Williams & Wilkins; 2005. Feigenbaum H AW, Ryan T, ed. Evaluation of systolic and diastolic function of the left ventricle. 7.Lopez L, et al. Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr. 2010;23:465-95 8.Lipshultz SE, et al. Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. N Engl J Med. 1991;324:808-15. Figure 1. M-mode image parasternal short axis of the heart Echocardiogram Method Sensitivity %Specificity % % Positive predictive vale % Negative predictive value MM 17975087 2DE 17892086 3DE 40100 91 All combined 5087.542.990.3