Gregory T Armstrong1, Vijaya M Joshi2, Kirsten K Ness3, Thomas H Marwick4, Nan Zhang5, DeoKumar Srivastava5, Brian P Griffin6, Richard A Grimm6, James Thomas7, Dermot Phelan6, Patrick Collier6, Kevin R Krull3, Daniel A Mulrooney8, Daniel M Green3, Melissa M Hudson8, Leslie L Robison3, Juan Carlos Plana9. 1. Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee. Electronic address: greg.armstrong@stjude.org. 2. Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee. 3. Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee. 4. Menzies Research Institute, University of Tasmania, Hobart, Australia. 5. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee. 6. Department of Cardiovascular Medicine, The Cleveland Clinic, Cleveland, Ohio. 7. Bluhm Cardiovascular Institute, Northwestern Memorial Hospital, Chicago, Illinois. 8. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. 9. Baylor College of Medicine, Houston, Texas.
Abstract
BACKGROUND: Treatment-related cardiac death is the primary, noncancer cause of mortality in adult survivors of childhood malignancies. Early detection of cardiac dysfunction may identify a high-risk subset of survivors for early intervention. OBJECTIVES: This study sought to determine the prevalence of cardiac dysfunction in adult survivors of childhood malignancies. METHODS: Echocardiographic assessment included 3-dimensional (3D) left ventricular ejection fraction (LVEF), global longitudinal and circumferential myocardial strain, and diastolic function, graded per American Society of Echocardiography guidelines in 1,820 adult (median age 31 years; range: 18 to 65 years) survivors of childhood cancer (median time from diagnosis 23 years; range: 10 to 48 years) exposed to anthracycline chemotherapy (n = 1,050), chest-directed radiotherapy (n = 306), or both (n = 464). RESULTS: Only 5.8% of survivors had abnormal 3D LVEFs (<50%). However, 32.1% of survivors with normal 3D LVEFs had evidence of cardiac dysfunction by global longitudinal strain (28%), American Society of Echocardiography-graded diastolic assessment (8.7%), or both. Abnormal global longitudinal strain was associated with chest-directed radiotherapy at 1 to 19.9 Gy (rate ratio [RR]: 1.38; 95% confidence interval [CI]: 1.14 to 1.66), 20 to 29.9 Gy (RR: 1.65; 95% CI: 1.31 to 2.08), and >30 Gy (RR: 2.39; 95% CI: 1.79 to 3.18) and anthracycline dose > 300 mg/m(2) (RR: 1.72; 95% CI: 1.31 to 2.26). Survivors with metabolic syndrome were twice as likely to have abnormal global longitudinal strain (RR: 1.94; 95% CI: 1.66 to 2.28) and abnormal diastolic function (RR: 1.68; 95% CI: 1.39 to 2.03) but not abnormal 3D LVEFs (RR: 1.07; 95% CI: 0.74 to 1.53). CONCLUSIONS: Abnormal global longitudinal strain and diastolic function are more prevalent than reduced 3D LVEF and are associated with treatment exposure. They may identify a subset of survivors at higher risk for poor clinical cardiac outcomes who may benefit from early medical intervention.
BACKGROUND: Treatment-related cardiac death is the primary, noncancer cause of mortality in adult survivors of childhood malignancies. Early detection of cardiac dysfunction may identify a high-risk subset of survivors for early intervention. OBJECTIVES: This study sought to determine the prevalence of cardiac dysfunction in adult survivors of childhood malignancies. METHODS: Echocardiographic assessment included 3-dimensional (3D) left ventricular ejection fraction (LVEF), global longitudinal and circumferential myocardial strain, and diastolic function, graded per American Society of Echocardiography guidelines in 1,820 adult (median age 31 years; range: 18 to 65 years) survivors of childhood cancer (median time from diagnosis 23 years; range: 10 to 48 years) exposed to anthracycline chemotherapy (n = 1,050), chest-directed radiotherapy (n = 306), or both (n = 464). RESULTS: Only 5.8% of survivors had abnormal 3D LVEFs (<50%). However, 32.1% of survivors with normal 3D LVEFs had evidence of cardiac dysfunction by global longitudinal strain (28%), American Society of Echocardiography-graded diastolic assessment (8.7%), or both. Abnormal global longitudinal strain was associated with chest-directed radiotherapy at 1 to 19.9 Gy (rate ratio [RR]: 1.38; 95% confidence interval [CI]: 1.14 to 1.66), 20 to 29.9 Gy (RR: 1.65; 95% CI: 1.31 to 2.08), and >30 Gy (RR: 2.39; 95% CI: 1.79 to 3.18) and anthracycline dose > 300 mg/m(2) (RR: 1.72; 95% CI: 1.31 to 2.26). Survivors with metabolic syndrome were twice as likely to have abnormal global longitudinal strain (RR: 1.94; 95% CI: 1.66 to 2.28) and abnormal diastolic function (RR: 1.68; 95% CI: 1.39 to 2.03) but not abnormal 3D LVEFs (RR: 1.07; 95% CI: 0.74 to 1.53). CONCLUSIONS: Abnormal global longitudinal strain and diastolic function are more prevalent than reduced 3D LVEF and are associated with treatment exposure. They may identify a subset of survivors at higher risk for poor clinical cardiac outcomes who may benefit from early medical intervention.
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