Survivors of Pediatric Hematopoietic Stem Cell Transplantation Exhibit Progressive Diastolic Dysfunction Over Years of Follow-Up.

Patients who have undergone hematopoietic stem cell transplantation (HSCT) in childhood have a higher risk of diastolic heart failure (HF). The rate of progression of diastolic dysfunction in aging pediatric patients is unknown and is more difficult to assess in young patients secondary to changes in diastolic indices as they grow. HSCT recipients at our center were previously found to have decline in diastolic function indices at 1 year after HSCT. This study provides follow-up of this cohort, using age-normalized z-scores to assess whether the decline in diastolic function noted at 1-year post-HSCT persists, worsens, or improves over time. Patients age <21 years who underwent HSCT at Boston Children's Hospital/Dana-Farber Cancer Center between 2005 and 2008 with ≥3 surveillance echocardiograms, including 1 performed pre-HSCT, were included. Diastolic measures included mitral inflow (E/A ratio) and Doppler tissue imaging of left ventricular lateral wall (LV lateral e'), LV septal wall (septal e') and right ventricular free wall (RV e'). Systolic function was measured by LV ejection fraction (LVEF). Normalization by age was done using z-scores, and >±2 SD was defined as abnormal in linear modeling of diastolic dysfunction and systolic dysfunction over time. In a subset of patients with adequate post-HSCT images of the entire left atrium (LA), LA volume and LA strain analyses also were performed. The study cohort comprised 61 patients (41% female; median age at HSCT, 10.7 years; median follow-up, 7.4 years). Diastolic index z-scores declined by -.045/year for LV lateral e', -.06/year for LV septal e', and -.14/year for RV e' (P < .01). The E/A ratio z-score increased by .034/year (P = .028). Linear modeling demonstrated that LV lateral e' and LV septal e' would become abnormal at 25 and 20 years post-HSCT, respectively, whereas RV e' would become abnormal sooner, at 12.6 years. LVEF z-score declined by -.04/year (P < .01) and was estimated to become abnormal at 40 years post-HSCT. Exposure to total body irradiation (TBI) was associated with worsening diastolic indices, lower LVEF (P ≤ .002), and decreased LA reservoir strain (42.0% versus 45.0%; P = .016) and conduit strain (-31.5% versus -35.1%; P = .029), although there was significant overlap between TBI and anthracycline exposure. Treatment with anthracyclines even at low doses (median, 150 mg/m

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