Reduction of the Six-Minute Walk Distance in Children with Sickle Cell Disease Is Correlated with Silent Infarct: Results from a Cross-Sectional Evaluation in a Single Center in Belgium

BACKGROUND The 6-minute walk test (6 MWT) is used in adults and children affected by a wide range of chronic diseases to evaluate their sub-maximal exercise capacity. It reflects the global response of various physiological systems in a situation simulating a daily life activity. METHODS We analyzed factors affecting the 6 MWT in 46 Sickle Cell Disease children. Forty-two were treated with hydroxyurea (HU). Patients with normal test (>80% of the age-standardized predicted value) were compared to patients with abnormal test (≤ 80%). Baseline hematological values, clinical events, cerebrovascular disease, cardio-pulmonary parameters and disease-modifying treatment were compared according to the performance of the test. RESULTS Among the 46 patients, 14 had an abnormal 6 MWT. In univariate analysis, both groups were similar for biological and clinical data. Six of the 14 patients with an abnormal 6 MWT had silent infarct (SI) compared to 6/32 with a normal test (P = 0.09). When excluding chronically transfused patients, 4 of the 11 patients with an abnormal 6 MWT had SI compared to 1/26 (P = 0.02). Baseline pulse oximetry was normal in both groups but slightly lower in patients with abnormal 6 MWT (P = 0.02). No patient presented exercise-induced desaturation. In multivariate analysis, the only factor associated with abnormal 6 MWT was the presence of SI (P = 0.045). CONCLUSIONS In our cohort of 46 patients characterized by high exposure rate to HU and by the absence of severe cardiopulmonary disease, the sole factor independently associated with 6 MWT was the presence of SI. The lower exercise capacity of children with SI may reflect some subclinical neurological impairment as they do not differ by hemoglobin level or cardiopulmonary parameters.