The six-minute walk test (6MWT) has been used in patients with sickle cell disease (SCD), in conjunction with tricuspid regurgitant velocity (TRV) and plasma N-terminal pro-brain natriuretic peptide (NT-pro BNP), to assess risk of having pulmonary hypertension. Exercise-induced vital sign changes (VSCs) are predictors of clinical outcomes in other diseases. In this study, we assess the predictors and prognostic value of 6MWT VSC in adult SCD patients. Data from a multinational study of SCD patients (Treatment of Pulmonary Hypertension with Sildenafil: walk-PHaSST) were used to calculate the 6MWT VSC. Predictors of VSC were identified by a multivariable analysis, and a survival analysis was conducted by the Cox proportional hazard method. An increase in heart rate was observed in 90% of the 630 SCD adults, 77% of patients had an increase in systolic blood pressure (SBP), and 50% of patients had a decrease in oxygen saturation. TRV (odds ratio [OR] = 1.82, p = .020), absolute reticulocyte count (OR = 1.03, p < .001), and hemoglobin (OR = 0.99, p = .035) predicted oxygen desaturation ≥ 3% during the 6MWT. In the adjusted analysis, SBP increase during the 6MWT was associated with improved survival (hazards ratio = 0.3, 95% confidence interval: 0.1-0.8). Increases in heart rate and blood pressure, as well as oxygen desaturation, are common in adults with SCD during the 6MWT. VSC is associated with markers of anemia and TRV and can be used for risk stratification. Any increase in SBP during the 6MWT was associated with improved survival and may be indicative of a patient's ability to increase stroke volume.
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