Session: 114. Hemoglobinopathies, Excluding Thalassemia—Clinical: Assessment and Prevention of End-Organ Injury in Sickle Cell Disease
Hematology Disease Topics & Pathways:
The median age of the 630 adult SCD patients was 37 years. 47% were male, 77% had the HbSS phenotype, and 22 (3.7% of 592 with follow-up data) died during a median time of follow up of 29 months. The most frequent changes in vital signs identified were increases in the heart rate (90%) followed by increases in systolic blood pressure (77%, Table 1b). Bivariate analysis revealed significant but weak positive correlations between tricuspid regurgitation velocity (TRV) and increases in both heart rate (r= 0.08; p<0.05) and systolic blood pressure (r=0.13; p=0.002), as well as decreases in O2 saturation (r=-0.09; p=0.03). Significant positive correlations were also identified between increases in pulse pressure and TRV (r=0.14; p=0.001), left ventricular mass index (r=0.10, p=0.02), and a composite index of hemolysis (r=0.09; p =0.03). Pulse pressure increased more during 6MWT in patients with self-reported pulmonary hypertension than patients without pulmonary hypertension (median 1.6 vs. 1.3 per 100-meter walk, p=0.04); while heart rate increased less (median 3.4 vs. 4.3 per 100-meter walk, p=0.04). LASSO models selected TRV and markers of hemolysis as predictors of O2 desaturation, while higher left ventricular ejection fraction and non-SS genotypes were predictors of lesser O2 desaturation, during the 6MWT. Both older age and higher left ventricular volume were associated with reduction of diastolic blood pressure during 6MWT (Table 1a). In survival analysis, after adjusting for TRV and N-terminal pro-brain natriuretic peptide concentration, any increase in systolic blood pressure during the 6MWT was associated with better survival (hazard ratio=0.3, p=0.019, Table 1b).
These findings support links between changes of vital signs during the 6MWT and established markers of hemolysis and cardiovascular dysfunction in SCD patients. Evidence of a protective effect of increased systolic pressure is a novel finding. This might indicate that the ability to increase systolic pressure during submaximal exercise relates to cardiac output and conveys a physiological advantage for SCD patients. These findings could be used as the basis for future mechanistic studies of exercise effects on cardiovascular function in SCD patients.
Disclosures: Gordeuk: Imara: Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Novartis: Consultancy; CSL Behring: Consultancy, Research Funding; Ironwood: Research Funding. Gibbs: Pfizer: Consultancy; United Therapeutics: Consultancy; MSD: Consultancy; GSK: Consultancy; Complexa: Consultancy; Bayer: Consultancy; Actelion: Consultancy; Acceleron: Consultancy. Little: BioChip Labs: Patents & Royalties: SCD Biochip (patent, no royalties); GBT: Membership on an entity's Board of Directors or advisory committees; NHLBI: Research Funding; Hemex Health, Inc.: Patents & Royalties: Microfluidic electropheresis (patent, no royalties); Bluebird Bio: Research Funding; GBT: Research Funding. Gladwin: Globin Solutions: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Not relevant to SCD; Bayer: Consultancy, Research Funding; Actelion: Consultancy; Pfizer: Consultancy; Novartis: Consultancy.
See more of: Oral and Poster Abstracts