Abstract 13198: Immunohematologic Failure Identifies Fibrotic Phenotype in Heart Failure With Preserved Ejection Fraction

Abstract

Background: We have shown that immunohematologic failure (IHF: lymphopenia (absolute lymphocyte count (ALC)<1.5 x10 3 /μL) and anisocytosis (red cell distribution width, RDW > 14.5%)) is associated with risk of heart failure. Lymphopenic patients have elevated numbers of regulatory T cells with profibrotic phenotype. Hypothesis: We hypothesized that IHF is associated with fibrosis in HFpEF. Methods: We investigated the association between ALC, RDW, and IHF with markers of fibrosis (galectin-3 and Corboxy-Terminal Telopeptide of Collagen Type I [CITP]) in patients enrolled in RELAX trial of HFpEF (Clinicaltrials.gov NCT00763867) using linear regression, and adjusting for age, sex, race, eGFR, BMI and diabetes status. Results: A total of 122 patients with both ALC and RDW were included. There was a modest correlation between ALC and RDW (Spearman’s rho=-0.22, P=0.017). Both ALC and RDW were significantly associated with galectin 3 and CITP (figure). A total of 33 (27%) patients had IHF. Patients with IHF had lower GFR (62±25 vs 53 ± 21 ml/min/1.73 m 2 , P<0.001), lower peak VO2 (12.5±2.8 vs 11.0 ± 3.0 ml/kg/min, P=0.007), lower exercise capacity (78 ± 26 vs 64 ± 35 watts, P=0.018), higher NT-proBNP (900±1152 vs 1615 ± 1247 pg/mL, P=0.004), galectin-3 (13.3 ± 4.1 vs 17.7 ± 5.8, P<0.001 ng/mL) and CITP (6.1 ± 3.5 vs 11.0 ± 5.7 μg/L, P<0.001) but no difference in age, sex, race, CRP or diabetes status. After multiple adjustments, IHF was associated with higher galectin-3 levels (P=0.01) and CITP (P<0.001). Conclusions: Immunohematologic failure is common in HFpEF and is associated with fibrotic phenotype. The mechanisms linking IHF and fibrosis need to be elucidated in future studies.