Prognostic Value of Reticulocyte Production Ability in Patients With Chronic Heart Failure

Anemia is frequently observed and associated with mortality in patients with heart failure (HF). Although the quality of erythropoiesis is an intrinsic aspect of anemia's pathophysiology, its prognostic value in HF patients is unclear.

Between January 2020 and October 2023, 1328 symptomatic patients with chronic HF from a multicentre registry were prospectively examined. The reticulocyte production ability was evaluated by calculating the reticulocyte production index (RPI) using reticulocyte counts and serum hematocrit level. Patients were divided into 4 groups on the basis of the presence or absence of anemia and the median RPI. The primary outcome was a composite of all-cause death and hospitalization for worsening HF.

During a median follow-up of 551 (interquartile range, 321-712) days, the primary outcome occurred in 219 patients. The incidence of the primary outcome was high among patients in the anemia and higher RPI group (≥ 0.978) (P < 0.001). Higher RPI was independently associated with a higher risk of the primary outcome, even after adjusting for prognostic covariates (adjusted hazard ratio, 1.37; 95% confidence interval, 1.05-1.78). Erythrocyte counts were significantly higher in patients with higher RPI in the groups without anemia (P < 0.001); however, no significant differences were observed between the groups with anemia (P = 0.923). Serum iron levels and transferrin saturation did not significantly differ between the RPI groups with or without anemia.

Higher RPI, which might reflect impaired maturation or a shortened lifespan of erythrocytes, was associated with worse clinical outcomes in HF patients irrespective of iron status.