Hemoglobin Trajectories on SGLT2 Inhibitor Therapy in Heart Failure: Anemia Marks Adverse Prognosis While...

Background/Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) raise hemoglobin in patients with heart failure (HF). We characterized the prevalence, dynamics, predictors and prognostic implications of three hemoglobin states (anemia, normal, and erythrocytosis) at baseline and during the first year on SGLT2i therapy. Methods: Prospective single-center registry of 1244 HF patients with a baseline hemoglobin who initiated dapagliflozin or empagliflozin (March 2022-October 2025). Hemoglobin was categorized at baseline, 6 and 12 months using WHO sex-specific thresholds. We analyzed inter-category transitions, predictors of each hemoglobin category at each timepoint, time-to-event outcomes (all-cause death, MACE, thrombosis) in landmark analyses, and the correlation of hemoglobin change with concurrent changes in left ventricular ejection fraction and NT-proBNP. Results: At baseline, 23.6% had anemia, 71.1% were normal, and 5.3% had erythrocytosis. The prevalence of erythrocytosis remained low throughout, with a modest, transient rise to 8.0% at 6 months before returning toward baseline (5.9% at 12 months), even though the underlying composition of patients was highly dynamic. Among baseline-normal patients, downward transition to anemia (7.8% at 6 months, 9.2% at 12 months) occurred at rates equal to or greater than upward transition to erythrocytosis (7.7% and 6.0%, respectively). The prevalence of anemia decreased significantly between baseline and the follow-up timepoints. Across timepoints, the patient's own baseline hemoglobin was the dominant independent predictor of both subsequent erythrocytosis and subsequent anemia. Other independent predictors of erythrocytosis were higher adherence to SGLT2i, male sex, current smoking, COPD or asthma, higher heart rate and lower serum albumin. Other independent predictors of anemia were non-adherence to or discontinuation of SGLT2i, peripheral arterial disease, advanced age, diabetes, lower eGFR, higher NT-proBNP and lower serum albumin. Increases in hemoglobin from baseline were associated with greater concurrent reductions in NT-proBNP at 6 and 12 months but were not associated with changes in LVEF at either timepoint. Anemia was independently associated with all-cause death at the baseline and 6-month landmarks (adjusted HRs are 2.23 and 2.45, respectively; time-varying HR is 2.55), with a consistent but non-significant point estimate at 12 months (aHR of 1.90), and with significant 6-month MACE estimate (aHR of 3.07). Erythrocytosis was not associated with mortality, MACE or thrombosis at any timepoint, although the small number of patients and thrombotic events limits interpretation. Dapagliflozin and empagliflozin were associated with indistinguishable hemoglobin trajectories. Conclusions: On SGLT2i therapy, anemia carries the dominant prognostic signal and identifies a high-risk subgroup; erythrocytosis is uncommon, transient and showed no detectable association with adverse outcomes, though thrombotic events were too few for firm safety conclusions. Routine monitoring of hemoglobin for anemia is of higher clinical importance compared to erythrocytosis; these single-center findings require external validation.