Authors

• Tomislav Čikara — University Hospital Dubrava, Zagreb, Croatia — ORCID: 0000-0001-8012-4481
• Marko Lucijanić — University Hospital Dubrava, Zagreb, Croatia — ORCID: 0000-0003-3962-2774
• Marin Pavlov — University Hospital Dubrava, Zagreb, Croatia — ORCID: 0000-0003-3962-2774
• Irzal Hadžibegović — University Hospital Dubrava, Zagreb, Croatia — ORCID: 0000-0002-3768-9134
• Nikola Pavlović — University Hospital Dubrava, Zagreb, Croatia — ORCID: 0000-0001-9187-7681
• Šime Manola — University Hospital Dubrava, Zagreb, Croatia — ORCID: 0000-0001-6444-2674
• Ivana Jurin — University Hospital Dubrava, Zagreb, Croatia — ORCID: 0000-0002-2637-9691

Keywords

SGLT-2 inhibitors, polycythemia vera, heart failure

DOI

Full Text

**Introduction**: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are the latest addition to guideline-directed medical therapy in heart failure (HF) (1). It has been documented that SGLT-2 inhibitors significantly increase hemoglobin (Hgb) and hematocrit (Hct) levels via several supposed mechanisms (2). We analyzed SGLT-2 inhibitors treated HF patients and dynamics of Hgb and Hct levels in follow-up period of 12 months. **Metods**: We consider all of patients with or developing Hgb levels >160 g/L for females or >165 g/L for males to represent secondary polycythemia (SP). **Patients and Results**: We analyzed a total of 848 SGLT-2 inhibitor treated HF patients. At the baseline, median Hgb was 136 g/L, IQR (124-147). A total of 31 (3.7%) patients fulfilled WHO criteria for polycythemia. At 6 months, median Hgb was 140 g/L, IQR (127-150) and was significantly higher in comparison to baseline (P0.05 for both analyses). However, structure of the patient cohort presenting with SP significantly differed over time (P<0.001) as shown in **Figure 1**. About 1% of patients had persistent SP at both 6 months in comparison to baseline and at 12 months in comparison to baseline and 6 months milestone. However, during first 6 months 4% of patients developed de-novo SP in comparison to baseline, whereas 2% of patients experienced SP resolution. At subsequent 6 months, 3% of new patients developed SP and 3% of new patients experienced SP resolution in comparison to first 6 months period. Overall, during 12 months similar proportion of patients developed SP and experienced SP resolution, whereas 1% of patients had persisting SP. FIGURE 1. Dynamics of secondary polycythemia in a heart failure patients over 6 and 12 months of follow-up. SP = secondary polycythemia **Conclusion**: These observations shed novel light on phenomenon of erythrocytosis developing in association with SGLT-2 inhibitor use in HF patients. As our data show, there is continuous exchange of patients who develop and resolute SP over time with only a fraction of them (1%) experiencing persistent polycythemia, and therefore probably require further hematologic workup.

Literature

1. Talha KM, Anker SD, Butler J. SGLT-2 Inhibitors in Heart Failure: A Review of Current Evidence. Int J Heart Fail. 2023 March 13;5(2):82–90. https://doi.org/10.36628/ijhf.2022.0030
2. Gangat N, Szuber N, Alkhateeb H, Al-Kali A, Pardanani A, Tefferi A. JAK2 wild-type erythrocytosis associated with sodium-glucose cotransporter 2 inhibitor therapy. Blood. 2021 December 30;138(26):2886–9. https://doi.org/10.1182/blood.2021013996