Trends in leukemia-related mortality with heart failure as a contributing cause among U.S. adults aged ≥55 years, 1999–2023.

e24001 Background: Advances in leukemia therapy have improved survival, but cardiotoxic exposures and aging-related comorbidity may increase heart failure (HF) involvement in leukemia-related deaths. Trends in HF involvement are not well described. We examined national temporal trends in leukemia-related mortality involving HF among U.S. adults aged ≥55 years. Population-level HF trends can guide cardio-oncology risk mitigation and survivorship care. Methods: We used CDC WONDER Multiple Cause of Death data (1999–2023)—with bridged-race data through 2020 and single-race data for 2021–2023—to identify decedents aged ≥55 years with leukemia (ICD-10 C91–C95) as the underlying cause of death and heart failure (ICD-10 I50.x) listed as a contributing (multiple) cause. We calculated age-adjusted mortality rates (AAMR) per 100,000 population (2000 U.S. standard) overall and by sex and race/ethnicity, and age-specific crude mortality rates for adults aged ≥85 years. Temporal trends were modeled using weighted log-linear regression of ln(rate) by year, with standard errors derived from CDC WONDER 95% CIs to estimate annual percent change (APC) and 95% CIs. We report APCs to quantify rate-based change independent of population growth. Results: We identified 25,373 leukemia-related deaths with HF as a contributing cause among adults aged ≥55 years from 1999–2023 (14,311 male; 11,062 female). Overall AAMR was stable (1.6 per 100,000 in 1999 and 2023; APC 0.01%/year, 95% CI −0.74 to 0.76), while deaths increased from 946 (1999) to 1,459 (2023). Rising counts despite stable rates are consistent with population aging and growth. Male AAMR remained higher than female AAMR (2.2 to 2.3 vs 1.3 to 1.1), with no significant change over time (males: APC 0.48%/year, 95% CI −0.16 to 1.12; females: APC −0.41%/year, 95% CI −1.00 to 0.19). Rates were stable for NH White adults (1.7 to 1.8; APC 0.55%/year, 95% CI −0.17 to 1.28) and NH Black adults (1.1 to 1.0; APC 0.16%/year, 95% CI −0.77 to 1.10). Hispanic/Latino rates were low and stable in reliable years (0.8 in 2001 to 0.7 in 2023; APC 0.03%/year, 95% CI −1.28 to 1.36). Adults aged ≥85 years had higher age-specific crude mortality (8.1 to 7.8 per 100,000; APC 0.17%/year, 95% CI −0.45 to 0.79), with 484 deaths in 2023. Adults ≥85 accounted for a substantial share of HF-involved leukemia deaths, indicating concentrated risk. Conclusions: From 1999–2023, leukemia-related mortality with HF as a contributing cause was stable, despite rising death counts, with persistent differences by sex and race/ethnicity and a high burden among adults aged ≥85 years. These findings support integrating HF risk assessment, cardiotoxicity mitigation, and longitudinal HF monitoring into leukemia care and survivorship, particularly for older adults and other high-burden groups. Future work should evaluate treatment- and subtype-specific contributors to HF involvement.