Abstract
Background: Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders that predominantly affect older adults and are characterized by ineffective hematopoiesis, progressive cytopenias, and a heightened risk for progression to acute myeloid leukemia. Cardiovascular complications, particularly heart failure (HF), are increasingly recognized as major contributors to morbidity and mortality in patients with MDS, yet national level data on long-term HF mortality trends in this population remain scarce. Understanding temporal and demographic patterns of HF-related deaths in MDS patients is crucial for risk stratification and developing preventive strategies.
Methods: We conducted a retrospective population-based analysis using the CDC WONDER Multiple Cause of Death database to examine HF-related mortality among individuals with MDS between 1999 and 2023. Age-adjusted mortality rates (AAMRs) were calculated per million using U.S. Census data as the denominator. Temporal trends were assessed using Joinpoint regression to determine average annual percent changes (AAPCs). ARIMA models with Box-Cox transformation were fitted after ADF/KPSS tests, with validation by residual checks to forecast future trends from 2024–2030. Subgroup analyses were stratified by sex, race, ethnicity, region, and urbanization level.
Results: Between 1999 and 2023, there were 4,947 HF related deaths among individuals with MDS in the United States. Over this period, the AAMR rose from 2.5 per million in 1999 to 2.7 per million in 2023, with notable upward inflections going upto 3 per million in 2007, 2009, 2021 and 2022, however coming back down to 2.7 per million in 2023. Gender-specific trends showed a higher burden in males, whose AAMR increased from 3.9 to 4.1 per million (5% increase), compared to females whose AAMR declined from 1.8 to 1.7 per million (5% decrease).
Racial disparities persisted throughout the study period. White individuals accounted for the majority of deaths, with AAMR increasing from 2.7 to 3 per million. Black individuals experienced a more rapid rise, from 1.1 in 1999 to 1.5 in 2023, a 36% increase. Hispanic or Latino individuals saw an increase from 1.2 to 1.3 per million, while non-Hispanic individuals rose from 2.5 to 2.8 per million. Both peaked around 2019-2022 and declined again in 2023.
Geographically, the Northeast and Midwest carried the highest burden, peaking at 4.4 and 4.2 per million, respectively, while the South and West exhibited lower yet steadily increasing trends. By 2023, AAMR reached 4.0 in the South and 3.7 in the West. Urbanization analysis revealed the highest AAMRs in small metro (4.3) and micropolitan areas (4.1), while large central metro areas consistently had lower burdens (3.6 in 2023).
Based on ARIMA modeling, the AAMR for HF-related mortality in MDS is projected to continue rising steadily. Forecasted rates include 2.64 in 2024, 2.68 in 2026, 2.69 in 2028, and 2.70 per million by 2030 (95% CI: 2.42–3.03), suggesting a persistent but decelerating growth pattern.Conclusion: HF-related mortality among MDS patients in the U.S. has risen markedly over the past two decades, with persistent disparities by sex, race, and geography. Forecasts indicate a continued, albeit plateauing, burden through 2030. These findings suggest the need for targeted cardiovascular risk mitigation strategies in MDS care, particularly in high-risk subgroups.
