Abstract Body (Do not enter title and authors here): Background
Myelodysplastic syndrome with ring sideroblasts (MDS-RS) is defined by macrocytic anemia, ineffective erythropoiesis, and ≥15% ring sideroblasts, often linked to SF3B1 mutations. Though lower-risk for leukemia, MDS-RS carries cardiovascular risk due to anemia-induced myocardial strain and transfusion-related iron overload.
Objective
To evaluate the cardiovascular impact of MDS-RS and the effects of ESAs, iron chelation, Luspatercept, and Imetelstat on hematologic and cardiac outcomes.
Methods
We conducted a PRISMA-guided review (2014–2024) using Scopus, PubMed, Embase, and ClinicalTrials.gov. Fourteen studies met criteria, including adults with MDS-RS or MDS/MPN-RS-T, reporting outcomes on transfusion burden, cardiac complications, or treatment efficacy (3 RCTs, 7 observational, 4 real-world/QoL).
Results
Luspatercept and Imetelstat led to ≥8-week transfusion independence in 37.9% and 40% of patients, respectively; Imetelstat also showed 42% hematologic improvement, particularly in those with shorter telomeres (Fenaux et al., 2020; Komrokji et al., 2024). Deferasirox-based iron chelation reduced myocardial iron burden, evidenced by a 36.8% increase in cardiac MRI T2* over two years. Among treated patients, 56.7% with moderate iron overload normalized T2*, and 42.9% with severe baseline iron improved to moderate range (Angelucci et al., 2020). ESAs modestly reduced transfusion need but had poor durability; 65% failed within 8 weeks, and nearly half relapsed (Makinde et al., 2023). ESA response declined in patients with high EPO or SF3B1 mutations, and thromboembolism was more frequent in older adults and MDS/MPN-RS-T cases (Antelo et al., 2020). Other studies linked transfusion burden to cardiac iron overload and ventricular dysfunction (Zhu et al., 2016; Buckstein et al., 2023; Herrera et al., 2020, 2024; Zeidan et al., 2022). Anemia-related myocardial strain was confirmed via echocardiography (Shenoy et al., 2014). Luspatercept improved fatigue, dyspnea, and quality of life in real-world studies (Mukherjee et al., 2022; Oliva et al., 2021; Komrokji et al., 2022).
Conclusion
MDS-RS imposes hematologic and cardiac burdens. While ESAs remain an early option, Luspatercept, Imetelstat, and iron chelators offer more durable hematologic and cardiac benefit. Biomarker-driven, cardio-hematologic care is essential to optimize outcomes.