Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 21 1 2026 04 26 50 70 Mohammadsadegh Talebi Kahdouei Fetal and Pediatric Cardiovascular Research Center, Children’s Medical Center, Tehran, Iran, Islamic Republic Of Hosein Ghasempour Fetal and Pediatric Cardiovascular Research Center, Children’s Medical Center, Tehran, Iran, Islamic Republic Of Fatemeh Aghaei Fetal and Pediatric Cardiovascular Research Center, Children’s Medical Center, Tehran, Iran, Islamic Republic Of Elaheh Vafaei Fetal and Pediatric Cardiovascular Research Center, Children’s Medical Center, Tehran, Iran, Islamic Republic Of Behnaz Sohrabi School of Medicine, Isfahan University of Medical Science, Isfahan, Iran, Islamic Republic of Ehsan Aghaei Moghadam Fetal and Pediatric Cardiovascular Research Center, Children’s Medical Center, Tehran, Iran, Islamic Republic Of Negin Rahimidanesh School of Medicine, Islamic Azad University, Tehran Medical Branch, Tehran, Iran, Islamic Republic of, Ali Dahmarde Ei Department of General Surgery, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran, Islamic Republic of Mojtaba Shurmij Department of General Surgery, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran, Islamic Republic of 2025 11 17 2026 01 11 Background: Rheumatic heart disease (RHD) remains a major cause of preventable cardiovascular morbidity and mortality, particularly in low- and middle-income countries. Despite the World Health Organization’s 2018 resolution calling for global elimination of RHD, substantial disparities in disease burden persist across regions and levels of socio-economic development. While previous studies have reported global trends, a clear comparative assessment of long-term changes in both fatal and non-fatal RHD burden across socio-demographic and geographic regions remains limited. This study aimed to assess long-term changes in the global burden of RHD between 1990 and 2021, with a specific focus on regional and socio-demographic disparities, using the most recent estimates from the Global Burden of Disease (GBD) 2021 study. We additionally assessed temporal trends across Socio-demographic Index (SDI) groups and GBD regions, with a specific focus on fatal (YLL) and non-fatal (YLD) components of disease burden. Methods: We conducted a secondary analysis of model-based estimates from the Global Burden of Disease (GBD) 2021 study to assess the burden of RHD between 1990 and 2021. Metrics included age-standardized and all-age incidence, prevalence, mortality, years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY). Data were stratified by five Socio-demographic Index (SDI) levels and 13 global regions. Estimates were produced using DisMod-MR 2.1 and CODEm and are reported as means with 95% uncertainty intervals (UIs). Results: Globally, age-standardized mortality and DALY rates for RHD declined by 56% and 53%, respectively, from 1990 to 2021. YLL decreased by 59%, while YLD rose by 11%, indicating a shift toward chronic non-fatal burden. For instance, the global age-standardized mortality rate fell from 9.1 (95% UI: 8.4–9.8) to 4.0 (3.6–4.5) per 100,000. High and high-middle SDI regions achieved the greatest reductions across all indicators. In contrast, low and low-middle-SDI regions experienced persistently high absolute deaths and DALYs, with South Asia alone accounting for over 27% of global RHD deaths in 2021. Females consistently bore a higher non-fatal burden (YLD) than males. Although the dataset includes the COVID-19 era, the specific impacts of the pandemic on RHD care and outcomes warrant further investigation. Across all SDI groups and regions, declines in DALYs were largely driven by reductions in years of life lost (YLLs), whereas years lived with disability (YLDs) remained relatively stable. Conclusions: While global RHD mortality has declined, substantial regional and socioeconomic disparities persist. The epidemiologic transition towards disability highlights the need for long-term care infrastructure, particularly for women, children, and low-SDI regions. While based on modelled estimates, this analysis offers the best available insight into global RHD epidemiology and informs data-driven health policy and planning. Despite overall improvements, substantial disparities persist between low and high SDI settings, underscoring the need for context-specific prevention and long-term management strategies. https://jthc.tums.ac.ir/index.php/jthc/article/view/2392 https://jthc.tums.ac.ir/index.php/jthc/article/download/2392/1255