This is a Research Topic initiated by ISACB, the International Society for Applied Cardiovascular Biology.

Despite significant advances in global health, Rheumatic Heart Disease (RHD) has long suffered from underfunding and insufficient scientific attention, resulting in persistent gaps in both mechanistic understanding and therapeutic options. RHD remains a leading cause of cardiovascular morbidity and premature death, particularly among children and young adults in low- and middle-income countries and disadvantaged populations in otherwise affluent countries, with a disproportionate impact on women.

RHD results from an aberrant autoimmune response to repeated Streptococcus pyogenes (GAS) infections, progressing through acute rheumatic fever (ARF) and culminating in chronic valvular injury, particularly affecting the mitral valve. Recent advances in immunology, pathobiology, and omics technologies, have begun to illuminate the complex interplay between bacterial infection, inflammation, fibrosis, sex-specific immune responses, genetic susceptibility and environmental determinants. These findings offer new opportunities for targeted diagnostics, therapeutic innovation, and preventive strategies, including vaccines.

This Research Topic seeks high-quality contributions that explore the evolving landscape of RHD research, with a particular focus on global disease trends and emerging biological mechanisms.

We welcome submissions addressing, but not limited to:

• Global epidemiology and public health challenges of ARF and RHD

• Immunopathogenesis of rheumatic valve injury, including molecular mimicry, autoimmunity and the inflammatory cascade

• Sex-specific differences in RHD progression, immune response and outcome

• Pathology and cellular mechanisms such as Fibrosis, calcification, neoangiogenesis and lymphangiogenesis in rheumatic valve tissue

• Insights into transcriptomics, proteomics, and spatial biology

• Novel diagnostic tools, biomarker discovery and molecular diagnostics

• Insights into the echocardiographic assessment of ARF and RHD

• Preclinical models of ARF and RHD

• Advances in surgical, catheter-based, and medical therapies

• Effect of penicillin prophylaxis and alternatives

• Vaccine development and immune-protective responses to GAS

• Perspectives on implementation of health policy, and advocacy for at risk-populations

Article types accepted:

Original Research, Reviews, Mini Reviews, Methods, Perspectives, Editorials, Brief Research Reports, and Opinions.

This Topic offers a platform to elevate RHD as a global health priority while advancing mechanistic discovery and translational progress. We look forward to your contributions that will help redefine the scientific and clinical future of this preventable, yet devastating, disease.

Are you interested in contributing a manuscript to this Research Topic?

Rheumatic Heart Disease: Global Trends and Emerging Mechanisms