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Rheumatic Heart Disease: Inflammation, Immune Pathways, Valve Remodeling, and the Promise of SGLT2 Inhibitors
Trung Anh Mai1, Benjamin Marchandot2, Sandy Hmadeh3
1Department of Cardiology, University Hospital of Strasbourg, Strasbourg, France; UR3074 - Translational Cardiovascular Medicine, University of Strasbourg, Strasbourg, France; Groupe pour l'Enseignement et la Recherche Cardiologique en Alsace, Strasbourg, France; Vietnam National Heart Institute, Bach Mai Hospital, Hanoi, Vietnam; Rwanda Rheumatic Heart Disease Research Network, Kigali, Rwanda.
JACC. Basic to Translational Science
|July 16, 2026
Summary
Sodium-glucose cotransporter-2 (SGLT2) inhibitors show potential for treating rheumatic heart disease (RHD). Further research is needed to confirm their effectiveness in modifying RHD valvular disease progression.
Area of Science:
- Cardiology
- Pharmacology
- Rheumatology
Background:
- Rheumatic heart disease (RHD) is a major cause of acquired valvular heart disease in low- and middle-income countries, impacting millions.
- Currently, no effective pharmacological interventions exist to slow the progression of valvular disease in established RHD.
Purpose of the Study:
- To review the molecular and cellular pathology of RHD.
- To evaluate the potential of sodium-glucose cotransporter-2 (SGLT2) inhibitors in treating RHD based on their known cardioprotective mechanisms.
Main Methods:
- Synthesized current evidence on RHD pathology.
- Evaluated mechanistic plausibility of SGLT2 inhibitors in the context of RHD.
- Drew parallels from studies on non-rheumatic valve disease and experimental models.
Main Results:
- SGLT2 inhibitors may reduce oxidative stress, inflammation, fibrosis, and mitochondrial dysfunction implicated in valvular remodeling.
- Mechanisms like mechanotransduction and osteogenic calcification are plausible but uncharacterized in RHD.
Conclusions:
- SGLT2 inhibitors present a promising hypothesis for RHD treatment.
- Further research, including SGLT2 expression validation in RHD tissue and clinical trials, is essential to confirm therapeutic potential.
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