Women’s Circulating Biomarkers and Blood Cells in Postmenopausal Cardiac Dysfunction

• Applicant: Professorin Dr. Isabel Deisenhofer
• Subject Area: Cardiology, Angiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 568938917

Menopause induces a complex systemic transition in women due to the progressive decline in reproductive hormones, increasing the risk of cardiovascular diseases, such as hypertension, dyslipidemia, heart failure (HF), and atrial fibrillation (AF). Premature menopause increases the risk of HF by 30% and AF by 10%. Notably, AF and HF with preserved ejection fraction (HFpEF) co-occur in up to 25% of at-risk women and share a closely intertwined pathophysiology. Women with AF present a higher incidence of HFpEF and a higher risk of stroke and mortality than men. However, identification of sexspecific biomarkers for improved risk stratification and personalized treatment remains an important unmet clinical need.Preliminary data in our established sheep model of premature menopause unraveled a striking link between hormonal changes, altered atrial/ventricular repolarization dynamics, perivascular tissue changes, diastolic dysfunction and altered thromboinflammation. Based on these findings, this project aims to identify multimodal signatures of electromechanical cardiac remodeling and thromboinflammatory changes driving HFpEF in women with AF in a translational setting. Our objectives are to: i) characterize blood cell function and cardiac phenotype changes associated with AF and menopause in our established sheep model ii) identify novel biomarkers using untargeted analyses of circulating biomolecules (metabolome, proteome, transcriptome including microRNA and free DNA) and iii) validate these biomarkers in a prospective cohort of postmenopausal women undergoing AF ablation to assess their predictive value for rhythm and HF outcomes.This research will improve our understanding of postmenopausal cardiac dysfunction and identify novel, sex-specific biomarkers for AF-HFpEF, potentially leading to personalized therapeutic strategies in women. The project builds on a long-term collaboration between The IHU Liryc (France) and the TUM University Hospital German Heart Center (Technical University of Munich [TUM], Munich, Germany).

• DFG Programme: Research Grants
• International Connection: France
• Cooperation Partner: Professorin Dr. Mélèze Hocini