The digital twin concept creates a computer model of a patient based on their individual health data, allowing simulation of disease progression and the predicted effects of different treatments. In cardiology, these models combine medical imaging, clinical records and biological information to build a virtual replica of a patient’s heart. In principle, clinicians could test therapies on that digital heart before applying them to the real patient.
Why sex differences in biology are crucial
The potential of the technology depends heavily on the quality and representativeness of the underlying data. If datasets do not adequately reflect biological differences between women and men, digital twins may produce inaccurate or incomplete predictions of disease course and therapeutic responses.
This issue is especially important for cardiovascular disease: the World Health Organization (WHO) estimates that cardiovascular diseases cause nearly 18 million deaths each year worldwide. Myocarditis, an inflammatory disease of the heart muscle, is estimated to affect about 1.8 million people annually, and in young adults it occurs more frequently in men — the literature typically cites a two- to fourfold higher incidence in males.
Research links these disparities to differences in immune responses, hormonal effects and the biological properties of cardiac tissue. If digital models are not built from data that reflect such diversity, predictive algorithms will struggle to forecast how a condition will develop in an individual female or male patient.
Research directions and European initiatives
Several European research groups are addressing these challenges. Researchers at Aix–Marseille University are developing patient-specific computer models of inflammatory heart disease within the MYOCAR3 project, supported by Civis Alliance, and have already observed sex-based differences in immune responses that may affect model development.
The European Virtual Human Twin Initiative (VHT), supported by the European Commission, aims to accelerate development of digital twin technologies for health. The SimCardioTest project focuses specifically on creating patient-specific cardiovascular models to improve diagnosis and treatment planning. These programs bring together engineers, clinicians and data scientists to better understand complex heart diseases.
The COST Action EU-SABV initiative is the first Europe-wide programme explicitly dedicated to integrating “biological sex as a research variable” across biomedical studies, with the goal of making research findings both scientifically robust and relevant to diverse patient groups.
Sex- and gender-sensitive medicine
The research movement known as sex and gender-sensitive medicine emphasizes that health status and treatment outcomes are shaped not only by biological sex but also by social and cultural factors. Some clinical centres, such as the University Hospital Zurich Heart Center, have set up dedicated cardiology consultations that are sensitive to sex differences. Researchers analyse international databases and gather new clinical data to clarify the roles of biological sex and social gender in cardiovascular disease.
Historically, biomedical research has been biased: in preclinical studies, the number of male experimental animals was about five times higher than females, a bias that complicates the representativeness of today’s datasets.
Conclusions: data quality and the future of personalized medicine
Digital twin technology offers significant opportunities for personalized cardiology: models could predict disease progression, enable virtual testing of therapies, and support patient-specific treatment plans. Yet the technology’s success ultimately depends on whether the underlying data capture the full diversity of human biology, including biological differences between women and men.
The promise of personalized medicine can be fulfilled only if digital twins are built on representative, sex-aware datasets. Achieving that will require international research collaboration, improved data-collection practices, and the integration of sex- and gender-sensitive approaches into both research and clinical care.
