Technologies, Clinical Applications, and Implementation Barriers of Digital Twins in Precision Cardiology: Systematic Review.

Background: Digital twin systems are emerging as promising tools in precision cardiology, enabling dynamic, patient-specific simulations to support diagnosis, risk assessment, and treatment planning. However, the current landscape of cardiovascular digital twin development, validation, and implementation remains fragmented, with substantial variability in modeling approaches, data use, and reporting practices. Objective: This systematic review aims to synthesize the current state of cardiovascular digital twin research by addressing 11 research questions spanning modeling technologies, data infrastructure, clinical applications, clinical impact, implementation barriers, and ethical considerations. Methods: We systematically searched 5 databases (PubMed, Scopus, Web of Science, IEEE Xplore, and Google Scholar) and screened 330 records. Forty-two original studies met the predefined eligibility criteria and were included. Data extraction was guided by 11 thematic research questions. Mechanistic and artificial intelligence (AI) or machine learning (ML) modeling strategies, data modalities, visualization formats, clinical use cases, reported impacts, limitations, and ethical or legal issues were coded and summarized. Risk of bias was evaluated using a custom checklist for modeling studies, the Prediction Model Risk of Bias Assessment Tool (PROBAST) for prediction models, and the Risk of Bias in Non-Randomized Studies - of Interventions (ROBINS-I) for observational studies. Results: Most digital twins (29/42, 69%) relied on mechanistic models, while hybrid mechanistic-data-driven approaches and purely data-driven designs were less frequent (13/42, 31%). Only 18 studies explicitly described ML or AI, most often deep learning, Bayesian methods, or optimization algorithms. Personalization depended primarily on imaging (32/42, 76%) and electrocardiography or other electrical signals (18/42, 43%). Visualization was dominated (41/42, 98%) by static figures and anatomical snapshots. Clinically, digital twins were most commonly applied to therapy planning, risk prediction, and monitoring. Reported benefits focused on improved decision-making and therapy-related impacts, with occasional (8/42, 19%) reports of increased accuracy or faster diagnosis, but there was limited evidence for downstream improvements in patient outcomes. Key barriers included strong model assumptions and simplifications; high computational cost; data quality and availability constraints; limited external validation; and challenges in real-time performance, workflow integration, and usability. Explicit discussion of ethical, legal, or governance issues was rare (7/42, 17%). Conclusions: Cardiovascular digital twins show substantial potential to advance precision cardiology by linking personalized physiological models with clinical decision support, particularly for therapy planning and risk prediction in arrhythmia and heart failure. However, real-world implementation is constrained by methodological heterogeneity, restricted data and validation practices, limited openness of code and models, and sparse engagement with ethical and governance questions. Future research should prioritize standardized evaluation frameworks, robust clinical validation, interoperable and user-centered system design, and ethically grounded, patient-centered development to realize the full clinical value of digital twin systems.