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Heart disease remains a leading cause of mortality worldwide, posing a significant challenge to global healthcare systems. Traditional animal models and cell culture techniques are instrumental in advancing the understanding of cardiac pathophysiology. However, these methods are limited in their ability to fully replicate the heart's intricate functions. This underscores the need for a deeper investigation into the fundamental mechanisms of heart disease. Notably, cardiac pathology is often influenced by systemic factors, with conditions in other organs contributing to disease onset and progression. Cardiac-focused multi-organ chip technology has emerged to better elucidate these complex inter-organ communications and address the limitations of current in vitro models. This technology offers a novel approach by recreating the cardiac microenvironment and integrating it with other organ systems, thereby enabling more precise disease modeling and drug toxicity assessment. This review provides a comprehensive overview of the heart's structure and function, explores the advancements in cardiac organ chip development, and highlights the applications of cardiac-focused multi-organ chips in medical research. Finally, the future potential of this technology in enhancing disease modeling and therapeutic evaluation is discussed., (© 2025 Wiley‐VCH GmbH.)

Heart-on-a-chip (HoC) devices have emerged as a powerful tool for studying the human heart's intricate functions and dysfunctions in vitro. Traditional preclinical models, such as 2D cell cultures model and animal model, have limitations in accurately predicting human response to cardiovascular diseases and treatments. The HoC approach addresses these shortcomings by recapitulating the microscale anatomy, physiology, and biomechanics of the heart, thereby providing a more clinically relevant platform for drug testing, disease modeling, and personalized therapy. Recent years have seen significant strides in HoC technology, driven by advancements in biomaterials, bioelectronics, and tissue engineering. Here, we first review the construction and on-chip detection in HoC. Then we introduce the current proceedings of in vitro models for studying cardiovascular diseases (CVD) based on the HoC platform, including ischemia and myocardial infarction, cardiac fibrosis, cardiac scar, myocardial hypertrophy and other CVD models. Finally, we discuss the future directions of HoC and related emerging technologies., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors have read and approved the final manuscript. Competing interests: The authors declare no potential competing interest., (© 2024. The Author(s).)