With great pleasure, we announce a new Special Issue on Cardiovascular Disease in the Mammalian Genome.

In recent decades, cardiovascular medicine has made great strides and thanks to effective drugs and treatments, patients have a longer and improved quality of life (Khazanie et al. 2017). Notwithstanding these striking advances, cardiovascular disease remains the number one cause of death worldwide (Tsao et al. 2023). The incidence of heart failure, cardiac arrhythmias, coronary artery disease/heart attack, valvular heart disease and congenital heart defects remains high compared to other common diseases such as cancer and diseases of the respiratory system. In addition, the impact of the COVID-19 pandemic on the care of cardiovascular patients with severe or even critical COVID-19 courses, up to and including intensive care requirements, was greater in patients with pre-existing high-risk diseases such as hypertension, obesity, diabetes, or heart failure (Raisi-Estabragh and Mamas 2022). This underscores why combating these diseases in particular through early prevention, detection and their consequent treatment is of paramount importance.

The possibilities of innovations in cardiac medicine are far from exhausted. New approaches are needed and although they may already exist in basic research, they rarely find their way into clinical practice. The reasons for this are manifold. However, it is precisely this wide-ranging basic research that is important in order to advance diagnostic and therapeutic procedures, to better understand disease processes before they unfold their damaging effects on the heart or blood vessels, to detect them earlier, and to prevent them with the help of targeted therapies.

This Special Issue is intended to create a platform for a wide range of human and model organism studies dedicated to heart-related basic research with the overarching goal of initiating new developments in heart medicine.

The prelude is made by reviews on standardized high-throughput cardiovascular phenotyping with a link to metabolism in mice, the standardization and future of preclinical echocardiography, three-dimensional microCT imaging of mouse heart development and electrocardiography with special emphasis on telemetry in mice. Following these are important guideline articles on newly determined electrocardiography reference ranges and artificial intelligence-based echocardiography evaluation in mice. A historical survey rounds off this prelude with a review entitled “The second heart field: the first 20 years”. In parallel with articles on mouse models such as “Knockout of the Complex III subunit Uqcrh causes bioenergetic impairment and cardiac contractile dysfunction” and “Knockout mouse models as a resource for the study of rare diseases”, a couple of very insightful articles describe the utility of cross-species data: “Dog models of human atherosclerotic cardiovascular diseases” and “Fins, fur and wings: The study of Tmem161b across species, and what it tells us about its function in the heart”. This section on model organisms in cardiac research is complemented by the description of a new heart atlas based on a comparative single-cell analysis of the adult heart and the coronary vessels.

With respect to human-based research, a number of very exciting congenital heart diseases are addressed, with special emphasis on the use of mouse models, in articles describing the role of neointimal hyperplasia in systemic-to-pulmonary shunts in children with complex cyanotic heart disease, mouse models of spontaneous atrial fibrillation, transcriptome studies of inherited dilated cardiomyopathies and telemedical monitoring in patients with inborn cardiac disease. The Special Issue closes with a review article enriched with experimental data about a rationale for considering heart/brain axis control in neuropsychiatric disease and an outlook beyond cross-species models using cardiac organoids (“Promises and challenges of cardiac organoids”) and their future possibilities and applications in the field of cardiac research.