Journal of Development in Bioengineering and Biosciences

Atrial fibrillation (AF), the most common cardiac arrhythmia links to significant morbidity, mortality, and healthcare costs through typical risks like ageing, hypertension, and structural heart disease. Recent studies show chronic psychosocial stress, negative emotions, and mental health factors in AF susceptibility. This review integrates AF epidemiology, focusing on mental stress and adverse emotional states interacts with atrial electrophysiology. Key mechanisms include sympathetic upregulation, parasympathetic attenuation, HPA axis overdrive, inflammation, and myocardial remodelling. Observational data associate persistent stress with higher AF incidence yet causation and stress reduction effectiveness remain uncertain. Targeting modifiable psychosocial factors mat contribute to improve risk stratification management and quality of life.

Preclinical drug development faces inherent limitations associated with conventional models, such as two-dimensional cell cultures and animal models, which exhibit limited physiological relevance and contribute to high attrition rates in clinical phases. NAMs, including human organoids, organ-on-chip systems, microphysiological platforms, physiologically based pharmacokinetic modeling, omics technologies, and artificial intelligence, provide an integrated and predictive framework for the assessment of organ-specific toxicities, mechanistic characterization, and human extrapolation. These tools enable dose optimization, improved risk monitoring, and reduction in animal use. Nevertheless, challenges remain regarding functional maturation, experimental reproducibility, regulatory validation, and population representativeness. The strategic and combined application of NAMs constitutes an advanced preclinical ecosystem that complements traditional approaches and holds significant potential to enhance the safety and efficacy of drug candidates in development.