Decoding atrial mechanics: human atrial slices as a model for atrial disease

Atrial dysfunction plays a critical role in cardiac disease, particularly during arrhythmias and in heart failure, where impaired atrial contraction can compromise cardiac output. Yet, models that allow direct assessment of human atrial biomechanics remain scarce. Living myocardial slices (LMS) have the potential to revolutionize preclinical cardiac studies by preserving native architecture and performance in near-physiological environments, offering a patient-specific platform to investigate atrial function. To address this gap, we present the first functional analysis of human atrial LMS across diverse disease phenotypes, including healthy tissue, heart failure (HF), rhythm disorders, and atrial dilatation. Using the largest human atrial LMS dataset to date, containing 250 slices from 48 patients, we assessed contractile force, kinetics, force-frequency relationships, and refractoriness during the acute culture phase. Atrial slices exhibited faster contractions than ventricular LMS. HF and dilated atria showed reduced contractile force and prolonged contraction and relaxation, whereas slices from patients with atrial fibrillation displayed preserved or enhanced kinetics with increased variability in refractoriness. Structural analyses confirmed elevated fibrosis in all disease groups, along with disease-specific alterations in cellular morphology and tissue organization. Together, these findings provide a reference framework for human atrial biomechanics, thereby positioning LMS as a promising model for studying atrial pathophysiology in vitro.<b>NEW & NOTEWORTHY</b> Human atrial living myocardial slices (LMS) bridge the gap between clinical disease and tissue-level mechanistic insight. Using the largest dataset of human atrial slices to date, this study maps the biomechanical landscape of the atrium and reveals preserved disease-specific signatures in vitro. These findings position LMS as a promising platform for studying atrial pathophysiology and therapeutic development.