Novel Quality Metrics for Assessing the Reproducibility and Translational Relevance of Mouse Transverse Aortic...

Transverse aortic constriction (TAC) is widely used in mice to study pressure overload-induced cardiac hypertrophy and heart failure. However, methodological variability limits reproducibility and complicates translation to human disease. We sought to develop and apply a set of quality metrics that evaluate reproducibility and translational relevance in contemporary TAC studies.

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we reviewed articles with new mouse TAC experiments published between January 1, 2023, and December 31, 2024, across 6 leading cardiovascular journals. Studies were assessed for predefined quality metrics: bias-reduction methods, reporting of TAC pressure gradients, exclusion of outlying gradients, early measurement of TAC severity and cardiac function, inclusion of female mice, and initiation of interventions ≥7 days post-TAC. Reported average peak instantaneous pressure gradients were summarized.

Eighty-nine articles met inclusion criteria. Most (69.7%) reported at least 1 measure to reduce bias. Only 24.7% reported TAC pressure gradients, and 7.9% excluded mice with outlying TAC severity. Early cardiac function was evaluated in 20.2% of articles, and 31.5% initiated at least 1 intervention ≥7 days post TAC. Female mice were included in 28.1% of studies, with greater inclusion in National Institutes of Health-funded articles. Reported average peak instantaneous pressure gradients varied widely (36.8-131 mm Hg).

Most contemporary TAC studies do not report or perform key parameters important for experimental reproducibility and translational validity. Adoption of standardized quality metrics, including routine pressure gradient measurement, early cardiac function assessment, delayed intervention timing, and inclusion of female mice, could improve the reproducibility and translational relevance of TAC research.