Table 1.

Evidence-source directness framework for mechanistic statements about atrial fibroblast metabolism.

Level	Evidence source	Permitted inference	Principal limitation
A	Human atrial fibroblasts with cell-specific functional evidence	Direct support from isolated human atrial fibroblasts or fibroblast-resolved human atrial preparations when the relevant pathway or function is measured or perturbed.	Culture adaptation, sampling bias, loss of tissue context, or incomplete in situ validation may remain.
B	Human atrial tissue or descriptive cell-resolved atlases	Direct support for atrial pathology, association, spatial localization, or fibroblast state in human tissue without fibroblast-specific functional perturbation.	Bulk or histological data do not establish cell specificity; descriptive single-cell or single-nucleus data do not establish causality or function.
C	Atrial animal models	Supports atrial mechanisms and intervention effects in vivo or in animal atrial fibroblasts.	Species and model differences limit direct human inference.
D	Ventricular or general cardiac fibroblasts	Supports plausibility for cardiac fibroblast biology.	Requires chamber-specific extrapolation to the atrium.
E	Extracardiac fibroblasts	Supports a potentially conserved fibroblast mechanism across organs.	Requires organ- and disease-context extrapolation.
F	Reduced experimental systems	Supports mechanistic possibility in co-culture, engineered tissue, isolated coupling, or computational models.	Cannot establish quantitative importance in the intact human atrium.

Categories A–F indicate the directness of evidence for fibroblast-specific mechanistic inference, not methodological quality. Evidence outside the atrial/cell-specificity framework is not assigned a category. nonFB, mechanistic evidence from cardiac non-fibroblast cells.