Analysis of age-related left ventricular collagen remodeling in living donors: Implications in arrhythmogenesis

Highlights

• Collagen remodeling traits change from youth to adulthood, not from midlife onwards

• In humans, collagen remodeling traits relate with the biological age-pigment lipofuscin

• Beyond collagen amount, its distribution also influences ventricular arrhythmogenesis

• Consistent age-related remodeling was observed amid healthy farm pigs and living donors

Summary

Age-related fibrosis in the left ventricle (LV) has been mainly studied in animals by assessing collagen content. Using second-harmonic generation microscopy and image processing, we evaluated amount, aggregation and spatial distribution of LV collagen in young to old pigs, and middle-age and elder living donors. All collagen features increased when comparing adult and old pigs with young ones, but not when comparing adult with old pigs or middle-age with elder individuals. Remarkably, all collagen parameters strongly correlated with lipofuscin, a biological age marker, in humans. By building patient-specific models of human ventricular tissue electrophysiology, we confirmed that amount and organization of fibrosis modulated arrhythmia vulnerability, and that distribution should be accounted for arrhythmia risk assessment. In conclusion, we characterize the age-associated changes in LV collagen and its potential implications for ventricular arrhythmia development. Consistency between pig and human results substantiate the pig as a relevant model of age-related LV collagen dynamics.