Background: Cardiac surgery is predominantly performed in older adults, a population in whom multimorbidity and accelerated biological ageing are highly prevalent. Accelerated biological ageing, driven by genomic instability, epigenetic drift, chronic inflammation and dysregulated immune function, has been linked to impaired post-operative recovery. Age-associated immune remodelling, including increased myelopoiesis, heightened pro-inflammatory cytokine production and reduced adaptive immunity, contributes to a state of inflammageing that may exacerbate myocardial injury following injury. Recent work from the Ob-CARD cohort (NCT0298009) has identified biologically distinct clusters of age acceleration, characterised by altered inflammatory and stress-response pathways within both haematopoietic stem cells and myocardial tissue. To investigate the effects of accelerated biological ageing on myocardial cellular heterogeneity and immune-cardiomyocyte interactions, we performed single-nuclei RNA-sequencing on myocardial biopsies. Differential expression and GO:BP analysis revealed cardiomyocytes from individual with high PhenoAge acceleration adopt a metabolically stressed phenotype, enriched for oxidative phosphorylation and translational programs, but depleted for muscle development, contraction and cardiac conduction pathways, including a less contractile cellular state. Parallel analysis of monocyte-derived and tissue resident macrophages demonstrate accelerated age-associated transcriptional reprogramming, including heightened inflammatory signalling, altered chromatin accessibility, and changes in secretome composition. Ligand–receptor communication modelling revealed that these macrophage alterations disrupt key signalling pathways governing cardiomyocyte contractility, maturation, and electrophysiological stability.