Functional Reserve and Contractile Phenotype of Atrial Myocardium from Patients with Atrial Remodeling without and with Atrial Fibrillation

Atrial contractility and functional reserve in atrial remodeling (AR) without (AR/-AF) or with atrial fibrillation (AR/+AF) are not well characterized. In this study, functional measurements were performed in n=71 right atrial muscle strips obtained from patients (N=22) undergoing routine cardiac surgery with either no AR (left atrial (LA) diameter <40 mm and no history of AF (hAF)), AR/-AF (LA diameter =40 mm, no hAF), or AR/+AF (hAF and LA diameter =40 mm or LAEF < 45%). AR/-AF and AR/+AF were associated with a prolongation of half-time-to-peak (HTTP, p<0.001) and time-to-peak (TTP) contraction (p<0.01) when compared to no AR. This effect was seen at baseline and during ß-adrenergic stimulation with isoproterenol (ISO). Early relaxation assessed by half-relaxation-time (HRT) was prolonged in AR/-AF (p=0.03) but not in AR/+AF when compared to no AR at baseline, but this delay in relaxation in AR/-AF was attenuated with ISO. Late relaxation (tau) did not differ between AR/-AF and no AR but was consistently shorter in AR/+AF than no AR before (p=0.04) and during ISO (p=0.01), indicating accelerated late relaxation in AR/+AF. Relative force increase during ISO was higher (p=0.01) and more dispersed (p=0.047) in patients with AR/+AF. Relative adrenergic response was unaltered in myocardium from patients with AR/-AF and AR/+AF. In conclusion, AR/-AF and AR/+AF are associated with changes in myocardial inotropic reserve and contractility. The changes are particularly pronounced in patients with AR/+AF, suggesting that the progression from AR/-AF to AR/+AF is associated with progressive alterations in atrial function that may contribute to arrhythmogenesis.