Background: Atrial mechanical alterations are found in patients with atrial remodeling (AR) without or with concomitant atrial fibrillation (AF). Atrial functional reserve is a determinant of cardiac output, especially during periods of increased hemodynamic demand. However, intrinsic atrial contractility and functional reserve during β-adrenergic stimulation in AR without or with AF are not well characterized.

Methods: Functional measurements were performed in n=71 right atrial muscle strips obtained from patients (N=22) undergoing routine cardiac surgery with either normal atrial dimensions (no AR, i.e. left atrial (LA) volume index (LAVI) <34 ml/m² / LA diameter (LAD) < 40mm), AR without AF (AR/-AF), or AR with concomitant AF (AR/+AF) (categorized by clinical history, ECG and comprehensive echocardiography). Systolic and diastolic markers of contractility were assessed before and during β-adrenergic stimulation with isoproterenol (ISO). The study was approved by the local Ethics Committee of Charité (EA2/167/15).

Results: Patients with no AR had mean LAD of 36 ± 1 mm and LAVI of 28 ± 2 ml/m² mean ± SEM), whereas LAD and LAVI were increased in the AR/-AF group (LA diameter 42 ± 2 mm, LAVI 51 ± 11 ml/m²) and the AR/+AF group (LA diameter 44 ± 3 mm, LAVI 55 ± 12 ml/m²); all p<0.05. AR/-AF and AR/+AF were associated with a prolongation of half-time-to-peak (HTTP) (baseline: 61 ± 2 and 59 ± 2 vs. 50 ± 1 ms, p<0.001) and time-to-peak (TTP) contraction (baseline: 121 ± 4 and 121 ± 5 ms vs. 102 ± 2 ms, p<0.001) when compared to no AR. This effect was found before (at baseline) and during ISO treatment. Early relaxation assessed by time to half relaxation (HRT) at baseline was prolonged in AR/-AF (95 ± 5 ms vs. 84 ± 2 ms, p=0.03) but not in AR+AF (84 ± 2 ms vs. 84 ± 2 ms, p=ns) when compared to no AR, but this delay in relaxation in AR/-AF was alleviated with ISO. Late relaxation (tau, monoexponential fit following 50% relaxation) did not differ between AR/-AF and no AR but was consistently faster in AR/+AF vs. no AR before (56 ± 2 ms vs. 67 ± 3 ms, p=0.04) and after ISO (42 ± 2 ms vs. 56 ± 3 ms, p=0.01), indicating accelerated late relaxation. Furthermore, relative force increase during ISO was 55 ± 12 % in the no AR group, whereas it was numerically increased in the AR/-AF group (121 ± 39 %, p=ns), and significantly increased in the AR/+AF group (264 ± 90 %, p=0.001). Aside from that, variability in the ISO response (assessed by standard deviation per patient) between groups was found: Heterogeneity was 21.7 ± 8 % in the no AR group, whereas it was numerically higher in the AR/-AF (46.4 ± 20 %, p=ns), and significantly higher in the AR/+AF group (110.4 ± 68 %, p=0.047). Overall, systolic and diastolic adrenergic response was unaltered in AR/-AF and AR/+AF.

Conclusion: AR/-AF and AR/+AF are both associated with changes in myocardial inotropic reserve and contractility. The changes are particularly pronounced in patients with AR/+AF, suggesting that the progression of AR from normal atrial configuration to AR/-AF to AR/+AF is also associated with progressive alterations in the atrial functional adrenergic reserve that may contribute to arrhythmia formation.