Background: Uncorrected atrial septal defects (ASD) are associated with atrial arrhythmias however little is known about the bi-atrial arrhythmia substrate in ASD patients and optimal rhythm management strategies remain unclear.
We hypothesised that the right atrium is important to atrial arrhythmogenesis in ASD patients and that 1) electrical and structural remodelling and 2) arrhythmia triggers/ectopic foci would be present in the right atrium of ASD patients. Additionally, we hypothesised that atrial remodelling may be reversible with ASD closure.
Methods: Comprehensive assessment of atrial electrophysiological function and structure and was undertaken in unclosed ASD patients and non-congenital heart disease AF control patients. Bi-atrial voltage mapping, effective refractory period (ERP) measurement and assessment of isoprenaline-induced atrial ectopy was performed at the time of ASD closure. Atrial late gadolinium enhancement cardiac MRI (CMR) was performed prior to ASD closure to quantify bi-atrial fibrosis. Control patients underwent the same protocol prior to and during AF ablation. Site of ambulatory atrial ectopy origin was assessed using Holter monitoring following invasive validation of three-lead p-wave axis morphology. One-year post closure, ASD patients underwent repeat right atrial electrophysiology studies and CMR assessment.
Invasive Electrical Assessment
Eighteen ASD and 18 control patients underwent electrophysiology studies. Right atrial mean voltage was significantly lower and proportion of low voltage (<0.5mV) significantly greater in ASD than control patients (p=0.01 and p=0.022). In ASD patients, mean voltage was significantly lower and proportion of low voltage areas significantly greater in the right atrium than the left atrium (p=<0.001 and p=0.003). Right atrial ERP was longer in ASD patients than control patients (p=0.021).
On 24-hour Holter monitoring right sided ectopy was more prevalent in ASD than control patients (p=0.038) and ectopic burden was associated with presence of atrial arrhythmias in ASD patients (p=0.04). During isoprenaline infusion right-sided ectopy was seen in 71% of ASD patients compared to 69% of controls (p=N/S) and bi-atrial ectopic foci were present in 43% of ASD patients and 31% of controls (p=N/S).
36 ASD and 36 control patients underwent bi-atrial CMR imaging. Right and left atrial fibrosis were both significantly greater in ASD patients than control patients (p<0.001). In ASD patients, fibrosis was significantly greater in the right atrium than the left atrium (p=0.010). Right atrial fibrosis burden and right atrial volume were both significantly greater in ASD patients with atrial arrhythmias than those without (p=0.037 and p=0.005).
Effects of Closure
To date, two patients have undergone repeat post-closure CMR and one patient has undergone repeat electrophysiology studies one-year post-closure (analyses pending).
Conclusion: Changes of electrical and structural remodelling in ASD patients predominate in the right atrium and in ambulatory patients right atrial ectopy is more common in ASD patients than control patients. A strategy of right-sided ablation as an adjunct to pulmonary vein isolation in ASD patients with atrial arrhythmias warrants investigation in a randomised controlled trial.