Outcomes of Branch Pulmonary Artery Stenosis in Williams Syndrome and Non-Williams Supravalvar Aortic Stenosis

Background 
The cardiovascular findings noted in both Williams syndrome (WS) and non-Williams (NW) supravalvar aortic stenosis (SVAS) are most often mediated by abnormal or deficient elastin (ELN). Branch pulmonary artery stenosis (BPAS) is the next most common lesion after SVAS. The prevalence, interventions for, and outcomes of BPAS in WS and NW SVAS has not been well-described.  
 
Aim 
Describe and compare BPAS intervention and outcomes in patients with WS and NW SVAS.  
 
Subjects and Methods 
We included  all  patients at our institution  with either WS or SVAS with negative testing for WS from 2003-2020.Patients with Alagille syndrome, Turner syndrome, isolated bicuspid aortic valve, postoperative acquired SVAS, or insufficient records were excluded. We compared the prevalence of BPAS in both groups, interventions for BPAS (surgical versus catheter-based), and freedom from intervention using Kaplan-Meier analysis with comparison by log rank.  
 
Results  
A total of 183 patients were included (87 WS, 96 NW SVAS) with median age at last follow up of 10.7 years (IQR 4.8 to 15.9). Of the NW-SVAS group, only 11 patients underwent testing for ELN pathogenic variants, of which 6 were positive. BPAS was present in more patients with WS (60%, n=52) compared to NW-SVAS (35%, n=34, p=0.001). However, intervention for BPAS was more common in patients with NW-SVAS (44% in NW-SVAS versus 23% in WS, p = 0.040). Interventions for BPAS included surgical patch augmentation in 11 patients (41%), balloon angioplasty +/- stenting of branch PA in 11 patients (41%) and both (surgical and catheter-based) in 5 patients (18.6%). Of those that underwent BPAS intervention, median age at first intervention was significantly younger in WS (0.7 years, IQR 0.4-1.1 years) compared to NW-SVAS (2.1 years, IQR 0.7-2.5 years, p= 0.019). While freedom from intervention was similar in both groups for the first 2 years of life (79% in WS, 79% in NW-SVAS), after age there were few new BPAS interventions in the WS group, but continued interventions in the NW-SVAS group (Figure 1A, post age 2 years log rank p<0.001). Fifty-five percent of first BPAS interventions in WS were surgical compared to 47% in NW-SVAS (p value= 0.691). Eleven patients (41% of all with BPAS) required reintervention for BPAS with no significant difference in time to reintervention between WS and NW-SVAS (log rank p=0.527). Reintervention more commonly occurred for BPAS in the NW-SVAS group than the WS group (Figure 1B, log rank p=0.019).
   
Conclusion  
While BPAS was more common in WS compared to NW-SVAS in our study, intervention for BPAS was more common in NW-SVAS. WS patients that survive without intervention in first few years of life are less likely to require intervention at later age. Need for re-intervention is more common after catheter based versus surgical angioplasty.