Elastin arteriopathies are the primary causes of congenital supravalvular aortic stenosis. The most notable example of this condition is Williams-Beuren syndrome, also known as Williams syndrome. Elastin dysfunction leads to reduced arterial elasticity, increasing stiffness. This triggers smooth muscle cell migration and proliferation, resulting in hypertension and vascular stenosis. There are two forms of presentation: discrete and diffuse. The discrete form occurs in 75% of cases and involves the sinotubular junction, which acquires a “hourglass” morphology. Diffuse forms are more severe, potentially affecting a significant portion of the arterial tree, including coronary arteries, in extreme cases. Pulmonary artery involvement is present in approximately half of the patients, though it is usually well tolerated and rarely prompts surgical intervention. Surgical indication is typically determined by left-sided stenosis at the level of the ascending aorta, mid-aortic syndrome, aortic valve, coronary, renal, or visceral arteries. Once diagnosed, prompt action is advised, as the risk of sudden death is increased by 25–100 times compared to the general population. 

The aim of the study was to evaluate surgical outcomes in this rare condition. A systematic review was conducted, including observational studies with over 2 years of follow-up and cohorts exceeding 20 patients. Both pediatric and adult populations were analyzed. Risk factors, event rates, and survival curves were examined to perform a 30-year microsimulation study, predicting life expectancy. 

A total of 23 publications involving 1,472 patients and 13,125 patient-years with a median follow-up of 6.3 years were included. The mean age at initial repair was 4.7 years. Nearly half of the cases utilized the McGoon technique, involving the implantation of a single enlargement patch. Early mortality was 4.2%, and late mortality was 0.61% per patient-year. Based on the microsimulation, a patient undergoing surgery at 4.7 years of age was estimated to have a life expectancy of 90% compared to the general population. At 30 years, these patients faced an 8% risk of myocardial infarction and a 30% risk of reintervention, with one-third attributable to repair dysfunction. 

The authors concluded that, at 30 years, patients operated on for congenital supravalvular aortic stenosis exhibit lower survival compared to the general population, with a significant reintervention risk. Therefore, they recommend continued cardiovascular monitoring in these patients, emphasizing the diagnosis and treatment of residual stenosis and coronary obstruction. 

COMMENTARY: 

It is a mistake to group all supravalvular aortic stenosis under the same category, as each condition involves distinct obstruction patterns of varying severity. First, it is essential to distinguish whether the underlying pathology is an elastin dysfunction arteriopathy (with Williams syndrome being the classical etiology), Shone complex (which may involve multilevel left heart obstruction), or iatrogenic, resulting from an overly ambitious closure following an aortotomy. In Williams syndrome, the severity and association of systemic arterial lesions determine the patient’s short-term survival and potential long-term complications. This condition demands perioperative and intraoperative decisions that can drastically alter the planned surgical course. It is crucial to judiciously enlarge clinically significant stenotic areas while minimizing ischemic time. Consequently, various surgical techniques exist, with no clear consensus on the superior method. Options include single-patch repair (McGoon technique), two-patch repair (Doty technique), three-patch repair (Brom technique), and the Myers interdigitating aortoplasty, which avoids patch use. 

One of the most challenging decisions is whether to enlarge the coronaries, as no diagnostic test definitively clarifies coronary flow compromise in these patients. This explains the high rates of perioperative myocardial infarction reported in the literature. Following stenotic relief, it may be assumed that coronary flow would improve. However, coronary insufficiency in these patients is counterintuitive: elevated aortic root pressure distends the lumens of thickened coronaries, preventing collapse. Treating the supravalvular stenosis alone reduces aortic root pressure, potentially collapsing coronary lumens. A high index of suspicion for coronary involvement and a comprehensive evaluation are necessary. Aggressive and diffuse disease presentation likely indicates coronary involvement as well. Reaching and executing this decision is far from straightforward. 

Another limitation worth mentioning is the quality of the studies underpinning the meta-analysis and microsimulation. Due to the rarity of this disease, most literature comprises small-sample retrospective observational studies. This diminishes statistical power, which is further weakened by combining heterogeneous pathologies and pooling pediatric and adult populations. 

In conclusion, any study on rare conditions requires tremendous effort, which must be acknowledged and appreciated. However, making 30-year predictions is akin to building a house of cards. 

REFERENCE:

Meccanici F, Notenboom ML, Meijssen J, Smit V, van de Woestijne PC, et al. Long-term surgical outcomes of congenital supravalvular aortic stenosis: a systematic review, meta-analysis and microsimulation study. Eur J Cardiothorac Surg. 2024 Jan 2;65(1):ezad360. doi: 10.1093/ejcts/ezad360.