Pulmonary Vein Stenosis Program

Building off our past research, we are now better understanding the cellular events that contribute to the development of PVS. For example, increased blood flow velocity caused by compressed or obstructed veins puts abnormally high stress on the cells that line pulmonary veins. This stress causes injury to the cells lining the blood vessel wall, causing remodeling, which leads to scarring at the openings of the pulmonary veins.

Our research team is now analyzing changes within affected cells and identifying molecular targets that will help create pharmacological treatment options.

The first breakthrough in treatment came after realizing PVS is not like other types of congenital heart disease (CHD). While other types of CHD don’t grow or come back, PVS does. This realization led our team of doctors, researchers, and surgeons to begin looking more closely at the substance that causes blockages in the pulmonary veins of children with PVS. They discovered it was similar to a type of cancer cell, called a desmoid tumor.

This led them to look at chemotherapy regimens as a way of treating PVS. In 2009, the team moved forward with a single-arm trial using two drugs (imatinib mesylate and bevacizumab) that were already being used in pediatric oncology. The research program very quickly evolved into a clinical program, as PVS families started hearing about it and wanted another treatment option. So far, the approach seems to be working, and the program continues to treat patients and get national referrals. The team published their results in The Journal of Pediatrics in 2018.

Our program believes that aggressive follow-up in the monitoring of patients leads to improved outcomes. Our dedicated nurse practitioner checks in with patients often to triage symptoms, and they run more frequent tests. This allows clinicians to find — and treat — any problems early. A 2021 study reviewed how one of our nurse practitioners managed the care of a 3-year-old patient with multi-vessel intraluminal PVS.

Over the years, the cardiac catheterization team has used its extensive experience in treating PVS patients, as well as angiography and intravascular ultrasound, to modify their approach to PVS in the catheterization lab. This has allowed them to achieve better, more effective dilations with traditional equipment.

The cardiac surgery team has also taken a new approach to the treatment of PVS by looking at each vein’s specific anatomy. A surgeon can choose the right intervention to improve the anatomy and geometry of an individual vein. In addition, the surgeons have discovered ways of suturing the veins to keep them open.

Prior to 2021, there were no studies that reported detailed clinical syndromic phenotypes and the potential role of genetics in PVS. But a study that year by Boston Children’s found that PVS can be related to certain genetic syndromes, including trisomy 21 and Smith-Lemli-Opitz. The researchers recommended that full evaluation for PVS should be considered in certain patients with these associated syndromes.

Our researchers evaluated the association between aspiration and poor treatment response in patients with intraluminal pulmonary vein stenosis. In a 2021 study, they found that aspiration is a risk factor for the potential development and progression of PVS. In particular, clinical aspiration and male gender were identified as two novel risk factors for patients with two-ventricle physiology who had a poor response to multimodal PVS treatment that included imatinib mesylate as an antiproliferative agent. Their findings call for future studies to determine whether early identification and more aggressive treatment of aspiration can improve PVS outcomes.

There was a high incidence of in-stent stenosis (ISS) in 2019 when our researchers reported that sirolimus (rapamycin) can be helpful in slowing the growth rate of ISS in patients with PVS who were treated with stents. They found that systemic sirolimus slows the growth rate of ISS following stent implantation, compared to pre-treatment rates and when it was administered safely in a small number of pediatric patients with complex heart disease.

Our team researched 174 patients who underwent PVS repair over a 12-year span. Their findings, published in 2021 in The Journal of Thoracic and Cardiovascular Surgery, uncovered encouraging results: Anatomically focused surgical strategies aimed at straightening and shortening the pulmonary venous course are associated with improved survival.