The Role of Elevated Wall Shear Stress in Progression of Pulmonary Vein Stenosis: Evidence from Two Case Studies

Peter E Hammer,Kerry Mcenaney,Kathy J Jenkins,Ryan Callahan,David M Hoganson,Christopher W Baird

doi:10.3390/children8090729

Abstract

Pulmonary vein stenosis is a serious condition characterized by restriction or blockage due to fibrotic tissue ingrowth that develops in the pulmonary veins of infants or children. It is often progressive and can lead to severe pulmonary hypertension and death. Efforts to halt or reverse disease progression include surgery and catheter-based balloon dilation and stent implantation. Its cause and mechanism of progression are unknown. In this pilot study, we propose and explore the hypothesis that elevated wall shear stress at discrete pulmonary venous sites triggers stenosis. To assess this theory, we retrospectively analyzed cardiac catheterization, lung scan, and X-ray computed tomography data to estimate wall shear stress in the pulmonary veins at multiple time points during disease progression in two patients. Results are consistent with the existence of a level of elevated wall shear stress above which the disease is progressive and below which progression is halted. The analysis also suggests the possibility of predicting the target lumen size necessary in a given vein to reduce wall shear stress to normal levels and remove the trigger for stenosis progression.

Highlights

Pulmonary vein stenosis (PVS) is a critical narrowing of one or more pulmonary veins that affects 1.7 per 100,000 children under the age of two [1]
balloon dilation (BD) of this left lower pulmonary vein (LLPV) and the somewhat less stenotic left upper pulmonary vein (LUPV) over the 5 years appeared to result in near normalization of wall shear stress (WSS) levels and resolution of the disease. This analysis of blood flow through pulmonary veins shows that WSS levels are elevated in vessels with known PVS and are in a range that has been shown to trigger neointimal hyperplasia in large veins
In the case of Patient 2 (Pt2), the stenting of the LLPV to 10 mm and follow-up BDs achieved durable lumen dimensions of 10.0 × 8.6 mm, quite close to the value of 10.8 mm predicted by this theory to result in normal WSS

Summary

Introduction

Pulmonary vein stenosis (PVS) is a critical narrowing of one or more pulmonary veins that affects 1.7 per 100,000 children under the age of two [1]. PVS can arise following surgical correction of abnormal pulmonary venous drainage in infants, or it can arise without apparent cause as a primary condition in normally connected vessels. Other origins include a surgical connection or sites where an external structure such as an airway impinges on a pulmonary vein. The disease can further progress to involve other branches of the same pulmonary vein, or to other pulmonary veins, resulting in pulmonary hypertension, heart failure, and death. A hallmark of the disease is recurrence or progression, even after relief of stenosis with surgery or catheter-based intervention. No treatments, including medical, surgical, or catheter based, are reliably effective in halting disease recurrence or progression. Limited understanding of the disease process and its underlying cause hinders the development of effective treatments

Methods

Results

Conclusion