A Size Adjustable Pulmonary Valve Implant for Pediatric Applications

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Abstract Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart defect, occurring in 1 in every 3600 live births and affecting almost 10% of all children born with congenital heart disease. Contemporary management of ToF has evolved to elective complete surgical repair in early infancy, with perioperative mortality rates of <2%. Despite these advances, surgical augmentation of the right ventricular outflow tract remains a significant challenge. To date, transannular patch reconstruction, which involves disruption and enlargement of the pulmonary valve annulus, has been the most widely used repair strategy. However, a critical deficiency of this technique is the loss of structural integrity of the valvar apparatus, leading to chronic severe pulmonary insufficiency. Longitudinal data demonstrates severe pulmonary insufficiency often leads to progressive right ventricular dilation and biventricular dysfunction, leaving repaired ToF patients at significant risk of late adverse events, including development of ventricular arrhythmias, biventricular heart failure, and sudden cardiac death. To avoid these deleterious late outcomes, the majority of repaired ToF patients undergo eventual pulmonary valve replacement. The clinical pendulum is now shifting towards earlier valve replacement as it becomes increasingly evident that repaired ToF patients often develop significant right heart dysfunction several years before the onset of clinical symptoms. However, the unfortunate reality is that valve replacement options for small children are extremely limited. Existing prostheses often fail early, and, are universally unable to accommodate somatic growth of the child. Surgeons have attempted to address this urgent problem by implementing pulmonary valve-sparing repair strategies in children with ToF. Yet, emerging data from our institution demonstrates that most ToF patients who undergo valve-sparing repair develop early and progressive pulmonary insufficiency. Early loss of valve competency in ToF remains the Achilles heel of contemporary surgical management, and, critically, this unsolved problem leaves thousands of patients at ongoing risk of serious late adverse events. To address this urgent clinical problem, we propose to leverage promising simulation-based work from our group demonstrating venous-like valves remain competent across a wide range of vessel sizes, along with advances in stent technology and emerging biomaterials, to develop a growth-accommodating pulmonary valve replacement device to be implanted at the time of primary ToF repair. We propose two Specific Aims: Aim 1: Design an expandable, stent-mounted two-leaflet pulmonary valve replacement device that is capable of maintaining function across a wide range of diameters. Aim 2. Evaluate the feasibility of in vivo device expansion to accommodate somatic growth of the native pulmonary valve annulus in a growing ovine model. Achievement of this goal would represent a paradigm-shifting advance in the care of ToF patients, and, ultimately, would benefit any child who requires valve replacement early in life.