Understanding Pulmonary Autograft Remodeling After the Ross Procedure: Stick to the Facts

Abstract

The Ross, or pulmonary autograft, procedure presents a fascinating mechanobiological scenario. Due to the common embryological origin of the aortic and pulmonary root, the conotruncus, several authors have hypothesized that a pulmonary autograft has the innate potential to remodel into an aortic phenotype once exposed to systemic conditions. Most of our understanding of pulmonary autograft mechanobiology stems from the remodeling observed in the arterial wall, rather than the valve, simply because there have been many opportunities to study the walls of dilated autografts explanted at reoperation. While previous histological studies provided important clues on autograft adaptation, a comprehensive understanding of its determinants and underlying mechanisms is needed so that the Ross procedure can become a widely accepted aortic valve substitute in select patients. It is clear that protecting the autograft during the early adaptation phase is crucial to avoid initiating a sequence of pathological remodeling. External support in the freestanding Ross procedure should aim to prevent dilatation while simultaneously promoting remodeling, rather than preventing dilatation at the cost of vascular atrophy. To define the optimal mechanical properties and geometry for external support, the ideal conditions for autograft remodeling and the timeline of mechanical adaptation must be determined. We aimed to rigorously review pulmonary autograft remodeling after the Ross procedure. Starting from the developmental, microstructural and biomechanical differences between the pulmonary artery and aorta, we review autograft mechanobiology in relation to distinct clinical failure mechanisms while aiming to identify unmet clinical needs, gaps in current knowledge and areas for further research. By correlating clinical and experimental observations of autograft remodeling with established principles in cardiovascular mechanobiology, we aim to present an up-to-date overview of all factors involved in extracellular matrix remodeling, their interactions and potential underlying molecular mechanisms.

Keywords: Ross procedure; external support; extracellular matrix; mechanobiology; pulmonary autograft; remodeling.

Figure 1

The 3 main techniques of the Ross procedure. 1. Freestanding root replacement technique with implantation of the entire pulmonary root into the left ventricular outflow tract. 2. Subcoronary technique: implantation of the pulmonary valve only within the native aortic annulus. 3. Autologous/native inclusion technique with implantation of the pulmonary autograft within the native aortic wall to prevent dilatation. Figure reproduced from Sievers (4), journal ceased publication no permission could be requested.

Figure 2

Most commonly used strategies to externally support the freestanding pulmonary autograft. (A) External subvalvular annuloplasty and sinotubular junction (STJ) stabilization in patients with risk factors for autograft dilatation. (B) Wrapping of the entire autograft within a cylinder of vascular tube graft. Figure adapted with permission from Mazine et al. (19).

Figure 3

Classification of the failure mechanisms of the Ross procedure and correlation with El Khoury's functional classification of aortic regurgitation. AR, aortic regurgitation; SVD, structural valvular degeneration; NSVD, non-structural valvular degeneration. Illustrations adapted with permission from Boodhwani et al. (39).

Figure 4

The aortic annulus (red crescent) is embedded within the fibrous skeleton of the heart whereas the pulmonary annulus (blue crescent) consists of a freestanding rim of infundibular muscle lifting the pulmonary leaflets away from the interventricular septum. LVOT, left ventricular outflow tract; RVOT, right ventricular outflow tract. Figure adapted with permission from Ho (60).

Figure 5

Pressure-diameter behaviors for the healthy aortic and pulmonary root illustrating non-linear mechanical behavior. In the aortic pressure range of 80–120 mmHg (dotted lines), the pulmonary artery behaves very stiff, evident by the steep incline. Figure recreated using data available in the article by Nagy et al. (40).

Figure 6

Representative longitudinal sections through the sinus and leaflets of the pulmonary artery and aorta of a sheep weighing 60 kg. Also shown are the pulmonary autograft and homograft at 6 months post-operatively in a sheep who underwent the Ross procedure (weighing 43 kg at operation). Neo-vascularization in the base of the pulmonary autograft leaflet (white arrowhead) and added collagen on the adventitial side of the sinus wall (black arrowhead). The arterial wall and leaflet of the pulmonary homograft are thin and acellular. Elastica Von Gieson staining. Adapted with permission from Van Hoof et al. (123).

Figure 7

Overview of established and potentially involved mechanisms of pulmonary autograft wall remodeling in the Ross procedure. The + indicates an adaptive response, — indicates maladaptive remodeling. IEL, internal elastic lamina; SMC, vascular smooth muscle cell; ECM, extracellular matrix; MMP, matrix metalloproteinase; TGFβ, transforming growth factor β; (M)FBR, fibroblast/myofibroblast.

Figure 8

(A) Pulmonary autograft wrapped with a cylinder of microporous Dacron graft. (B) Personalized external aortic root support implant fashioned from porous, soft mesh. Figure adapted with permission from Carrel et al. (34) and Treasure et al. (150).