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.

Aortic Valve Embryology, Mechanobiology, and Second Messenger Pathways: Implications for Clinical Practice

“…Prosthetic valve replacement may not sufficiently reproduce biology by restoring native valve function; meanwhile, the Ross procedure allows for a living, dynamic substitute, even showing growth abilities in children [120,121]. It has been correctly postulated that the pulmonary autograft possesses the ability to adapt to the systemic environment by a phenotypic switch to an aortic phenotype after the Ross procedure, as the pulmonary and aortic roots share a common embryological genesis-the conotruncus [122]. However, neural crest cells, compromised in congenital AS, are less commonly seen in pulmonary than in aortic roots in murine embryological studies [123].…”

Aortic Valve Embryology, Mechanobiology and Second Messenger Pathways: Implications for Clinical Practice

“…Prosthetic valve replacement may not sufficiently restore natural valve function, whereas the Ross procedure allows for a living substitute, even showing growth abilities in children (97,98). It has been correctly postulated that the pulmonary autograft possesses the ability to adapt to the systemic environment by a phenotypic switch to an aortic phenotype after the Ross procedure, as the pulmonary and aortic roots share a common embryological genesis -the conotruncus (99). Explanted autografts are populated by viable valvular interstitial and endothelial cells after several years(100).…”

Drivers of Vascular Growth and Remodeling: A Computational Framework to Promote Benign Adaptation in the Ross Procedure

“…On the other hand, if the deviation from the homeostatic state is too high, elastin and collagen damage and fragmentation occur, leading to tissue degradation [39,40,41,42]. In case of underloading, cardiovascular stress-shielding biologically leads to smooth muscle cell death and thinning of the vessel wall [4]. We assume that this deviation from homeostatic state is expressed by means of a deviation from the homeostatic Cauchy stresses inside the arterial wall, generally denoted by ∆σ.…”

“…The latter degenerates over time and often requires reoperation [3]. The Ross procedure presents an attractive alternative AVR technique in which the patient's own pulmonary valve replaces the aortic valve [4]. This so-called pulmonary autograft remains alive and can adapt over time, and is the only type of AVR that can restore the patient's long-term survival and quality of life [5,6].…”