The Ross procedure has long been seen as an optimal operation for a select few. The detractors of it highlight the issue of an additional harvesting of the pulmonary artery, subjecting the native PA to systemic pressures and the need for reintervention as reasons to avoid it. However, the PA is a living tissue and capable of adapting and remodeling to growth. We therefore review the current evidence available to discuss the indications, contraindications, harvesting techniques, and modifications in a state-of-the-art narrative review of the PA as an aortic conduit. Due to the lack of substantial well-designed randomized controlled trials (RCTs), we also highlight the areas of need to reiterate the importance of the Ross procedure as part of the surgical armamentarium.
The use of the pulmonary autograft (PA) as a substitute for aortic valve and root replacement (AVR/AVRR) was initially proposed by Donald Ross, and subsequently, it has been the subject of large observational studies and randomized controlled trials (RCTs) [
The PA is relatively easily harvested and can be inserted without significant mismatch in size with the aortic valve and leads to few early site-related adverse events, one of all being endocarditis [
Despite encouraging results, the use of the PA has been limited worldwide. This may reflect a resistance to change from the widely accepted gold standard of aortic valve replacement (which is performed using conventional mechanical or stented xenograft prostheses. Therefore, the implant of these most commonly used substitutes presents a short and familiar learning curve and at same time is easily reproducible by the vast majority of cardiac surgeons [
Another point of heated discussion concerns the necessity to adapt the positioning of the PA in relation to the young age of the patient that is a perceived as a concern for the dilation of the neoaortic root and the consequent valve insufficiency leading for the dilation of the left ventricle. The latter requires additional surgical skills due to the involvement of the failed pulmonary autograft and homograft [
Finally, until recently, there has been a lack of persuasive evidence supporting a change in practice towards the extensive use of the PA as the ideal substitute for aortic valve disease. In this regard, the recent publications of large series evaluating the outcomes for more than 20 years on the use of the PA, either for the subcoronary or miniroot strategy by Sievers et al. and Nappi et al. [
Large propensity-matched observational studies have shown that the average survival in patients in whom the PA was used as substitute to AVR is longer into the second postoperative decade after the Ross procedure [
A comprehensive investigation that screened a large number of studies decidedly established the superiority of the Ross procedure [
On the contrary for 3 studies [
We are unaware of any randomized trials that have compared the Ross procedure to bioprosthesis AVR for severe aortic valve disease (S-AVD). However, evidence from one recent patient-level meta-analysis [
A growing number of studies comparing recipients of the Ross procedure and other AVR options in adults have been performed. 1 RCT [
Nowadays, there is a remarkable body of evidence to support the use of the Ross procedure, as it appears to offer an additional survival benefit over mechanical AVR. Indeed, more than 4 years ago, a propensity-matched cohort included 416 young and middle-aged adults with follow-up duration exceeding a mean of 14 years and reported a significant reduction in the hazard ratio (HR) for cardiac- and valve-related mortality in patients who received the Ross procedure (
Another study from Buratto included 1928 patients undergoing isolated mechanical AVR and 392 with the Ross procedure, which were evaluated with a risk-adjusted analysis and with follow-up duration exceeding 25 years [
The Ross procedure is a valuable option to treat both congenital and acquired disease of aortic valve and the left ventricular outflow tract. The pulmonary autograft can be implanted using 2 methods: the subcoronary implantation or free-end technique [
In the miniroot technique, the pulmonary valve is transposed into the aortic position with its pulmonary trunk so that the PA is withdrawn from the infundibulum of the right ventricle, scrupulously respecting its morphology. The pulmonary infundibulum consists mostly of the conal or infundibular septum, which separates the pulmonary valve from the aortic and tricuspid valves. We still recognize a second part which is the anterior extension or division of the trabecula septomarginalis while the third, smaller part is a superior extension of the trabecular septum.
The miniroot technique is the most used procedure and included complete preservation of pulmonary valve and pulmonary trunk with the need to coronary artery reimplantation [
Due to the different geometry and morphostructure of the aortic and pulmonary root (different commissural size and distribution), subcoronary implantation can be technically challenging, especially in patients with aortic insufficiency or bicuspid/unicuspid aortic valves. In addition, this approach is not possible when Ross’s operation is the preferred operation for the congenital patients in the phase of pediatric growth. For this reason, the free-standing aortic root replacement (miniroot technique) has been the most used technique [
The major concern with the use of pulmonary autograft used as miniroot implant is the increased risk of late pulmonary autograft dilatation due to the exposure of the full root to systemic pressures [
To overcome the PA expansion and avoid potential risk of reoperation for autograft failure, a number of technical modifications have been proposed, but there are currently no standard recommendations for their use. Three different approaches are customary in higher volume center, but data that support the effectiveness on the long-term results of these techniques are lacking. The approach of inclusion of the PA within the patient’s aortic root allows autograft to have a protection against the adverse effect of systemic pressure over time [
However, concerns remain that any observational study is not without the potential risk of drawing skepticism for a surgical indication. In this regard, confusion can be generated in a form of selection bias that is independent of whether the elements provided in the study are aggregated data, propensity-matched, or processed with a multivariable analysis. It is logical to hypothesize that although the efficacy and safety of the Ross procedure can be partly explained by careful patient selection, it is more likely attributable to intrinsic characteristics of the PA that make it decidedly unique for the biomimetic characteristic of living tissue thus highlighting its hemodynamics and biological-adaptive behavior. Despite convergent evidence demonstrating superiority in long-term results with the use of the Ross procedure over the usage of other operation for AVR- including data from a randomized controlled trial [
The Achilles heel of the PA replacing the AVR is the expansion of the vessel wall of the conduit after transposition into the left circulatory system where it is subjected to a higher arterial pressure, with a consequent decrease in the competence of the pulmonary valve and consequent increase in valve regurgitation [
In young or middle-aged patients, the evidence has established that the Ross procedure offers a lasting solution, particularly in the female population [
Although advances in prosthetic manufacturing have allowed the use of new-generation mechanical valves, it is potentially less thrombogenic, and lower international normalized ratio targets are required; however, self-monitoring of oral anticoagulants is still necessary [
From the results provided in the population of patients aged between 50 and 60 years, it is evident that the Ross procedure finds its optimal indication in people who, due to the absence of obvious comorbidities, are certainly more likely to benefit from the use of the pulmonary autograft. These patients had specific demographic, morphological characteristics and the absence of previous pathologies in their clinical history. In this respect, they had an expected life expectancy of 15 years, an active lifestyle, favorable anatomy, the absence of other major concomitant heart disease, and poor comorbidity.
Contraindications to the use of the Ross procedure are preoperative aortic regurgitation, an aortic ring of ≥27 mm, and pulmonary size mismatch [
What are then the modern indications for the use of the Ross procedure for AVD, and what do the recent studies add to our knowledge? We believe that the use of PA should be considered when planning any aortic valve and root surgery, given its characteristic of living tissue that corresponds to somatic growth, low risk of dimensional mismatch, versatility in achieving efficacy and safety for any type of operation on the aortic valve and on the aortic root, its perioperative safety, comparable to conventional mechanical and biological valves, and its late duration as a valve substitute, now clearly demonstrated, superior to traditionally used prostheses. Even the presence of a pathological bicuspid aortic valve today cannot be considered a contraindication. The study by Poh et al. [
Without doubt, the option for Ross procedure, although performed with an external reinforcement, is indicated in young patients with BAV and an aorta with a maximum diameter of 40 mm who do not have a hereditary pathology of the connective tissue or of the aorta. As reported below, the condition for the choice of the PA as substitute is conditioned by the use of surgical techniques that allow modified Ross procedures with the use of various external supports aimed at stabilizing the sinotubular junction and thus minimizing the risk of late aortic insufficiency and PA dysfunction. Overall, the choice of PA and surgical strategy for Ross procedure is based in part on evidence of comorbidities, ethical consideration, skill, and experience. To optimize outcomes in the population receiving the use of the Ross procedure and avoid the autograft failure, some considerations are needed on the knowledge of coexisting conditions that limit life expectancy to <15 years such as chronic dialysis in renal failure or radiation-induced valve disease. Also, some autoimmune diseases, for example, lupus erythematosus or rheumatoid arthritis, can raise concerns about the functional duration of the PA. Unquestionably, today, we have gained adequate knowledge of when to choose the Ross procedure and when it is deemed appropriate for the right patient and how to perform it perfectly. For example, the data provided by the current literature do not identify the use of PA as an appropriate choice in patients with rheumatic disease [
The concern related to the use of pulmonary autograft in aortic position is the potential long-term failure of the 2 valves, aortic and pulmonary. For many surgeons, this represents the Achilles heel of the Ross procedure and can certainly be deterrent to its widespread use. In fact, a patient who initially exhibits single-valve disease may subsequently require repeat surgery to treat two diseased valves. As noted by Stulak et al. [
For this reason, the problem of the longevity of the biological substitute is a priority, trying to give reasonable and favorable solutions to avoid adverse complications. Primary leaflet failure and dilation of the annulus, Valsalva sinuses, or sinotubular junction may occur in the patient who has an indication for a second operation after a Ross procedure for pulmonary autograft failure [
Associated with autograft failure, there is a risk of pulmonary homograft dysfunction which is used to reconstruct the ventricular-pulmonary outflow tract. The failure of pulmonary homograft is mainly manifested by the onset of an increasing valvular and supravalvular pulmonary stenosis which occurs more frequently at the level of the distal anastomosis and appears to be linked to an inflammatory activity [
Evidence based on follow-up of patients (
The ideal substitute to use for the reconstruction of the right ventricular-pulmonary trunk has been the reason of passionate discussion because the choice of the conduit can decisively affect its durability. Evidence shows that the duration over time of the pulmonary autografts is greater than that of the aortic homografts when they are implanted in the pulmonary position [
The choice of using cryopreserved pulmonary homografts was preferred for a long time because homografts were considered the ideal available substitutes for right ventricular outflow tract reconstruction [
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We evaluated the effect of reinforced and nonreinforced Ross procedure on long-term echocardiographic outcomes in 66 patients who received a PA for aortic valve surgery. The results are clearly delineated in Figure
(a) Survival of the reinforced vs. nonreinforced Ross procedure. (b) Freedom from reoperation of the reinforced vs. nonreinforced Ross procedure. Reproduced with permission from Nappi et al.
The experimental project Ross is a European alliance of investigators who aim to provide the basis for studying how to prevent the expansion of pulmonary autograft used in aortic valve surgery. The project was initiated in January 2011 and is achieved with collaboration of the Department of Cardiac Surgery of Centre Cardiologique du Nord and la Pitie Salpetriere Hospital. The first results were presented and discussed in June 2013 at the annual meeting of the Heart Valve Society in Venice, Italy [
The primary objective of Ross’s experimental project was to combine the individual data of the experimental animal model by comparing nonreinforced and reinforced pulmonary autograft as ideal substitutes for aortic valve surgery. Using an experimental model of growing sheep based on the simulation of the Ross operation, the experimental project Ross has estimated that the analysis of the results would have detected significant differences in the pulmonary autograft morphostructure at 6-month follow-up. The pulmonary autograft was inserted in the descending aorta while the right ventricle outflow tract was reconstructed with a fresh homograft from another lamb of the same age and weight or native pericardial neoconduit [
To date, in all the reported studies, the comparison between reinforced and nonreinforced pulmonary autograft did not consider the somatic growth variable which is fundamental when the Ross operation is performed during the patient’s growing age. Echocardiographic findings were largely undersized to assess differences in clinical events. Although the rate of superior expansion of the nonreinforced pulmonary autograft was established, there was no available evidence on any potential clinical benefit for the late outcomes.
The results were presented and discussed in June 2013 at the annual meeting of the Heart Valve Society in Venice, Italy [
(a) Semiresorbable cross-linked prosthesis composed by two layers: (1) resorbable polydioxanone, (2, 3) nonresorbable expanded polytetrafluoroethylene. (b) The prosthesis is used to reinforce the implanted pulmonary autograft that replaced the diseased aortic valve. The right side of the heart is reconstructed with a pulmonary homograft.
The use of pulmonary autograft in aortic valve surgery preserves, as living tissue, the structural and functional unity of the neoaortic root favoring better long-term clinical outcomes. The PA offers a continuous mediated living tissue activity that cannot be ensured by any other valve substitute with nonliving tissue characteristics. Although homografts have shown long-term viability, from a mechanical standpoint, they have proven to be inferior to pulmonary autografts [
The increased distensibility of viable pulmonary autograft is associated with recognized adaptive remodeling when the PA is transposed to an aortic position under systemic loading, thus mimicking the highly sophisticated anatomy and function of the native aortic root [
We have enhanced the remodeling capacity of the PA and at the same time reduced the negative effect of systemic pressure on the vessel wall using a semibioresorbable vascular scaffold that combined the polydioxanone to expanded polytetrafluoroethylene (BVS/PDS-e-PTFE) [
We have shown that the interaction between temporary bioresorbable reinforcement and pulmonary autograft has orchestrated a complex vascular remodeling process based on a balance between inflammation and production of extracellular matrix resulting after biomaterial resorption, in a “neovessel” which has characteristics similar to the aorta but is still biologically alive and capable of growing. The use of resorbable polyester was also associated with higher production of new extracellular matrix that was mainly characterized by a higher content of elastin fiber in the PA, as well as by a more compact organization of collagen fibers in the elastic zone of the vessel. Interestingly, the metalloprotease MMP-9 was found to be overexpressed indicating an ongoing matrix remodeling process. In parallel, cell proliferation was found to be increased in this group as testified by the significantly higher percentage of Ki67-positive cells (26.89%, 68.4% in the nonreinforced vs. 51.55%, 69.7% in the reinforced group,
These findings offered a plausible biologic and biomechanical explanation to the observed advantage in clinical outcomes. A biocompatible reinforcement of the PA would therefore allow induction of an in vivo creation of a PA with morphostructural characteristics that allow improved tolerance to the hemodynamic load of the arterial system and to guarantee a harmonic increase in size during somatic growth [
To further guide the choice of valve selection, we have formulated an algorithm to guide clinicians based on the evidence available as shown in Figure
Algorithm for patient selection for aortic valve replacement. Ross procedure or conventional mechanical/biological prosthesis.
Although the impact of the Ross procedure on long-term survival has been proven in young and middle-aged adults with significant impact when matching that of the age- and sex-matched general population, large propensity-matched observational studies and meta-analysis failed to cement its place as the ideal aortic valve substitute. The use of pulmonary autograft in aortic valve surgery has provided solid evidence of better long-term freedom from death and valvular complications compared to other conventional aortic valve prostheses used for AVR. Evidence has suggested that the Ross procedure provides better results when performed in centers of excellence where high volumes of aortic root surgery are performed. Much has been learned in the past 50 years of the Ross operation practice about the use and behavior of pulmonary autograft transposed in aortic position, but we are still in the process of iterative learning with more research needed. Unfortunately, there is a lack of evidence due to the absence of well-designed RCTs comparing the Ross procedure to mechanical or biological valves. Furthermore, greater confirmatory results can be provided by randomized clinical trials with the use of biocompatible external reinforcements able to stimulate, guide, and improve the natural processes of biological remodeling of the graft and reaction to foreign materials while respecting tissue growth. These studies could be a turning point in solving some of the drawbacks of the Ross procedure. Nevertheless, a significant impulse can be given by the biomechanical studies performed on the heart valves and on the extracellular matrix with the application of finite element analysis [
The authors declare that they have no conflicts of interest.