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Archives of cardiovascular diseases
Volume 110, n° 4
pages 214-222 (avril 2017)
Doi : 10.1016/j.acvd.2016.09.008
Received : 18 April 2016 ;  accepted : 15 September 2016
Cliinical research

Pulmonary homograft stenosis in the Ross procedure: Incidence, clinical impact and predictors in long-term follow-up
Sténose d’une homogreffe pulmonaire au décours d’une procédure de Ross : incidence, impact clinique et prédicteurs du suivi à long terme
 

Laura Pardo González a, , Martin Ruiz Ortiz a, Mónica Delgado a, Dolores Mesa a, Rafael Villalba b, Sara Rodriguez a, Francisco J. Hidalgo a, Pedro Alados c, Jaime Casares c, Jose Suarez de Lezo a
a Department of Cardiology, Reina Sofia University Hospital, Córdoba, Spain 
b Regional Blood Transfusion Centre and Tissue Bank, Córdoba, Spain 
c Department of Cardiovascular Surgery, Reina Sofía University Hospital, Córdoba, Spain 

Corresponding author. c/Escultor Martínez Cerrillo 7 1°1, 14012 Córdoba, Spain.
Summary
Background

The Ross procedure is used in the treatment of selected patients with aortic valve disease. Pulmonary graft stenosis can appear in the long-term follow-up after the Ross intervention, but the factors involved and its clinical implications are not fully known.

Aim

To describe the incidence, clinical impact and predictors of homograft stenosis and reintervention after the Ross procedure in a prospective series in a tertiary referral hospital.

Methods

From 1997 to 2009, 107 patients underwent the Ross procedure (mean age: 30±11 years; 69% men; 21 aged<18 years), and were followed for echocardiographic homograft stenosis (peak gradient>36mmHg) and surgical or percutaneous homograft reintervention.

Results

After 15 years of follow-up (median: 11 years), echocardiographic and clinical data were available in 91 (85%) and 104 (98%) patients, respectively: 26/91 (29%) patients developed homograft stenosis; 10/104 (10%) patients underwent 13 homograft reintervention procedures (three patients underwent surgical replacement, three received a percutaneous pulmonary valve and one needed stent implantation). The other three patients underwent two consecutive procedures in follow-up; one died because of a procedure-related myocardial infarction. Rates of survival free from homograft stenosis and reintervention at 1, 5 and 10 years were 96%, 82% and 75% and 99%, 94% and 91%, respectively. Paediatric patients had worse survival free from homograft stenosis (hazard ratio [HR] 3.50, 95% confidence interval [CI]: 1.56–7.90; P =0.002), although there were no significant differences regarding reintervention (HR: 2.01, 95% CI: 0.52–7.78; P =0.31). Younger age of homograft donor was also a stenosis predictor (HR: 0.97, 95% CI: 0.94–0.99; P =0.046).

Conclusions

The probabilities of homograft stenosis and reintervention 10 years after the Ross procedure were 29% and 10%, respectively; only one patient had a reintervention-related death. Younger donor and recipient age were associated with a higher rate of stenosis.

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Résumé
Justification

La procédure de Ross est utilisée dans le traitement des valvulopathies aortiques de façon sélective. La sténose de la greffe pulmonaire peut apparaître lors du suivi au long cours ou au décours d’une intervention de Ross, les facteurs de risque et les implications cliniques ne sont pas parfaitement connus à ce jour.

Objectifs

Décrire l’incidence, l’impact clinique et les prédicteurs de la sténose d’une homogreffe pulmonaire ainsi que le taux de réintervention au décours d’une procédure de Ross dans une série prospective d’un centre hospitalier tertiaire.

Méthode

Entre 1997 et 2009, 107 patients ont bénéficié d’une procédure de Ross (âge moyen : 30±11 ans ; homme : 69 % ; 21 patients âgés de moins de 18 ans). Ces patients ont été suivis en échocardiographie et le diagnostic de sténose de l’homogreffe a été porté sur un gradient pic à pic>36mmHg ainsi que sur les résultats au décours de la réintervention.

Résultats

Après un suivi de 15 ans (médian : 11 ans), les données cliniques et échographiques étaient disponibles chez 91 (85 %), 104 (98 %) des patients respectivement. Vingt-six des 91 patients (29 %) ont développé une sténose de l’homogreffe et 10 patients (10 %) ont bénéficié d’une réintervention au cours de 13 procédures, puisque 3 patients ont dû avoir secondairement un remplacement chirurgical, 3 patients ayant bénéficié d’un remplacement pulmonaire percutané et un patient ayant nécessité l’implantation d’un stent. Les trois autres patients ont bénéficié de deux autres procédures lors du suivi ; un patient est décédé au décours d’un infarctus du myocarde lié à la procédure. Le taux de survie sans sténose de l’homogreffe ou réintervention à un an, 5 ans et 10 ans était de 96, 82 et 75 % et de 99, 94 et 91 %, respectivement. Les patients pédiatriques avaient une survie sans sténose pulmonaire moindre (hazard ratio : 3,50, IC 95 % : 1,56–7,90 ; p =0,002) bien qu’il n’y ait pas de différence significative en ce qui concerne le taux de réintervention (hazard ratio : 2,01, IC 95 % : 0,52–7,78 ; p =0,31). Un âge plus jeune du donneur de l’homogreffe était également un prédicteur de la sténose (hazard ratio : 0,97, IC 95 % : 0,94–0,99 ; p =0,046).

Conclusion

Les probabilités de sténose d’une homogreffe et d’une réintervention 10 ans après une procédure de Ross sont de respectivement 29 et 10 % ; seul un patient est décédé au décours d’une réintervention. Un âge plus jeune du donneur et du patient sont associés avec un taux accru de sténose.

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Keywords : Homograft, Aortic valve, Survival, Ross procedure

Mots clés : Homogreffe, Valve aortique, Survie, Procédure de Ross

Abbreviations : CI, HR


Background

The Ross procedure [1] is a therapeutic alternative in the treatment of selected groups of patients with aortic valve disease. At present, it is considered a particularly useful option in children and young adults because, besides providing haemodynamic advantages and acceptable durability, it has good adaptation to the growth of paediatric patients, and offers the possibility to avoid anticoagulation [2, 3]. The limited use of this procedure results, in part, from its greater technical complexity, but also because it has some long-term complications that require one or even several subsequent cardiac interventions.

Pulmonary graft stenosis is one of the complications that can appear in the long-term follow-up of patients after the Ross intervention. However, the factors involved in such degeneration and its clinical implications are not fully known. Knowing the possible triggers and clinical characteristics associated with a worse outcome would optimize patient selection, and help to prevent and treat complications arising in follow-up. So, our main objective was to describe the incidence and clinical impact of homograft stenosis, and to identify clinical, surgical and echocardiographic variables associated with this complication.

Methods
Study population

This prospective, observational, longitudinal study included all consecutive adult and paediatric (aged<18 years) patients who were operated on using the Ross procedure at our institution (a tertiary referral hospital), from the introduction of the technique in November 1997 until July 2009.

Surgical technique

All interventions were performed electively by only four cardiovascular surgeons, using cardiopulmonary bypass with standard bicaval and aortic cannulation. Early in the series, the patients were operated on under moderate hypothermia (five patients, at 28°C); subsequently, the procedures were performed under mild hypothermia (33°C). The integrity of the native pulmonary valve was evaluated in all cases by transverse pulmonary arteriotomy. After resection of the pathological aortic valve, the pulmonary autograft was implanted in the aortic position as a full aortic root replacement with interrupted sutures on an annulus of autologous pericardium, anastomosing the coronary buttons to the autograft with a running suture, and the autograft to the ascending aorta. In recent years, we supported the neosinotubular junction with 2 or 3cm of Dacron graft in all patients. The right ventricular outflow tract was restored with a pulmonary homograft implantation, with distal and proximal running polypropylene sutures. In all cases we used a pulmonary homograft cryopreserved in liquid nitrogen at –196°C, treated in the Sectorial Tissue Bank Institution, and following the usual standards set by the Spanish Association of Tissue Banks. Human leukocyte antigen (HLA) typing and ABO compatibility testing were not performed.

Echocardiographic baseline and follow-up studies

The baseline echocardiographic study was performed before surgery by transthoracic echocardiography. All cases were scanned at our centre using the Acuson Sequoia 256® (Siemens, Mountain View, CA, USA) and iE33® (Philips, Amsterdam, Netherlands) ultrasound systems. The measurements, taken after at least 5minutes of rest, and in the absence of other factors that might lead to overestimation of the flow rate, were interventricular septum, diastolic and systolic diameters and left ventricular posterior wall with M mode; left ventricular ejection fraction with the biplane Simpson's method; assessment of valvular structure and function with bidimensional and Doppler echocardiography, with calculation of maximum and mean gradients by means of the simplified Bernoulli equation, and evaluation of valvular regurgitation according to the recommendations of scientific societies [4, 5, 6, 7]; measurement of aortic and pulmonary annuli from the parasternal long axis and short axis, respectively, and evaluation of right ventricular size and function.

Clinical and echocardiographic data were collected at discharge, then at 6 and 12 months, and annually thereafter. Echocardiographic follow-up studies were performed according to an identical protocol to baseline echocardiography, with special attention to the study of the structure and function of the pulmonary autograft and pulmonary homograft. Both annuli were measured, and the maximum and mean transvalvular gradients were determined by the simplified Bernoulli equation. Valvular regurgitation was evaluated according to the recommendations of scientific societies [4, 5, 6, 7].

Definition of study endpoints

For this study, three main objectives were considered in the follow-up: the appearance of homograft stenosis; the need for homograft reintervention; and, finally, the study of possible predictors of these complications. We decided to analyse just the homograft stenosis because of the low rate and grade of insufficiency. We observed only 22 cases of homograft regurgitation in our series: none of them severe, five moderate (two with significant stenosis) and 17 mild, with no homograft reintervention for this indication. The outcome “homograft stenosis” was defined as a maximum transvalvular gradient of at least 36mmHg. This cut-off point was selected because it is the one considered in the guidelines as at least moderate stenosis and, therefore, requires closer clinical and echocardiographic follow-up. The “homograft reintervention” outcome included surgical replacement and percutaneous interventions (valvuloplasty, stenting or percutaneous implantation of pulmonary prosthesis). The criteria used to reoperate on patients were those recommended by clinical practice guidelines [8, 9], and included: symptomatic worsening; objective worsening of right ventricular function and/or progressive right ventricular dilatation; and medically intractable infective endocarditis or endocarditis with significant functional involvement of the homograft.

The appearance of autograft dysfunction, autograft reintervention and global mortality and its causes were also registered in the follow-up.

Statistical analysis

Statistical analyses were performed using SPSS 15 for Windows (SPSS Inc., Chicago, IL, USA). Continuous variables are expressed as mean±standard deviation (range). Categorical data are described using frequencies and percentages. Actuarial estimates of freedom from homograft stenosis, autograft dysfunction and reintervention were acquired using the Kaplan-Meier method. Possible determinants of clinical and echocardiographic outcomes were assessed by the Cox proportional hazards test, and for dichotomous qualitative variables we also used the log-rank test. We used multivariable Cox models for the study of possible predictors of homograft stenosis, initially including all variables with significance<0.10 in the univariate analysis, and removed the non-significant variables in successive backward steps to get variables independently associated with this outcome. The multivariable analysis was not performed for the reintervention endpoint because there were insufficient events. Statistical significance was set at P <0.05.

Results
Preoperative patient characteristics

From November 1997 to July 2009, a total of 107 Ross interventions were performed at our centre. Preoperative patient characteristics are presented in Table 1. Our sample consisted mainly of young men with normal left ventricular systolic function and severe aortic stenosis of congenital aetiology; 20% were paediatric patients.

Follow-up

After 15 years of follow-up (median: 11 years, interquartile range: 8–13 years) echocardiographic data were available in 91 patients (85%), and clinical data were available in 104 patients (98%); only two patients were lost to follow-up.

We observed three deaths in our series. We had an intraoperative death in a paediatric patient with a complex congenital heart disease (severe aortic stenosis and coarctation of aorta) in a critical preoperative situation. Another patient died after reoperation of the autograft because of a pseudoaneurysm. The third patient died after two percutaneous procedures for homograft stenosis. Overall survival was 97% at median follow-up.

A total of 21/104 (20%) patients required surgical or percutaneous reintervention in follow-up, 11 on the autograft (10%) and 10 on the homograft (10%). The rates of survival free from reintervention of both valve substitutes at 5 and 10 years were 88% and 81%, respectively.

The causes of autograft reintervention were: severe regurgitation secondary to autograft dilatation in seven patients; endocarditis of the autograft in three patients; and pseudoaneurysm of the autograft in one patient, who died after reoperation. Actuarial survival free from autograft reintervention was 95% at 5 years and 89% at 10 years.

A total of 26/91 (29%) patients developed at least moderate homograft stenosis. However, only 10/104 (10%) patients had to undergo one or even two reinterventions. The rate of freedom from at least moderate stenosis in our sample was 96% at 1 year, 82% at 5 years and 75% at 10 years (Figure 1A). The mean time to diagnosis of this complication was 50±48 months (median: 24 months, range: 4–148 months).



Figure 1


Figure 1. 

A. Freedom from at least moderate homograft stenosis in our series. B. Freedom from homograft reintervention in our series. C. Freedom from at least moderate homograft stenosis by age group. D. Freedom from homograft reintervention by age group.

Zoom

Freedom from homograft reintervention was 99%, 94% and 91% at 1, 5 and 10 years respectively (Figure 1B). The reasons for reoperation in our series were clinical worsening and/or systolic dysfunction or dilatation of the right ventricle (n =9), and medically intractable infective endocarditis on a previously stenosed homograft (n =1). The mean time to first reintervention on the homograft was 56±43 months (median: 33 months, range: 7–126 months).

In the group of patients who had to undergo reintervention, three were treated with surgical homograft replacement and four were treated percutaneously (three patients underwent a transcatheter pulmonary valve implantation, and a supravalvular stent was implanted in the pulmonary position in one patient). The other three remaining patients underwent two procedures each, one deferred over time: one patient received a supravalvular stent in pulmonary position and, 78 months later, a percutaneous pulmonary valve because of restenosis and clinical deterioration; in another patient, a transcatheter pulmonary valve was implanted initially, but 74 months later it had to be replaced surgically because of endocarditis and functional restenosis; finally, one patient underwent a pulmonary valvuloplasty, but 20 months later it was necessary to implant a percutaneous pulmonary valve because of restenosis. This last patient died during the procedure because of acute myocardial infarction after occlusion of the left main coronary artery. The remaining patients continue alive, in functional class I, and none has been reoperated on again.

In the univariate risk analysis, younger age of the recipient (expressed as a continuous and dichotomous form, paediatric group yes/no) and younger age of the allograft donor were significantly associated with the development of at least moderate homograft stenosis. History of previous cardiac surgery showed a trend towards association, but did not reach statistical significance. Recipient and donor sex, homograft size, freezing time, congenital aetiology and the use of blood products during the perioperative period were not significantly associated with this event (Table 2).

However, in the multivariable risk analysis of potential predictors of homograft stenosis, only belonging to the paediatric group showed a statistically significant association after adjusting for donor age and previous cardiac surgery (hazard ratio [HR]: 3.17, 95% confidence interval [CI]: 1.22–8.20; P =0.02). At median follow-up, freedom from homograft stenosis in the paediatric group was 42% versus 79% in the adult group (P =0.005; Figure 1C).

In the univariate risk analysis of potential predictors of reintervention, the paediatric group had a numerically higher rate of this event compared with the adult group (17% vs. 8%). However, this association was not statistically significant (HR: 2.01, 95% CI: 0.52–7.78; P =0.31) (Figure 1D). We found no significant association of this event with recipient or donor age, previous cardiac surgery, donor or recipient sex, homograft size, time of freezing, congenital aetiology or the use of blood products in the perioperative period (Table 3).

Discussion

In this study, the proportion of patients who developed at least moderate homograft stenosis was not negligible (29%). Although only 10% of patients had to undergo further invasive therapies on the homograft, these may be not definitive, and none of them is free from complications. Recipient age stands out among the possible predictors of homograft stenosis, so the risk of developing this event in a paediatric group is three times higher. Nevertheless, in our experience, the paediatric group did not have a significantly higher risk of reintervention.

The survival rates free of homograft stenosis published to date support our findings [10, 11]. However, other studies, such as that of Mokhles et al. [12], have observed higher survival rates. In this German registry, with a larger sample size (n =1624), freedom from homograft dysfunction at 1, 10 and 15 years was 98.4%, 88.4% and 78.1% respectively. The differences found in the literature may be justified on several counts. First, the definition of homograft dysfunction differs depending on the series; Mokhles et al. included patients with homograft stenosis, but also those with regurgitation>grade 2 or patients who required reoperation, so the results are not exactly comparable. Moreover, the mean echocardiographic follow-up was shorter than ours (mean: 5.5±4.8 years), and it is possible that some of these patients develop this event as their follow-up is prolonged. The age of the patients included in this series is another factor that may have influenced the results. All patients included in this registry were aged>16 years, with an older mean age than in our study (43.7±12 years), so the number of paediatric patients included in the follow-up (who, according to our findings, presented earlier homograft dysfunction) was also lower.

Currently, there are few data on the mean time when stenosis or clinically significant homograft dysfunction emerges. In our sample, and in accordance with previous studies [10, 12], half of the patients developed homograft stenosis in the first 2 years after the Ross operation (mean 50±48 months, median 24 months). However, the wide range observed for this event may be justified, not only by the age spectrum comprising our sample, but also by less well studied factors, such as inflammatory or immune response [13, 14]. In this context, close clinical and echocardiographic follow-up of these patients continues to be of great importance.

Some patients who develop at least moderate homograft stenosis have to undergo reintervention on this valve substitute (10% of the total in our series). This proportion of patients is similar to findings in other studies [15]. However, reoperation-free survival rates reported by other groups were superior to ours. After a mean 11.4 years of follow-up in the study by Kalfa et al. [16], reoperation-free survival rates were 95.7% and 90.8% at 10 and 15 years, respectively; however, this analysis only included surgical reinterventions. Likewise, a study published by David et al. [17] had a reoperation-free survival rate of 95.5% after 15 years of follow-up, although they mentioned in their discussion that 17 patients in their series are currently presenting echocardiographic signs of valvular dysfunction (defined as peak gradient>40mmHg and/or moderate or severe regurgitation), and are being closely monitored to determine the time of reoperation.

Although, increasingly, there are more studies on decellularized homografts, and some authors advocate a higher reoperation-free survival with this type of homograft compared with the conventional type [11, 18], in our centre, because the evidence available to date is not yet conclusive, we continue to use cryopreserved homografts.

The time between the Ross operation and the first homograft reintervention is extremely variable. Unlike the data obtained by other series, in which reintervention occurred later [19], in our sample the mean time was 56±43 months, with a wide range (between 7 and 126 months). In any case, we have to keep in mind that the definition of reintervention may refer to surgical and percutaneous procedures (as in our case), or may only consider explantation of degenerate homograft, as in the study by Juthier et al. [20]. Nowadays, the possibility of using percutaneous treatment with satisfactory short-to-medium term results may delay surgical explantation of the homograft until paediatric patients have reached adulthood or until women of childbearing age have had offspring. The impact on right ventricular function associated with this delay has yet to be analysed.

Among the possible predictors of at least moderate homograft stenosis, belonging only to the paediatric group showed statistically significant association in our series, after adjusting for donor age and previous cardiac surgery. This association, already observed in other studies [12, 21, 22, 23], is supported by the study of Mokhles et al. [15]. This group found that freedom from homograft reoperation was lower in paediatric patients, but they also found that patients had an increasing rate of survival free of reintervention as long as the age increased at the time of the Ross operation (freedom from homograft reoperation at 10 years: 86% in patients aged<18 years; 87% for those aged between 18 and 30 years; and 98% in patients aged>30 years at the time of Ross procedure). Equally, other groups, such as Hörer et al. [24] (who studied a German registry composed exclusively of patients undergoing the Ross procedure before the aged of 16 years, with a mean age at surgery of 10.1 years), Luciani et al. [19] (who studied an Italian paediatric Ross registry with a mean age at surgery of 9.4 years and a median follow-up of 8.7 years) and Kallio et al. [25] (who conducted a retrospective study of patients with a mean age at surgery of 4.8 years and a median follow-up of 11.5 years), have described rates of freedom from reoperation that are lower than those observed in other studies, in which adult patients were included (79.6%, 86% and 83% at 10 years, respectively).

However, it is noteworthy that the study by Hörer et al. [24] also included patients with complex congenital heart disease (19.1%), in whom, like in other studies [26], earlier homograft failure rates were reported (especially in those implanted in the heterotopic position), and the reconstruction of the outflow tract of the right ventricle was performed not only with pulmonary cryopreserved homografts, as in our case, but also with aortic homografts, which these authors have described as having an increased risk of homograft stenosis.

History of cardiac surgery showed (in univariate analysis) a trend towards association with homograft stenosis outcome, but this did not reach statistical significance (HR: 2.17, 95% CI: 0.95–4.96; P =0.07). One possible explanation is that this trend could be influenced by the presence of complex underlying congenital heart disease and, therefore, be associated with a younger age at the time of the Ross operation, and with haemodynamic factors that may worsen the longevity of the homograft. Like other groups [10, 12], the sex of the recipient, the sex of the donor and the freezing time did not show an association with homograft stenosis. Unlike in other series [24], congenital aetiology itself did not show any association with homograft stenosis. In any case, it is noteworthy that our sample consisted mainly of patients with isolated aortic valve disease, and there were just a few patients with complex congenital heart disease.

In the same way, we did not observe an association between the size of the homograft and evolution towards stenosis. A study published by Kalfa et al. [27] identified a homograft diameter of<22mm as a possible predictor of this event. In our series, which systematically implanted slightly oversized homografts with respect to the recipient, there was only one patient with a homograft diameter of<22mm, so we had insufficient data to compare these findings.

In a previous study published by our group [28], with a sample of 76 patients and a mean follow-up of 27±15.1 months, we reported that the use of blood products in the perioperative period was higher in the group with pulmonary stenosis compared with in the control group. Nevertheless, in this study, the use of blood products did not show a statistically significant association with outcome, except the postoperative use of plasma. In the current study, with a longer follow-up and a larger sample size, we did not find any association between the use of blood products and homograft stenosis in follow-up.

Unlike the results reported by other groups [21, 22, 23, 29], belonging to the paediatric group did not show a statistically significant association as a potential predictor of reintervention on the pulmonary homograft. It is noteworthy that these findings could be affected by the small number of events observed in our study. Also, in line with other studies [15], we did not find a statistical association with recipient or donor age, previous cardiac surgery, donor or recipient sex, homograft size, time of freezing, congenital aetiology or the use of blood products. The multivariable analysis was not performed for reintervention outcome because there were insufficient events.

The partial or complete support of the autograft root with synthetic materials has been proposed as a good option for preventing autograft dilatation [30, 31]. Despite the potential long-term benefits, we exercise caution with this approach, because it can extend the time of ischaemia and interfere with proper homeostasis. The inclusion technique could also cause leaflet prolapse or ascending aorta dilatation, and require a more demanding surgical reoperation technique. Moreover, some series have not found any significant improvement in the rate of long-term autograft failure [29, 32]. In the last few years, we decided (in addition to supporting the aortic root annulus with autologous pericardium) to support the neosinotubular junction with 2 or 3cm of Dacron graft. This modification could, in theory, prevent aortic dilatation at this level with a very small portion of prosthetic material, and respecting the valve geometry, with an acceptable ischaemia time and long-term results.

In recent years, we have acquired greater insight into Ross procedure and its long-term complications. Moreover, we have information about short- and long-term results in other surgical alternatives to this procedure and their complications [33, 34]. With this experience, we should be able to improve patient selection and optimize the approach to aortic diseases. Despite paediatric patients having a greater rate of valvular dysfunction and reintervention, we continue to consider that the Ross procedure is a good option in this population, especially given that other surgical options have important rates of reintervention and greater anticoagulation-related events [33, 34]. In older patients, we used the Ross technique if there were many anticoagulation-related risk factors or because of patient preference. In our opinion, the optimal recipient is a young patient or a woman of childbearing age, with isolated aortic stenosis, preferably non-rheumatic aetiology, and without previous cardiac surgery [35]. Therefore, we recommend taking this approach in these types of patients, and whenever the referral centre has enough experience.

Study limitations

Despite having a clinical and echocardiographic follow-up of>10 years, this was an observational study from a single centre. The sample size and, hence, the statistical power were more limited than other contemporary series. In addition, the low incidence of events, especially regarding reintervention, prevented us from drawing definitive conclusions regarding the analysis of potential predictors of stenosis or reintervention.

Conclusions

In this study, the probabilities of homograft stenosis and reintervention, 10 years after the Ross procedure, were 26% and 10% respectively, and only one patient had a reintervention-related death. Younger donor and recipient age were associated with a higher rate of stenosis. Clinical and echocardiographic follow-up should be particularly close in those patients who undergo the Ross procedure at an early age, in order to make an early diagnosis of this complication.

Disclosure of interest

The authors declare that they have no competing interest.

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