The Landscape of Congenital Heart Disease Treated with the Ross Procedure.

OBJECTIVES: The Ross procedure has excellent outcomes in the pediatric population. Some series report age and anatomy dependent outcomes, but no comprehensive analysis stratified by these variables exists. We sought to describe the landscape of congenital heart disease (CHD) treated with the Ross procedure and identify the patients best served with this operation. METHODS: Over 30 years, 317 pediatric patients underwent the Ross procedure. Patients were stratified into 4 age groups: neonates (<31days,n=21), infants (31days-1year,n=40), children (1-12years,n=165), and adolescents (13-18years,n=91), and 3 anatomical groups: isolated aortic valve (AV) disease (n=221), Shone's complex or multilevel LVOT obstruction (n=61), and complex CHD (n=35). Groups were compared across outcomes. RESULTS: Neonates and infants had the highest rates of Shone's syndrome (p<0.001), complex CHD (p<0.001), concomitant root enlargement (p<0.001), and arch procedures (p<0.001). Operative mortality and morbidity were 14/317 (4.4%) and 44/317 (14%) respectively. Both were higher in neonates and infants (p<0.001,p<0.001), but lower for patients with isolated AV disease (p<0.001,p<0.001). 10-year survival and freedom from LVOT reintervention were 92% and 81% and were both significantly better in patients with isolated AV disease compared to those with complex CHD (p<0.001,p=0.005). In neonates and infants with isolated AV disease, operative mortality was 1/23 (4%), morbidity was 2/23 (9%), 10-year survival was 85.6%, and 10-year freedom from LVOT reintervention was 88.4%. CONCLUSIONS: Among pediatric patients, those with isolated AV disease are best served with the Ross procedure, regardless of age. Complex CHD is associated with lower survival and increased risk of LVOT reintervention.

Computational analysis of heart valve growth and remodeling after the Ross procedure.

During the Ross procedure, an aortic heart valve is replaced by a patient's own pulmonary valve. The pulmonary autograft subsequently undergoes substantial growth and remodeling (G&R) due to its exposure to increased hemodynamic loads. In this study, we developed a homogenized constrained mixture model to understand the observed adaptation of the autograft leaflets in response to the changed hemodynamic environment. This model was based on the hypothesis that tissue G&R aims to preserve mechanical homeostasis for each tissue constituent. To model the Ross procedure, we simulated the exposure of a pulmonary valve to aortic pressure conditions and the subsequent G&R of the valve. Specifically, we investigated the effects of assuming either stress- or stretch-based mechanical homeostasis, the use of blood pressure control, and the effect of root dilation. With this model, we could explain different observations from published clinical studies, such as the increase in thickness, change in collagen organization, and change in tissue composition. In addition, we found that G&R based on stress-based homeostasis could better capture the observed changes in tissue composition than G&R based on stretch-based homeostasis, and that root dilation or blood pressure control can result in more leaflet elongation. Finally, our model demonstrated that successful adaptation can only occur when the mechanically induced tissue deposition is sufficiently larger than tissue degradation, such that leaflet thickening overrules leaflet dilation. In conclusion, our findings demonstrated that G&R based on mechanical homeostasis can capture the observed heart valve adaptation after the Ross procedure. Finally, this study presents a novel homogenized mixture model that can be used to investigate other cases of heart valve G&R as well.

Long-term results of patients undergoing the Ross procedure after a previous aortic valve surgery.

OBJECTIVES: To assess the long-term outcomes of patients undergoing a Ross procedure in the context of a redo aortic valve (AV) surgery. METHODS: Prospectively collected data in all consecutive adults who underwent a Ross procedure were analyzed to compare the Ross procedure performed as a first surgery (RF) or as a redo surgery (RP). RESULTS: Between 1990 and 2021, 395 Ross procedures were performed at our center (RF, n = 345; RP, n = 50). A 2:1 propensity score matching was performed (RF, n = 100; RP, n = 50). The overall median follow-up was 11.6 years (interquartile range, 5.0-21.8 years) and 100% complete. Mean survival at 20 years was 87 ± 12% in the RF group and 87 ± 8% in the RP group (P = .30). The cumulative incidence of autograft reintervention at 10 years and 20 years was 6 ± 3% and 21 ± 6%, respectively, in the RF group and 9 ± 5% and 25 ± 8%, respectively, in the RP group (P = .74). The AV gradient remained stable up to 20 years in both groups (P = .42). The size of the sinuses of Valsalva tended to increase over time in the RF group but remained stable in the RP group (P = .03). CONCLUSIONS: The ross procedure after a previous sternotomy for AV surgery is safe and offers good long-term results. Patients undergoing redo AV intervention have similar results as patients undergoing a primary Ross procedure, perhaps with a lower risk of autograft dilatation.

Long-term outcome after the Ross procedure in 173 adults with up to 25 years of follow-up.

OBJECTIVES: The potential risk of autograft dilatation and homograft stenosis after the Ross procedure mandates lifelong follow-up. This retrospective cohort study aimed to determine long-term outcome of the Ross procedure, investigating autograft and homograft failure patterns leading to reintervention. METHODS: All adults who underwent the Ross procedure between 1991 and 2018 at the University Hospitals Leuven were included, with follow-up data collected retrospectively. Autograft implantation was performed using the full root replacement technique. The primary end-point was long-term survival. Secondary end-points were survival free from any reintervention, autograft or homograft reintervention-free survival, and evolution of autograft diameter, homograft gradient and aortic regurgitation grade over time. RESULTS: A total of 173 adult patients (66% male) with a median age of 32 years (range 18-58 years) were included. External support at both the annulus and sinotubular junction was used in 38.7% (67/173). Median follow-up duration was 11.1 years (IQR, 6.4-15.9; 2065 patient-years) with 95% follow-up completeness. There was one (0.6%) perioperative death. Kaplan-Meier estimate for 15-year survival was 91.1% and Ross-related reintervention-free survival was 75.7% (autograft: 83.5%, homograft: 85%). Regression analyses demonstrated progressive neoaortic root dilatation (0.56 mm/year) and increase in homograft gradient (0.72 mmHg/year). CONCLUSIONS: The Ross procedure has the potential to offer excellent long-term survival and reintervention-free survival. These long-term data further confirm that the Ross procedure is a suitable option in young adults with aortic valve disease which should be considered on an individual basis.

Cell signaling and tissue remodeling in the pulmonary autograft after the Ross procedure: A computational study.

In the Ross procedure, a patient's pulmonary valve is transplanted in the aortic position. Despite advantages of this surgery, reoperation is still needed in many cases due to excessive dilatation of the pulmonary autograft. To further understand the failure mechanisms, we propose a multiscale model predicting adaptive processes in the autograft at the cell and tissue scale. The cell-scale model consists of a network model, that includes important signaling pathways and relations between relevant transcription factors and their target genes. The resulting gene activity leads to changes in the mechanical properties of the tissue, modeled as a constrained mixture of collagen, elastin and smooth muscle. The multiscale model is calibrated with findings from experiments in which seven sheep underwent the Ross procedure. The model is then validated against a different set of sheep experiments, for which a qualitative agreement between model and experiment is found. Model outcomes at the cell scale, including the activity of genes and transcription factors, also match experimentally obtained transcriptomics data.

Valve-sparing double root replacement after the Ross procedure.

An inherent limitation of the Ross procedure is long-term two valve disease which will require repetitive reintervention. In this case, a 31-year-old man who had underwent Ross operation due to congenital bicuspid valve 20 years before, underwent double root replacement: valve sparing root reimplantation concomitant with the right ventricular outflow tract (RVOT) reconstruction with a bioprosthesis for severe RVOT stenosis. Although the diameter of autograft root was 42 mm and aortic insufficiency was mild, we added root surgery due to concerns regarding autograft root dilation in response to left ventricular volume load after RVOT reconstruction. The postoperative echocardiogram showed minimal aortic valve regurgitation and normal blood flow in the RVOT, and he was discharged from the hospital on the 17th day after the surgery. In this report, we present the outcomes of Valve-sparing double root replacement following Ross surgery.

Autograft Reoperation Following the Ross Procedure: Evolving Strategies and Future Perspectives.

Background: Pulmonary autograft failure remains a cause of reoperation following the Ross procedure. The aim of this study is to describe our evolving approach to autograft reoperations. Methods: Retrospective study of all patients who underwent a pulmonary autograft reoperation following a Ross procedure between June 1997 and July 2022. Results: Two-hundred and thirty-five Ross procedures were performed. Thirty-six patients (15%) plus one referral underwent an autograft reoperation at a median of 7.8 years (IQR 4.6-13.6). The main indication was: neoaortic root dilatation associated with mild/moderate (n = 12) or severe (n = 8) aortic regurgitation; isolated severe aortic regurgitation (n = 6); infective endocarditis (IE) (n = 8); and aortic root pseudoaneurysm with no history of IE (n = 3). The autograft was spared in 29 cases (78%): 9 patients (24%) underwent aortic valve repair or aortic root remodeling, 15 patients (40%) aortic root reimplantation, 5 patients neoaortic root stabilization with a Personalized External Aortic Root Support (PEARS) sleeve. There were no in-hospital deaths. At a median follow up of 37 months (IQR 8-105), all patients were alive, 30 (81%) were asymptomatic. Eight patients (22%) required nine further reoperations. Estimated freedom from further reoperation was 90%, 72%, and 72% at 12-, 36-, and 60-months. Conclusions: Autograft reoperations following the Ross procedure can be safely performed and do not affect overall survival in the early and mid-term. Valve-sparing autograft replacement is technically feasible but remains at risk of further interventions. Alternative strategies, such as the PEARS sleeve, are becoming increasingly available but requires validation in the long term.

Letter to the Editor Ross procedure valve function, clinical outcomes and predictors after 25 years follow up.

The following letter presents an answer of a comment of our work titled "Ross procedure: valve function, clinical outcomes and predictors after 25 years' follow-up," recently published in your journal by Rangwala et al.1 As our colleagues point out, the Ross procedure has excellent survival rates but a significant risk of valve dysfunction and therefore reintervention at follow-up. Although the survival advantage with the Ross procedure appears to be consistent compared with mechanical valve substitutes, this benefit is not as clear compared with biological valve substitutes. However, biological valve substitutes also have significant reintervention rates during follow-up. The different surgical modifications of the Ross procedure have not clearly demonstrated better results in follow-up in terms of autograft reintervention. This procedure can be performed in a medium-volume center with good results as long as adequate patient selection and adequate surgical training are carried out.

Ex vivo evaluation of 3 different right ventricular outflow tract substitutes.

OBJECTIVES: The Ross procedure represents an excellent treatment option in younger patients with aortic stenosis but is limited by poor availability of homografts. In this study, we investigated the hydrodynamic performance of 3 different types of right ventricular outflow tract replacement with pericardium or synthetic material. METHODS: Three different types of valved conduits were constructed using pericardium and/or synthetic material (Group PEPE: pericardial cusps and pericardial conduit, Group PEPR: pericardial cusps and Dacron conduit, Group PRPR: expanded polytetrafluoroethylene cusps and Dacron conduit). The conduits were designed according to the Ozaki method. Their hydrodynamic performance (effective orifice area, mean pressure gradient and leakage volume) were evaluated in a mock circulation loop at different hydrodynamic conditions. RESULTS: Hydrodynamic assessment showed significantly larger effective orifice area of PEPE and PEPR compared to PRPR under all conditions and there were no significant differences between PEPE and PEPR [for condition 2: PEPE 2.43 (2.35-2.54) cm2, PEPR: 2.42 (2.4-2.5) cm2, PRPR: 2.08 (1.97-2.21) cm2, adjusted pairwise comparisons: PEPE versus PEPR: P = 0.80, PEPE versus PRPR: P < 0.001, PEPR versus PRPR: P < 0.001]. Mean pressure gradient was significantly lower for PEPE and PEPR compared with PRPR, whereas no significant differences were seen between PEPE and PEPR. Leakage volume was significantly lower for PEPE and PEPR compared with PRPR under all conditions while leakage was similar between PEPE and PEPR. CONCLUSIONS: Pulmonary graft reconstruction with pericardium cusps showed superior hydrodynamic performance compared with polytetrafluoroethylene cusps. Our results suggest that it could be considered as an alternative substitute for right ventricular outflow tract replacement during the Ross procedure.

Technical considerations and sizing of external annuloplasty in the Ross procedure.

Pure aortic regurgitation and dilation of aortic annulus are the most significant risk factors for the failure of pulmonary autograft after the Ross procedure. Aortic annuloplasty has a positive effect on the durability of the autograft. Previously, we described a technique for external annuloplasty with dedicated CORONEO ring. In the present manuscript, we suggest the sizing of annuloplasty based on the diameter of pulmonary autograft annulus.

Surgical Heritage: You Had to Be There, Ross: The Comeback Kid.

Half a century after the first pulmonary autograft operation (Ross operation), performed in 1967 by Donald Ross in central London, there is a very strong conviction that the Ross operation is the best available valve substitute today, not only for children, but also for younger and older adults. The Ross operation has stimulated a lot of science to do with tissue-engineering and biology of heart valves, which is a promising avenue for the future. For one of us (M.Y.), it has certainly been a privilege to be associated with the comeback of the Ross operation.

Late Pulmonary Autograft Dilation: Can We Make a Good Operation Great? The Tailored Approach.

While it is the main viable option in the growing child and young adult, the Ross procedure has expanded its applicability to older patients, for whom long-term results are equivalent, if not superior, to prosthetic aortic valve replacement. Strategies aiming at mitigating long-term autograft failure from root enlargement and valve regurgitation have led some to advocate for root reinforcement with prosthetic graft material. On the contrary, we will discuss herein the rationale for a tailored approach to the Ross procedure; this strategy is aimed at maintaining the natural physiology and interplay between the various autograft components. Several technical maneuvers, including careful matching of aortic and autograft annuli and sino-tubular junction as well as external support by autologous aortic tissue maintain these physiologic relationships and the viability of the autograft, and could translate in a lower need for late reintervention because of dilation and/or valve regurgitation.

Late Pulmonary Autograft Dilation: Can We Make a Good Operation Great? The Supported Ross.

The Ross procedure is an excellent option for aortic valve replacement resulting in outstanding hemodynamic performance and the ability to avoid systemic anticoagulation. The long-term durability of the autograft is generally good but concerns for later aortic root dilation with ensuing neoaortic insufficiency have prompted efforts to stabilize the autograft, root, sinuses and Sino-tubular junction in order to delay or entirely avoid late reinterventions on the neoaortic root. We have employed an inclusion technique, supporting the Auto-graft in a Terumo Gelweave™ Valsalva graft. We performed a retrospective study of all 129 patients undergoing the Ross procedure from 1992 to 2019 at Children's Wisconsin. Fifty-one underwent the supported Ross (SR) and 78 underwent unsupported Ross (UR). Structured clinical data was collected and echocardiograms were reviewed. Median follow-up was 4.9 years (up to 22.6 years) for UR patients and 3.6 years (up to 11.4 years) for SR patients. In order to provide a fair comparison, we sub -analyzed patients aged 10 to 18 years who underwent the Ross procedure, 16 who underwent the UR and 18 patients who underwent the SR. Change in aortic annulus diameter (P = 0.002), aortic sinus diameter (P = 0.001) change in left ventricular function (P = 0.039) and change in aortic insufficiency (P = 0.008) were all worse in UR. The SR is simple, reproducible, and predictable. It seems to prevent change in annulus diameter, sinus diameter and to reduce late neoaortic insufficiency. Longer follow-up with a larger group of patients is required to draw definitive conclusions.

Ross procedure or mechanical aortic valve, which is the best lifetime option for an 18-year-old? A decision analysis.

Objectives: Identifying the optimal solution for young adults requiring aortic valve replacement (AVR) is challenging, given the variety of options and their lifetime complication risks, impacts on quality of life, and costs. Decision analytic techniques make comparisons incorporating these measures. We evaluated lifetime valve-related outcomes of mechanical aortic valve replacement (mAVR) versus the Ross procedure (Ross) using decision tree microsimulations modeling. Methods: Transition probabilities, utilities, and costs derived from published reports were entered into a Markov model decision tree to explore progression between health states for hypothetical 18-year-old patients. In total, 20,000 Monte Carlo microsimulations were performed to model mortality, quality-adjusted-life-years (QALYs), and health care costs. The incremental cost-effectiveness ratio (ICER) was calculated. Sensitivity analyses was performed to identify transition probabilities at which the preferred strategy switched from baseline. Results: From modeling, average 20-year mortality was 16.3% and 23.2% for Ross and mAVR, respectively. Average 20-year freedom from stroke and major bleeding was 98.6% and 94.6% for Ross, and 90.0% and 82.2% for mAVR, respectively. Average individual lifetime (60 postoperative years) utility (28.3 vs 23.5 QALYs) and cost ($54,233 vs $507,240) favored Ross over mAVR. The average ICER demonstrated that each QALY would cost $95,345 more for mAVR. Sensitivity analysis revealed late annual probabilities of autograft/left ventricular outflow tract disease and homograft/right ventricular outflow tract disease after Ross, and late death after mAVR, to be important ICER determinants. Conclusions: Our modeling suggests that Ross is preferred to mAVR, with superior freedom from valve-related morbidity and mortality, and improved cost-utility for young adults requiring aortic valve surgery.

The Ross Procedure in a Case of Baraitser-Winter Syndrome: A Case Report.

Baraitser-Winter syndrome (BRWS) is a rare genetic disorder caused by mutations in the ACTB and ACTG1 genes. It is characterized by intellectual disability, physical malformations, and dysmorphic craniofacial features. Additionally, cardiovascular abnormalities may also be present. We present a case of a 15-year-old boy with BRWS associated with congenital bicuspid aortic valve and severe aortic insufficiency which was managed successfully with Ross procedure.

Letter to the Editor: Ross procedure: Valve function, clinical outcomes and predictors after 25 years' follow-up.

The following letter presents a critique of the study titled "Ross procedure: valve function, clinical outcomes and predictors after 25 years' follow-up," recently published in your esteemed journal. This study provides a comprehensive analysis of the long-term outcomes of the Ross procedure, focusing on survival rates and incidence of valve dysfunction over a 25-year period. Despite revealing excellent overall survival rates and promising outcomes in pediatric patients, concerns regarding valvular failure and reintervention are underscored. While acknowledging limitations, such as sample size and observational biases, this study highlights the significance of surgeon experience in mitigating adverse outcomes. This critique emphasizes the study's contribution to understanding the efficacy and challenges of the Ross procedure, advocating further research to optimize patient outcomes.

Aortic insufficiency following balloon aortic valvuloplasty does not impact long-term autograft durability after the Ross procedure.

OBJECTIVE: Preoperative aortic insufficiency (AI) is associated with inferior autograft durability after the Ross procedure. However, many patients with aortic stenosis (AS) undergo balloon aortic valvuloplasty (BAV) early and present with longstanding AI before Ross. We studied how BAV and subsequent valvular pathology impacts autograft durability. METHODS: Patients undergoing the Ross operation from 1993 to 2020 were identified. Those who underwent BAV before Ross were compared with patients who did not undergo BAV and underwent Ross for predominant AI (AI group) or AS (AS group). Those who underwent previous open surgical aortic valve intervention were excluded. Primary outcome of interest was autograft failure, defined as a composite of autograft reintervention or severe insufficiency. RESULTS: A total of 198 patients were included. Seventy-nine (39.9%) underwent BAV and subsequently underwent the Ross for predominant AI (45.6%) or AS (54.4%). Of patients who did not undergo BAV, 66 (33.3%) presented with predominant AI and 53 (26.8%) with AS. Freedom from autograft failure at 15 years was 90%, 92%, and 62% in BAV, AS, and AI groups, respectively. The AI group was at significantly increased risk of long-term autograft failure (hazard ratio, 5.6; P = .01), whereas the AS and BAV groups had similar, low risk (hazard ratio, 1.1; P = .91). Autograft durability was similar among patients who received BAV and presented with AS or AI before the Ross (P = .84). CONCLUSIONS: BAV before the Ross procedure is common in patients with AS. These patients have excellent long-term autograft durability regardless of preoperative valvular pathology and should strongly be considered for the Ross operation.

The Ross Procedure: Imaging, Outcomes and Future Directions in Aortic Valve Replacement.

The Ross procedure is gaining recognition as a significant option for aortic valve replacement (AVR), and is particularly beneficial in specific patient groups. Although categorized as a class IIb recommendation in the 2020 American College of Cardiology (ACC)/American Heart Association (AHA), and the European Society of Cardiology (ESC) management guidelines on valvular heart disease, recent studies bolster its credibility. Research, including a propensity-matched study, underlines the Ross procedure's association with enhanced long-term survival and reduced adverse valve-related events compared to other AVR types. This positions the Ross procedure as a primary option for AVR in young and middle-aged adults within specialized centers, and potentially the only choice for children and infants requiring AVR. This review meticulously examines the Ross procedure, covering historical perspectives, surgical techniques, imaging, and outcomes, including hemodynamic performance and quality of life, especially focusing on pediatric and young adult patients. It explores contemporary techniques and innovations like minimally invasive approaches and tissue engineering, underscoring ongoing research and future directions. A summarization of comparative studies and meta-analyses reiterates the Ross procedure's superior long-term outcomes, valve durability, and preservation of the left ventricular function, accentuating the crucial role of patient selection and risk stratification, and pinpointing areas for future research.

Ross procedure: valve function, clinical outcomes and predictors after 25 years' follow-up.

OBJECTIVE: To describe long-term outcomes of the Ross procedure in a single center and retrospective series after 25 years follow-up. METHODS: From 1997-2019 we included all consecutive patients who underwent Ross procedure at our center. Clinical and echocardiographic evaluations were performed at least yearly. Echocardiographic valvular impairment was defined as at least moderate autograft or homograft dysfunction. Reintervention outcomes included surgical and percutaneous approach. RESULTS: 151 Ross procedures were performed (mean age 28±12years, 21 %<16years, 70 %male). After 25 years follow-up (median 18 years, interquartile range 9-21, only 3 patients lost) 12 patients died (8 %); Autograft, homograft or any valve dysfunction were present in 38(26 %), 48(32 %) and 75(51 %), respectively; and reintervention in 22(15%), 17(11%) and 38(26 %) respectively. At 20 years of follow-up, probabilities of survival free from autograft, homograft or any valve dysfunction were 63 %, 60 % and 35 %; and from reintervention, 80 %, 85 % and 67 %, respectively. The learning curve period (first 12 cases) was independently associated to autograft dysfunction (HR 2.78, 95 %CI:1.18-6.53, p = 0.02) and reintervention (HR 3.76, 95 %CI: 1.46-9.70, p = 0.006). Larger native pulmonary diameter was also an independent predictor of autograft reintervention (HR 1.22, 95 %CI:1.03-1.45, p = 0.03). Homograft dysfunction was associated with younger age (HR 5.35, 95 %CI: 2.13-13.47, p<0.001) and homograft reintervention, with higher left ventricle ejection fraction (HR 1,10, 95 %CI:1.02-1.19, p<0.02). CONCLUSIONS: In this 25 years' experience after the Ross procedure, global survival was high, although autograft and homograft dysfunction and reintervention rates were not negligible. Clinical and echocardiographic variables can identify patients with higher risk of events in follow up.

Influence of preoperative aortic regurgitation on long-term autograft durability and dilatation in children and adolescents undergoing the Ross procedure.

OBJECTIVE: Primary aortic insufficiency (AI) is a risk factor for autograft reintervention in adults undergoing the Ross procedure. We sought to examine the influence of preoperative AI on autograft durability in children and adolescents. METHODS: From 1993 to 2020, 125 consecutive patients between ages 1 and 18 underwent a Ross procedure. The autograft was implanted using a full-root technique in 123 (98.4%) and included in a polyethelene terephthalate graft in 2 (1.6%). Patients with aortic stenosis (aortic stenosis group) (n = 85) were retrospectively compared with those with AI or mixed disease (AI group) (n = 40). Median length of follow-up was 8.2 years (interquartile range, 3.3-15.4 years). The primary end point was the incidence of severe AI or autograft reintervention. Secondary end points included changes in autograft dimensions analyzed using mixed-effect models. RESULTS: The incidence of severe AI or autograft reintervention was 39.0% ± 13.0% in the AI group and 8.8% ± 4.4% in the aortic stenosis group at 15 years (P = .02). Annulus z scores increased in both aortic stenosis and AI groups over time (P < .001). However, the annulus dilated at a faster rate in the AI group (absolute difference, 3.8 ± 2.0 vs 2.5 ± 1.7; P = .03). Sinus of Valsalva z scores increased in both groups as well (P < .001), but at similar rates over time (P = .11). CONCLUSIONS: Children and adolescents with AI undergoing the Ross procedure have higher rates of autograft failure. Patients with preoperative AI have more pronounced dilatation at the annulus. Akin to adults, a surgical aortic annulus stabilization technique that modulates growth is needed in children.