Semilunar valve growth and function 10 years after infant heart transplantation: Predicting long-term outcomes of partial heart transplants.

INTRODUCTION: Partial heart transplants are a new type of pediatric transplant that replace defective heart valves with the parts of matched donor hearts containing the necessary valves. Short-term outcomes of partial heart transplants are excellent, but long-term outcomes are unknown. In order to predict the long-term outcomes of partial heart transplants, we evaluated long-term growth and function of semilunar heart valves transplanted in infancy as part of a heart transplant. METHODS: All children who underwent infant heart transplantation at a single center from 1997 to 2014 were included in this study. Children in whom echocardiograms after heart transplantation and after 10 years were not available for review were excluded. The echocardiograms were reviewed by two authors to analyze semilunar valve annulus diameters, Z-scores, peak valve gradients, and valve regurgitation. Statistical difference was determined using two-tailed, paired sample t-tests with Bonferroni correction for multiple comparisons. RESULTS: Data from 15 patients were analyzed. The aortic valve annulus averaged 1.3 cm (range 0.7-1.8 cm) immediately after transplantation and grew to an average of 1.7 cm (range 1.4-2.3 cm) after 10 years (p < .001). After 10 years, the aortic valve peak gradient avereraged 5.1 mmHg (range 2.1-15.5 mmHg) and none of the valves had more than trivial regurgitation. The pulmonary valve annulus averaged 1.5 cm (range 1.1-2.5 cm) immediately after transplantation and grew to an average of 2.1 cm (range 1.0-2.9 cm) after 10 years (p < .001). After 10 years, the pulmonary valve peak gradient averaged 4.3 mmHg (range 1.1-13.8 mmHg), and 7% of valves had moderate regurgitation. DISCUSSION: Semilunar heart valves transplanted in infancy as part of a heart transplant demonstrate statistically significant growth and excellent function after 10 years. This predicts excellent long-term outcomes of partial heart transplants.

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.

Transcatheter pulmonary valve replacement after pulmonary homograft dysfunction.

Pulmonary homograft dysfunction is challenging to treat in patients with a previous Ross procedure, and results in significant morbidity and mortality in case of reoperation. We report the case of a patient with early severe pulmonary homograft stenosis 18 months after a Ross procedure and successful management using transcatheter pulmonary valve replacement.

Matched comparison of decellularized homografts and bovine jugular vein conduits for pulmonary valve replacement in congenital heart disease.

For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures. 319 DPH patients were matched to 319 BJV patients; the mean age of BJV patients was 15.3 (SD 9.5) years versus 19.1 (12.4) years in DPH patients (p = 0.001). The mean conduit diameter was 24.5 (3.5) mm for DPH and 20.3 (2.5) mm for BJV (p < 0.001). There was no difference in survival rates between the two groups after 10 years (97.0 vs. 98.1%, p = 0.45). The rate of freedom from endocarditis was significantly lower for BJV patients (87.1 vs. 96.5%, p = 0.006). Freedom from explantation was significantly lower for BJV at 10 years (81.7 vs. 95.5%, p = 0.001) as well as freedom from any significant degeneration at 10 years (39.6 vs. 65.4%, p < 0.001). 140 Patients, matched for age, heart defect type, prior procedures, and conduit sizes of 20-22 mm (± 2 mm), were compared separately; mean age BJV 8.7 (4.9) and DPH 9.5 (7.3) years (p = n.s.). DPH showed 20% higher freedom from explantation and degeneration in this subgroup (p = 0.232). Decellularized pulmonary homografts exhibit superior 10-year results to bovine jugular vein conduits in PVR.

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.

Ross procedure with personalized external aortic root support.

The Ross-Personalized External Aortic Root Support procedure is a surgical aortic valve replacement technique in which the autologous pulmonary valve is transposed in the aortic position to replace the malfunctioning aortic valve and a homograft is implanted in the pulmonary position. To prevent autograft dilatation, a Personalized External Aortic Root Support prosthesis is included in the proximal autograft anastomosis and wrapped around the ascending aorta. The aorta is transected transversely, the aortic valve is resected, and the coronary arteries are mobilized and cut out of the sinuses, leaving a rim. The pulmonary autograft is harvested by transecting the pulmonary artery and part of the right ventricular outflow tract. The autograft is approximated to the aortic root and inverted inside the ventricle. The proximal anastomosis is performed including the prosthesis between the aortic root and the autograft. The coronary buttons are threaded through appropriately positioned and sized holes in the prosthesis and reimplanted into the autograft. The ascending aorta is appropriately adapted and anastomosed with the distal autograft. When the patient is off cardiopulmonary bypass, the prosthesis can be closed longitudinally and is anchored to the distal aortic adventitia.

The Ross procedure versus repair for treatment of a unicuspid aortic valve in adults†.

OBJECTIVES: Aortic stenosis or regurgitation in patients with a unicuspid valve morphology requires interventions early in life. We have performed either primary valve repair or the Ross procedure. The goal of this study was to compare the midterm results of repair and pulmonary autograft replacement. METHODS: Between December 1998 and April 2022, a total of 345 patients (77% male; mean age 34 ± 9.7 years) underwent treatment of a unicuspid aortic valve. Patients were excluded if they were <18 years (n = 84) or >54 years (n = 3) at the time of the operation. The remaining cohort was divided into 2 groups: 167 (64%) patients underwent valve repair; 91 (36%) patients underwent pulmonary autograft replacement.The indications for surgery were aortic regurgitation (n = 104), aortic stenosis (n = 45), combined disease (n = 103) and endocarditis (n = 6). Fifty-one patients had root dilatation (>43 mm) with aortic regurgitation (repair n = 23; Ross n = 28). Mean follow-up was 5.9 years (SD: 5 years) [range 0.1-22.3 years]. RESULTS: There were 1 early and 3 late deaths; 47 patients required reintervention. Survival at 10 years was 95% in the Ross group and 97% after valve repair (P = 0.769). Freedom from reintervention at 10 years was 98% in the Ross group and 80% after valve repair (P = 0.012). A receiver operating characteristics curve analysis showed a trend towards better durability in patients < 26 years. CONCLUSIONS: The ideal treatment of the unicuspid aortic valve remains debatable. Repair of a unicuspid valve can be considered a bridge to pulmonary autograft replacement, at least in younger patients. The appropriate times to replace and to repair require further investigation.

Autograft reoperations after the Ross procedure.

OBJECTIVES: After a Ross procedure, autograft failure can occur. At reoperation, repair of the autograft preserves the advantages of the Ross procedure. The aim of this retrospective study was to assess mid-term results after reoperation of a failed autograft. METHODS: Between 1997 and 2022, 30 consecutive patients (83% male; age 41 ± 11 years) underwent autograft reintervention between 60 days and 24 years (median 10 years) after a Ross procedure. The initial technique varied, full-root replacement (n = 25) being the most frequent. The indication for reoperation was isolated autograft regurgitation (n = 7), root dilatation (>43 mm) with (n = 17) or without (n = 2) autograft regurgitation, mixed dysfunction (n = 2) and endocarditis (n = 2). In 4 instances, the valve was replaced by valve (n = 1) or combined valve and root replacement (n = 3). Valve-sparing procedures consisted of isolated valve repair (n = 7) or root replacement (n = 19), and tubular aortic replacement. Cusp repair was performed in all but 2. Mean follow-up was 5.4 ± 6 years (35 days to 24 years). RESULTS: Mean cross-clamp and perfusion times were 74 ± 26 and 132 ± 64 min. There were 2 perioperative deaths (7%; both valve replacement) and 2 patients died late (32 days to 1.2 years postoperatively). Freedom from cardiac death at 10 years was 96% after valve repair and 50% after replacement. Two patients required reoperation (1.68 and 16 years) following repair. One underwent valve replacement for cusp perforation, the other, root remodelling for dilatation. Freedom from autograft reintervention at 15 years was 95%. CONCLUSIONS: Autograft reoperations after the Ross procedure can be performed as valve-sparing operations in the majority of cases. With valve-sparing, long-term survival and freedom from reoperation are excellent.

Partial heart transplantation for pediatric heart valve dysfunction: A clinical trial protocol.

Congenital heart defects are the most common type of birth defects in humans and frequently involve heart valve dysfunction. The current treatment for unrepairable heart valves involves valve replacement with an implant, Ross pulmonary autotransplantation, or conventional orthotopic heart transplantation. Although these treatments are appropriate for older children and adults, they do not result in the same efficacy and durability in infants and young children for several reasons. Heart valve implants do not grow with the. Ross pulmonary autotransplants have a high mortality rate in neonates and are not feasible if the pulmonary valve is dysfunctional or absent. Furthermore, orthotopic heart transplants invariably fail from ventricular dysfunction over time. Therefore, the treatment of irreparable heart valves in infants and young children remains an unsolved problem. The objective of this single-arm, prospective study is to offer an alternative solution based on a new type of transplant, which we call "partial heart transplantation." Partial heart transplantation differs from conventional orthotopic heart transplantation because only the part of the heart containing the heart valve is transplanted. Similar to Ross pulmonary autotransplants and conventional orthotopic heart transplants, partial heart transplants contain live cells that should allow it to grow with the recipient child. Therefore, partial heart transplants will require immunosuppression. The risks from immunosuppression can be managed, as seen in conventional orthotopic heart transplant recipients. Stopping immunosuppression will simply turn the growing partial heart transplant into a non-growing homovital homograft. Once this homograft deteriorates, it can be replaced with a durable adult-sized mechanical implant. The protocol for our single-arm trial is described. The ClinicalTrials.gov trial registration number is NCT05372757.

Ex vivo biomechanical analysis of the Ross procedure using the modified inclusion technique in a 3-dimensionally printed left heart simulator.

OBJECTIVE: The inclusion technique was developed to reinforce the pulmonary autograft to prevent dilation after the Ross procedure. Anticommissural plication (ACP), a modification technique, can reduce graft size and create neosinuses. The objective was to evaluate pulmonary valve biomechanics using the inclusion technique in the Ross procedure with and without ACP. METHODS: Seven porcine and 5 human pulmonary autografts were harvested from hearts obtained from a meat abattoir and from heart transplant recipients and donors, respectively. Five additional porcine autografts without reinforcement were used as controls. The Ross procedure was performed using the inclusion technique with a straight polyethylene terephthalate graft. The same specimens were tested both with and without ACP. Hemodynamic parameter data, echocardiography, and high-speed videography were collected via the ex vivo heart simulator. RESULTS: Porcine autograft regurgitation was significantly lower after the use of inclusion technique compared with controls (P < .01). ACP compared with non-ACP in both porcine and human pulmonary autografts was associated with lower leaflet rapid opening velocity (3.9 ± 2.4 cm/sec vs 5.9 ± 2.4 cm/sec; P = .03; 3.5 ± 0.9 cm/sec vs 4.4 ± 1.0 cm/sec; P = .01), rapid closing velocity (1.9 ± 1.6 cm/sec vs 3.1 ± 2.0 cm/sec; P = .01; 1.8 ± 0.7 cm/sec vs 2.2 ± 0.3 cm/sec; P = .13), relative rapid opening force (4.6 ± 3.0 vs 7.7 ± 5.2; P = .03; 3.0 ± 0.6 vs 4.0 ± 2.1; P = .30), and relative rapid closing force (2.5 ± 3.4 vs 5.9 ± 2.3; P = .17; 1.4 ± 1.3 vs 2.3 ± 0.6; P = .25). CONCLUSIONS: The Ross procedure using the inclusion technique demonstrated excellent hemodynamic parameter results. The ACP technique was associated with more favorable leaflet biomechanics. In vivo validation should be performed to allow direct translation to clinical practice.

Complexity and Outcome of Reoperations After the Ross Procedure in the Current Era.

BACKGROUND: The Ross procedure has several advantages, but the need for reintervention is inevitable. The aim of this study was to examine the complexity and outcomes of reoperation after the Ross procedure. METHODS: Retrospective chart review was performed of patients with a prior Ross procedure who underwent reoperation at our institution from September 1991 to January 2021. Demographic, echocardiographic, surgical, and perioperative data were collected. Descriptive statistical and regression analyses were performed. RESULTS: A total of 105 patients underwent a reoperation at Mayo Clinic after the initial Ross procedure performed at our institution (n = 16; 16.2%) or elsewhere (n = 83; 83.8%). Mean age at the Ross procedure was 27 ± 17 years, and mean age at reoperation at our institution was 37 ± 19 years. Indications for surgical procedure varied, but 64% had autograft regurgitation as 1 of their indications for reoperation. Autograft interventions were performed in 78 patients (74.2%). Pulmonary valve or conduit replacement was performed in 56 patients (53.3%). Double root replacement was performed in 11 patients (10.5%). Aortic reconstruction was performed in 37 patients (38.4%). There were 5 early deaths (5%). During a median follow-up of 6.25 years (3 months-24 years), late deaths occurred in 14 patients (13.1%). Patients with ejection fraction <30% on preoperative echocardiography had shorter duration between the Ross procedure and subsequent reoperation (P = .03). CONCLUSIONS: Reoperations after the Ross procedure are performed for a wide range of indications, with most due to autograft dysfunction. The number of early deaths is not low. Reoperation after the Ross procedure should be advised before left ventricular systolic dysfunction.

Long-term outcomes with the pulmonary autograft inclusion technique in adults with bicuspid aortic valves undergoing the Ross procedure.

OBJECTIVE: To compare outcomes with wrapped (pulmonary autograft inclusion) versus unwrapped techniques in adults with bicuspid aortic valves undergoing the Ross procedure. METHODS: Between 1992 and 2019, 129 adults with bicuspid aortic valves (aged ≥18 years) underwent the Ross procedure by a single surgeon. Patients were divided into those without autograft inclusion (unwrapped, n = 71) and those with autograft inclusion (wrapped, n = 58). Median follow-up was 10.3 years (interquartile range, 3.0-16.8 years). Need for autograft reintervention was analyzed using competing risks. RESULTS: Pre- and intraoperative characteristics as well as 30-day morbidity or mortality did not differ between cohorts. Survival at 1, 5, and 10 years, respectively, was 97.2%, 97.2%, and 95.6% in the unwrapped cohort and 100%, 100%, and 100% in the wrapped cohort (P = .15). Autograft valve failure occurred in 25 (35.2%) of the unwrapped and 3 (5.2%) of the wrapped patients. Competing risks analysis demonstrated the wrapped cohort to have a lower need for autograft reintervention (subhazard ratio, 0.28, 95% confidence interval, 0.08-0.91; P = .035). The cumulative incidence of autograft reintervention (death as a competing outcome) at 1, 5, and 10 years, respectively, was 10.2%, 14.9%, and 26.8% in the unwrapped cohort and 4.0%, 4.0%, and 4.0% in the wrapped cohort. CONCLUSIONS: In adults with bicuspid aortic valves, the Ross procedure with pulmonary autograft inclusion stabilizes the aortic root preventing dilatation and reduces the need for reoperation. The autograft inclusion technique allows the Ross procedure to be performed in this population with excellent long-term outcomes.

Biomechanical Engineering Analysis of Pulmonary Valve Leaflet Hemodynamics and Kinematics in the Ross Procedure.

The Ross procedure using the inclusion technique with anticommissural plication (ACP) is associated with excellent valve hemodynamics and favorable leaflet kinematics. The objective was to evaluate individual pulmonary cusp's biomechanics and fluttering by including coronary flow in the Ross procedure using an ex vivo three-dimensional-printed heart simulator. Ten porcine and five human pulmonary autografts were harvested from a meat abattoir and heart transplant patients. Five porcine autografts without reinforcement served as controls. The other autografts were prepared using the inclusion technique with and without ACP (ACP and NACP). Hemodynamic and high-speed videography data were measured using the ex vivo heart simulator. Although porcine autografts showed similar leaflet rapid opening and closing mean velocities, human ACP compared to NACP autografts demonstrated lower leaflet rapid opening mean velocity in the right (p = 0.02) and left coronary cusps (p = 0.003). The porcine and human autograft leaflet rapid opening and closing mean velocities were similar in all three cusps. Porcine autografts showed similar leaflet flutter frequencies in the left (p = 0.3) and noncoronary cusps (p = 0.4), but porcine NACP autografts versus controls demonstrated higher leaflet flutter frequency in the right coronary cusp (p = 0.05). The human NACP versus ACP autografts showed higher flutter frequency in the noncoronary cusp (p = 0.02). The leaflet flutter amplitudes were similar in all three cusps in both porcine and human autografts. The ACP compared to NACP autografts in the Ross procedure was associated with more favorable leaflet kinematics. These results may translate to the improved long-term durability of the pulmonary autografts.

Outcomes of redo operations after the Ross procedure.

BACKGROUND: The Ross procedure is not commonly performed, owing to the procedural complexity and the risk of autograft and/or homograft reoperation. This study examined outcomes of patients undergoing Ross reinterventions at a dedicated Ross center. METHODS: We retrospectively reviewed 225 consecutive patients who underwent a Ross procedure between 1994 and 2019. Index and redo operation characteristics and outcomes were compared between patients with and those without redo operations. Multivariate analysis was used to identify independent predictors of Ross-related reinterventions. Survival was estimated with Kaplan-Meier analysis. RESULTS: Sixty-six patients (29.3%) required redo Ross surgery, 41 patients (18.2%) underwent autograft reoperation only, 8 patients (3.6%) had a homograft reintervention, and 17 patients (7.6%) had both autograft and homograft reoperations (12 as a combined procedure and 5 as sequential procedures). The mean time to reintervention was 11 ± 6 years for autograft reoperations and 12 ± 7 years for homograft reoperations. Patients who underwent Ross-related reinterventions were younger (mean, 38 ± 11 years vs 43 ± 11 years; P < .01) and had a higher rate of New York Heart Association class III/IV (56% vs 38%; P = .02) at the index Ross procedure. Most patients undergoing autograft reintervention had aortic insufficiency and/or aneurysm (98.2%; 57 of 58). The primary reason for homograft reintervention was pulmonary stenosis (92%; 23 of 25). The operative mortality of Ross reintervention was 1.5% (1 of 66). Survival at 15 years was similar in patients who required a redo operation and those who did not (91.2% vs 93.9%; P = .23). CONCLUSIONS: Ross reinterventions can be performed safely and maintain patients at the normal life expectancy restored by the index Ross procedure up to 15 years at experienced centers.

Outcomes of the Ross procedure in young adults with previous aortic valve interventions.

OBJECTIVES: Contemporarily modified Ross procedure continues to deliver excellent outcomes and remains part of the treatment strategy for aortic valve disease in the young adult population. The aim of this study was to assess whether Ross procedure carried out as a second or subsequent intervention for aortic valve disease carries similar risk and long-term benefit, when compared to Ross procedure for the first-time aortic valve replacement. METHODS: A total of 158 patients aged 16-60 years from a single congenital cardiac centre between 1997 and 2020 were included. The sample was split into 2 subgroups, based on the history of previous aortic valve interventions prior to the Ross procedure. Primary outcomes were defined as survival and pulmonary autograft failure. Coarsened exact matching was used to balance for covariates. RESULTS: A total of 103 patients underwent primary Ross and 55 underwent secondary Ross with a mean follow-up of 7.8 years. Twenty-two patients underwent 28 reoperations during follow-up. Forty-nine well-matched pairs were obtained through matching. Freedom from pulmonary autograft failure at 10 years was 84.5% in the primary group vs 100% in the secondary group (P = 0.021). Five- and ten-year survival were identical, 97.5% in the primary group vs 95.6% in the secondary group (P = 0.53). Male sex and era were found to be predictors of neoaortic root dilatation. CONCLUSIONS: The lower incidence of graft failure seen in secondary Ross could justify a stepwise approach to aortic valve intervention. Ross procedure delivers excellent outcomes in the adult population with no difference in survival for primary or secondary Ross.