Long-Term Outcomes Following the Ross Procedure in Neonates and Infants: A Multi-Institutional Analysis.

OBJECTIVES: For neonates and infants with aortic valve pathology, the Ross procedure has historically been associated with high rates of morbidity and mortality. Data regarding long-term durability are lacking. METHODS: The international, multi-institutional Ross Collaborative included six tertiary-care centers. Infants who received a Ross operation between 1996-2016 (allowing a minimum five years of follow-up) were retrospectively identified. Serial echocardiograms were examined to study evolution in neoaortic size and function. RESULTS: Primary diagnoses for the 133 patients (n=30 neonates) included isolated aortic stenosis (AS; 14%, n=19), Shone complex (14%, n=19), and AS+other (excluding Shone complex; n=95, 71%) including arch obstruction (n=55), left ventricular hypoplasia (n=9), and mitral disease (>moderate stenosis or regurgitation, n=31). At the time of Ross, median age was 96 (IQR 36-186) days and median weight was 4.4 (3.6-6.5) kg. In-hospital mortality occurred in 13/133 (10%) patients (4/30 [13%] neonates). Post-discharge mortality occurred in 10/120 (8%) patients at a median 298 days post-Ross. Post-Ross neoaortic dilatation occurred, peaking at 4-5 standard deviations above normal at 2-3 years before returning to near-baseline z-score at a median follow-up of 11.5 [6.4-17.4] years. Autograft/LVOT reintervention was required in 5/120 (4%) patients at a median 10.3 [4.1-12.8] years. Freedom from >moderate neoaortic regurgitation (AR) was 86% at 15 years. CONCLUSIONS: Neonates and infants experience excellent post-discharge survival and long-term freedom from autograft reintervention and AR following Ross. Neoaortic dilatation normalizes in this population in the long-term. Increased consideration should be given to Ross in neonates and infants with aortic valve disease.

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.

Long-term autograft dilation and durability after the Ross procedure are similar in infants, children, and adolescents with primary aortic stenosis.

BACKGROUND: Autograft durability and remodeling are thought to be superior in younger pediatric patients after the Ross operation. We sought to delineate the fate of autografts across the pediatric age spectrum in patients with primary aortic stenosis (AS). METHODS: We retrospectively reviewed patients age ≤18 years with primary AS who underwent the Ross operation between 1993 and 2020. Patients were categorized by age. The primary endpoint was autograft dimensional change, and secondary endpoints were severe neo-aortic insufficiency (AI) and autograft reintervention. RESULTS: A total of 119 patients underwent the Ross operation, including 37 (31.1%) in group I (age <18 months), 24 (20.2%) in group II (age 18 months-8 years), and 58 (48.7%) in group III (age 8-18 years). All groups exhibited similar annular growth rates within the first 5 postoperative years, followed by a collective decrease in annulus growth rates from year 5 to year 10. Group III experienced rapid sinus dilation in the first 5 years, followed by stabilization of the sinus z-score from year 5 to year 10, whereas groups I and II demonstrated stable sinus z-scores over 10 years. There were 4 early deaths (3.4%) and 2 late deaths (1.7%) at a median follow-up of 8.1 years (range, 0.01-26.3 years). At 15 years, the incidences of severe neo-AI (0.0 ± 0.0% vs 0.0 ± 0.0% vs 3.9 ± 3.9%; P = .52) and autograft reintervention (8.4 ± 6.0% vs 0.0 ± 0.0% vs 2.4 ± 2.4%; P = .47) were similar in the 3 groups. CONCLUSIONS: Age at the time of Ross operation for primary AS does not influence long-term autograft remodeling or durability. Other physiologic or technical factors are likely greater determinants of autograft fate.

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.

Gemella sanguinis Infective Endocarditis-Challenging Management of an 8-Year-Old with Duchenne Dystrophy and Undiagnosed Congenital Heart Disease: A Case Report.

Congenital heart disease (CHD) remains a predisposing cardiac condition for infective endocarditis (IE). Case report: We present the case of 8-year-old boy with no known pre-existing cardiac disease diagnosed with infective endocarditis (IE) with Gemella sanguinis. After admission, he underwent transthoracic echocardiography (TTE), which revealed the presence of Shone syndrome with a bicuspid valve, mitral parachute valve and severe aortic coarctation. He developed a paravalvular aortic abscess with severe aortic regurgitation and left ventricle (LV) systolic dysfunction for which he required a complex surgical intervention after six weeks of antibiotic treatment, consisting of Ross operation and coarctectomy, with a complicated postoperative course, cardiac arrest and ECMO support for five days. The evolution was slow and favorable, with no significant residual valvular lesions. However, persistent LV systolic dysfunction and increased muscle enzymes required further investigation to establish a genetic diagnosis of Duchenne disease. As Gemella is not considered a frequent pathogen of IE, no current guidelines refer specifically to it. Additionally, the predisposing cardiac condition of our patient is not currently classified as "high-risk" for IE; this is not considered an indication for IE prophylaxis in the current guidelines. Conclusion: This case illustrates the importance of accurate bacteriological diagnosis in infective endocarditis and poses concerns regarding the necessity of IE prophylaxis in "moderate risk" cardiac conditions such as congenital valvular heart disease, especially aortic valve malformations.

Long-term Outcomes of the Ross Procedure for Young Patients with Aortic Valve Disease.

To define current role of the Ross operation in young patients, the outcome in those followed longer than 20 years were assessed. Between 1994 and 2020, 81 consecutive patients, 70 of 11 male and/or female, mean age 27 years underwent Ross procedure, accruing 20 years of follow-up or longer. Sixty-four had bicuspid valve (79%) and 54 (67%) aortic insufficiency, while 15 (19%) had undergone prior operations. Surgery consisted in root replacement in 53 patients, cylinder inclusion in 20 and sub-coronary graft in 8. There were 7 late deaths in 80 hospital survivors (median follow-up 21 years, IQR 20-23), with 88% ± 5% survival at 25 years. Thirty-four patients required left, 6 left and/or right and 1 right heart valve reoperation, on average 13 years after Ross procedure. Reoperation was valve-sparing in 18 (45%) patients and valve and/or root replacement in 22. Ten (24%) reoperated patients required a second reoperation 18 years after Ross procedure. Freedom from autograft reoperation was 46% ± 6%, while from autograft valve replacement was 60% ± 7%, thanks to autograft valve-sparing. Freedom from isolated right valve reoperation was 98% ± 4%. No mortality was associated with any of the 51 reoperations. Root technique was associated with reoperation (P = 0.024). Age at follow-up was 50 years (IQR 36-60), with 70 (96%) patients in NYHA class I and 6 (55%) women carrying out pregnancies. Young patients undergoing the Ross procedure enjoy unprecedented survival well into the third decade of follow-up, even when faced with reoperation. At 25 years risk of autograft reoperation is consistent, while negligible for homograft. Technical improvements at operation and valve-sparing at reoperation may prolong autograft valve durability.

Ross Operation in Pediatric Population: Impact of the Surgical Timing and the Native Pulmonary Diameter on the Outcome.

Aortic valve replacement early in life may be inevitable. Ross operation, until present day, remains the favorite surgical option in pediatrics with irreparable aortic valve disease. Nonetheless, the necessity for re-operation was always its principal limitation due to aortic valve failure or homograft degeneration. We present our 25 years of experience in the pediatric population. From August 1994 until June 2018, 157 children below 18 years underwent the Ross operation. This retrospective review aims at assessing the long-term outcomes, as well as the risk factors for re-operation after Ross procedure. Median age was 10.9 years, of which seven patients were infants, 79 children, and 71 adolescents. The median follow-up time was 14 years. Hospital mortality was 0.6%. Freedom from autograft re-operation for children was 96.7% and 94.1% at 10 and 20 years, respectively; whereas for adolescents, it was 92.6% and 74.9% at 10 and 20 years. For children, freedom from homograft re-operation was 92.5%, 83.5%, and 56.2% at 10, 15, and 20 years; while for adolescents, it was 96.8%, 91.8%, and 86.7% at 10, 15, and 20 years. Homograft size (p = 0.008) and childhood (p = 0.05) were risk factors for homograft re-operation. Pulmonary valve diameter > 24 mm (p = 0.044) and adolescence (p = 0.032) were risk factors for autograft re-operation. Our experience demonstrated excellent early and late survival. While children have preferential outcomes concerning autograft re-operation, those who received a smaller homograft had a higher right-sided re-intervention incidence than adolescents. Pulmonary diameter > 24 mm at surgery was an indicator of future autograft failure.

Outcomes of Pregnancy in Women With Bioprosthetic Heart Valves With or Without Valve Dysfunction.

BACKGROUND: Although pregnancy outcomes in women with normally functioning bioprosthetic valves (BPVs) are often good, structural valve dysfunction (SVD) may adversely affect pregnancy outcomes, but this has not been studied. OBJECTIVES: The aim of this study was to examine outcomes in pregnant women with BPVs and the association with SVD. METHODS: Pregnancy outcomes in women with BPVs were prospectively collected. Adverse maternal cardiac events (CEs) included cardiac death or arrest, sustained arrhythmia, heart failure, thromboembolism, and stroke. Adverse fetal events were also studied. Determinants of adverse events were examined using logistic regression. RESULTS: Overall, 125 pregnancies in women with BPVs were included, 27% with left-sided and 73% with right-sided BPV. SVD was present in 27% of the pregnancies (44% with left-sided BPVs vs 21% with right-sided BPVs; P = 0.009). CEs occurred in 13% of pregnancies and were more frequent in women with SVD compared with those with normally functioning BPVs (26% vs 8%; P = 0.005). CEs were more common in women with left-sided BPVs with SVD vs normally functioning BPVs (47% vs 5%; P = 0.01) but not in women with right-sided BPVs (11% in those with SVD vs 8% in those without SVD; P = 0.67). Left-sided SVD (P = 0.007), maternal age >35 years (P = 0.001), and a composite variable of "high-risk" features (P = 0.006) were predictors of CEs. Fetal events occurred in 28% of pregnancies. CONCLUSIONS: In this cohort of young women with BPVs, SVD was present in 27% at the first antenatal visit and negatively affected pregnancy outcomes. In particular, SVD of left-sided BPVs was associated with high rates of adverse outcomes.

Biomechanics of Pulmonary Autograft as Living Tissue: A Systematic Review.

INTRODUCTION: The choice of valve substitute for aortic valve surgery is tailored to the patient with specific indications and contraindications to consider. The use of an autologous pulmonary artery (PA) with a simultaneous homograft in the pulmonary position is called a Ross procedure. It permits somatic growth and the avoidance of lifelong anticoagulation. Concerns remain on the functionality of a pulmonary autograft in the aortic position when exposed to systemic pressure. METHODS: A literature review was performed incorporating the following databases: Pub Med (1996 to present), Ovid Medline (1958 to present), and Ovid Embase (1982 to present), which was run on 1 January 2022 with the following targeted words: biomechanics of pulmonary autograft, biomechanics of Ross operation, aortic valve replacement and pulmonary autograph, aortic valve replacement and Ross procedure. To address the issues with heterogeneity, studies involving the pediatric cohort were also analyzed separately. The outcomes measured were early- and late-graft failure alongside mortality. RESULTS: a total of 8468 patients were included based on 40 studies (7796 in pediatric cohort and young adult series and 672 in pediatric series). There was considerable experience accumulated by various institutions around the world. Late rates of biomechanical failure and mortality were low and comparable to the general population. The biomechanical properties of the PA were superior to other valve substitutes. Mathematical and finite element analysis studies have shown the potential stress-shielding effects of the PA root. CONCLUSION: The Ross procedure has excellent durability and longevity in clinical and biomechanical studies. The use of external reinforcements such as semi-resorbable scaffolds may further extend their longevity.

Right coronary artery originating from the left ventricular outflow tract diagnosed after a Ross procedure: a case report.

Background: Anomalous coronary origin from the left ventricular outflow tract (LVOT) is an exceedingly rare condition thought to be associated with the bicuspid aortic valve (BAV). While the malignant presentation of this entity has been described, its pathophysiology and diagnostic evaluation are poorly understood. Case summary: A 33-year-old woman status post Ross procedure in childhood for congenital aortic stenosis due to BAV with presumed common origin of right and left coronary arteries based on single coronary ostium seen on aortic valve inspection, presented with symptomatic pulmonary regurgitation and stenosis. Invasive left coronary angiography revealed retrograde filling of the right coronary artery (RCA) with systolic washout of contrast indicating a patent RCA ostium. No RCA ostium was found on aortic root injection, but an injection into the LVOT revealed an RCA ostium below the aortic valve. Selective RCA angiography revealed pulsatile antegrade flow down the RCA occurring during systole. There was no anatomic RCA stenosis. We proceeded with valve-in-valve TcPVR. The patient had significant improvement of symptoms and RCA reimplantation was hence deferred. Discussion: This case is the first of an anomalous coronary artery arising from the LVOT diagnosed in a patient after the Ross procedure. Our angiograms shed light on the unusual physiology of coronary filling during systole and ischaemia arising from inadequate perfusion gradient between the left ventricle and the coronary during systole, leading to collateralization despite the lack of anatomic stenosis. We urge consideration of this potentially malignant entity in any symptomatic patient, especially with concomitant BAV.

Biomechanical Analysis of the Ross Procedure in an Ex Vivo Left Heart Simulator.

BACKGROUND: Neo-aortic pulmonary autografts often experience root dilation and valve regurgitation over time. This study seeks to understand the biomechanical differences between aortic and neo-aortic pulmonary roots using a heart simulator. METHODS: Porcine aortic, neo-aortic pulmonary, and pulmonary roots (n = 6) were mounted in a heart simulator (parameters: 100 mm Hg, 37 °C, 70 cycles per minute, 5.0 L/min cardiac output). Echocardiography was used to study root distensibility (percentage change in luminal diameter between systole and diastole) and valve function. Leaflet motion was tracked with high-speed videography. After 30 min in the simulator, leaflet thickness (via cryosectioning), and multiaxial modulus (via lenticular hydrostatic deformation testing) were obtained. RESULTS: There were no significant differences between aortic and neo-aortic pulmonary leaflet motion, including mean opening velocity (218 vs 248 mm/s, P = .27) or mean closing velocity (116 vs 157 mm/s, P = .12). Distensibility was similar between aortic (8.5%, 1.56 mm) and neo-aortic pulmonary (7.8%, 1.12 mm) roots (P = .59). Compared to virgin controls, native pulmonic roots exposed to systemic pressure for 30 min had reduced leaflet thickness (630 vs 385 µm, P = .049) and a reduced Young's modulus (3,125 vs 1,089 kPa, P = .077). In contrast, the aortic roots exposed to pressure displayed no significant difference in aortic leaflet thickness (1,317 vs 1,256 µm, P = .27) or modulus (5,931 vs 3,631 kPa, P = .56). CONCLUSIONS: Neo-aortic pulmonary roots demonstrated equivalence in valve function and distensibility but did experience changes in biomechanical properties and morphology. These changes may contribute to long-term complications associated with the Ross procedure.

The effectiveness and safety of pulmonary autograft as living tissue in Ross procedure: a systematic review.

Background: Reports on effectiveness and safety after the implant of pulmonary autograft (PA) living tissue in Ross procedure, to treat both congenital and acquired disease of the aortic valve and left ventricular outflow tract (LVOT), show variable durability results. We undertake a quantitative systematic review of evidence on outcome after the Ross procedure with the aim to improve insight into outcome and potential determinants. Methods: A systematic search of reports published from October 1979 to January 2021 was conducted (PubMed, Ovid Medline, Ovid Embase and Cochrane library) reporting outcomes after the Ross procedure in patients with diseased aortic valve with or without LVOT. Inclusion criteria were observational studies reporting on mortality and/or morbidity after autograft aortic valve or root replacement, completeness of follow-up >90%, and study size n≥30. Forty articles meeting the inclusion criteria were allocated to two categories: pediatric patient series and young adult patient series. Results were tabulated for a clearer presentation. Results: A total of 342 studies were evaluated of which forty studies were included in the final analysis as per the eligibility criteria. A total of 8,468 patients were included (7,796 in pediatric cohort and young adult series and 672 in pediatric series). Late mortality rates were remarkably low alongside similar age-matched mortality with the general population in young adults. There were differences in implantation techniques as regard the variability in stress and the somatic growth that recorded conflicting outcomes regarding the miniroot vs the subcoronary approach. Discussion: The adaptability of lung autograft to allow for both stress variability and somatic growth make it an ideal conduit for Ross's operation. The use of the miniroot technique over subcoronary implantation for better adaptability to withstand varying degrees of stress is perhaps more applicable to different patient subgroups.

Impact of a structured patient education programme on early diagnosis of prosthetic pulmonary valve endocarditis.

BACKGROUND: Infective endocarditis is a major threat after prosthetic pulmonary valve replacement. Early diagnosis may improve outcomes. METHODS: A structured patient education programme for prevention and early diagnosis of infective endocarditis was developed at our institution since 2016. Time delay between onset of symptoms of prosthetic pulmonary valve endocarditis and its diagnosis (defined as initiation of appropriate high-dose intravenous antibiotic treatment) was compared for patients presenting before (cohort 1) and after (cohort 2) initiation of the patient education programme. RESULTS: Between 2008-2019, 26 patients (median age 24.9, range: 16.8-62.0 years, 73% male) were diagnosed with prosthetic pulmonary valve endocarditis, 13 patients (cohort 1) before (1.7 cases/year) and 13 patients (cohort 2) after June 2016 (3.7 cases/year). There were no differences in baseline characteristics or clinical presentation between the study cohorts. Overall, the median delay between onset of symptoms and diagnosis of infective endocarditis was 6 days (range: 0-133 days) with a significantly longer delay among patients in cohort 1, compared to cohort 2 (25 days, range: 5-133 days versus 3 days, range: 0-13 days, p < 0.0001). A delay of >7 days was documented in 11/13 patients (85%) in cohort 1 as compared to 1/13 (8%) in cohort 2 (p < 0.001). Need for urgent valve replacement or permanent deterioration of prosthetic valve function was higher in cohort 1, compared to cohort 2 (11/13, 85% versus 5/13, 39%; p = 0.041). CONCLUSIONS: Prosthetic pulmonary valve endocarditis is increasingly recognised. A structured patient education programme may improve early diagnosis and clinical outcomes.

Short- and Mid-Term Autograft Outcomes Following the Reinforced Ross Operation.

BACKGROUND: The Ross operation for aortic valve replacement continues to be a controversial option because of concerns related to late autograft dilation and progressive neo-aortic insufficiency. In 2005, the reinforced Ross procedure was described at our institution to address this problem. We aim to analyze the short and mid-term outcomes following this procedure. METHODS: This is a retrospective study of patients who underwent the reinforced Ross operation between 2004 and 2019. A comprehensive chart review was performed. Echocardiograms were independently reviewed by an adult congenital cardiologist. The time to reintervention was evaluated with a Kaplan-Meier curve. Analysis was conducted in JMP 15.1 (SAS Inc., Cary, NC). RESULTS: Twenty-five patients underwent the reinforced Ross operation. Twenty-three patients (92%) had bicuspid aortic valve and the most common indication for surgery was a combination of aortic insufficiency and stenosis (n = 18, 72%). The mean follow-up was 6.1 ± 5.0 years. All patients were alive at the time of follow-up. Six patients (24%), from early in our experience, required subsequent aortic reintervention. Median time to reintervention was 41.8 months (0-81.5 months). Sixteen (64%) patients had less than moderate aortic insufficiency at last follow-up. Additionally, average aortic root measurements remained unchanged. CONCLUSIONS: The reinforced Ross technique was initially proposed as a way to mitigate aortic root dilation seen in the traditional Ross procedure. Our experience suggests an associated learning curve with the majority of aortic reinterventions occurring within the first few years following surgery. Continued follow-up is warranted to assess its long-term durability and functionality.

The reinforced full-root technique for the Ross operation: surgical considerations and operative insights.

BACKGROUND: Surgical treatment of young and middle-aged patients suffering from aortic valve disease remains an unresolved issue due to the limited durability of bioprosthetic heart valve replacements and the valve-related morbidity of patients with mechanical valve substitutes. Theoretically, the "living valve" principle of the Ross operation may represent a potentially viable solution to this dilemma. In this paper, we report on the surgical techniques of the Ross procedure and present long-term post-operative outcomes using the reinforced full-root technique. METHODS: From 1995 to 2020, a total of 832 consecutive patients (mean age, 43.4±13.7 years; 617 males) underwent a Ross operation using the full-root technique. Patients were prospectively monitored with clinical and echocardiographic follow-up. Total follow-up was 9,046 patients-years and was 92% complete. Mean-follow-up was 10.9±6.9 years (range, 0-24.9 years). RESULTS: Survival at twenty years was 92% (95% CI: 90-94%). Freedom from autograft or right ventricle to pulmonary artery connection reoperation at twenty years was 79% (95% CI: 74-85%). Eighty-nine pulmonary autograft reoperations had to be performed in eighty patients; salvage of the pulmonary autograft could be performed in forty-six of them. Fifty-seven patients required sixty-three reoperations on the right ventricle to pulmonary artery connection. Major cerebral bleeding occurred in one patient and neurological events in seventeen patients, respectively. CONCLUSIONS: Over a follow-up interval of up to twenty-five years, the Ross operation with the reinforced full-root technique demonstrated excellent survival in young and middle-aged patients. The rate of pulmonary autograft and right ventricular outflow graft reoperations were low in this patient subset. Therefore, the Ross operation with the reinforced full-root technique represents an enduring and valid treatment option in young and middle-aged patients suffering from aortic valve disease.