Aortic valve repair in a low-birth-weight neonate with poor ventricular function: staged tricuspidization of the unicuspid valve.

Congenital severe isolated aortic stenosis in neonates requires prompt intervention because left ventricular function may deteriorate rapidly. Surgical repair of a stenotic aortic valve in neonates allows debridement of fibrous material and precision commissurotomy. As such, the child would end up with a much better-quality aortic valve compared to the uncontrolled tear that results following balloon dilatation. The meticulous debridement and precise commissurotomy are important in achieving long-term durability of the aortic valve repair, with the expectation that the patient may keep the native aortic valve at least into adolescence or adulthood. If feasible, it is important to avoid placement of patches while repairing the valve, so that the growth potential of the cusps is preserved. The valve could be revisited and repaired further, so that, ideally, the native valve could be retained for life, thus avoiding aortic valve replacement entirely. We present a low-birth-weight neonate with a dysplastic unicuspid aortic valve, severe aortic valve stenosis and decreased left ventricular function who underwent repair of the aortic valve.

Long-Term Results of Congenital Aortic Stenosis Treatment in the Era of Percutaneous Balloon Valvuloplasty: Up to 33 Years Follow-Up.

Background The goal of this study was to evaluate long-term results of percutaneous balloon valvuloplasty (BVPL) used exclusively for initial management of congenital aortic stenosis in children. Methods and Results A total of 409 consecutive pediatric patients (134 newborns, 275 older patients) who underwent BVPL as initial treatment of aortic stenosis in a single nationwide pediatric center were subjected to a retrospective follow-up study. The resulting follow-up time reached a median of 18.5 (interquartile range, 12.2-25.1) years. Successful BVPL was defined by residual Doppler gradient <70/40 (systolic/mean) mm Hg. The primary end point was death; secondary end points included any valve reintervention, balloon revalvuloplasty, any aortic valve surgery, and aortic valve replacement, respectively. BVPL effectively reduced the peak and mean gradient both immediately and at the latest follow-up (P<0.001). There was significant procedure-related progression of aortic insufficiency (P<0.001). Higher aortic annulus z score was predictive for severe aortic regurgitation (P<0.05) and lower z score for insufficient gradient reduction (P<0.05). The actuarial probability of survival/survival free from any valve reintervention was 89.9%/59.9%, 85.9%/35.2%, and 82.0%/26.7% at 10, 20, and 30 years after first BVPL, respectively. Left ventricular dysfunction or arterial duct dependency as the indication for BVPL was predictive of both worse survival and survival free from any reintervention (P<0.001). Lower aortic annulus z score and lower balloon-to-annulus ratio were predictive of a need for revalvuloplasty (P<0.001). Conclusions Percutaneous BVPL provides good initial palliation. In patients with hypoplastic annuli and left ventricular or mitral valve comorbidity, the results are less favorable.

Case report: Aortic valve endocarditis and recurrent pulmonary valve stenosis.

BACKGROUND: We discuss a rare case of an adult patient with different pathologies involving the aortic and pulmonary valves in need of surgery. CASE PRESENTATION: The patient had a history of congenital PV stenosis and surgical valvuloplasty. Almost 50 years later the patient underwent a complex second heart surgery due to infective endocarditis of the aortic valve and high-grade restenosis of the pulmonary valve. Replacement of the aortic and pulmonary valve, as well as reconstruction of the RVOT and closure of a persistent foramen ovale, followed. Postoperative course was uneventful and the patient was discharged home a week after surgery. CONCLUSION: Simultaneous surgery of pulmonary and aortic valves due to different pathologies is rare but can be performed successfully even in advanced age and can improve quality of life.

Immediate results of primary balloon dilation for congenital aortic valve stenosis predict the mid-term outcome.

BACKGROUND: Balloon valvuloplasty is the primary treatment for congenital aortic valve stenosis in our centre. We sought to determine independent predictors of reintervention (surgical repair or repeated balloon dilation) after primary valvuloplasty. METHODS: We retrospectively studied patients with congenital aortic valve stenosis who underwent balloon valvuloplasty during 2004-2018. The following risk factors were analysed: aortic valve insufficiency after balloon valvuloplasty >+1/4, post-procedural gradient across the aortic valve ≥35 mmHg, pre-interventional gradient across the valve, annulus size, use of rapid pacing, and balloon/annulus ratio. Primary outcome was aortic valve reintervention. RESULTS: In total, 99 patients (median age 4 years, range 1 day to 26 years) underwent balloon valvuloplasty for congenital aortic valve stenosis. After a mean follow-up of 4.0 years, 30% had reintervention. Adjusted risks for reintervention were significantly increased in patients with post-procedural aortic insufficiency grade >+1/4 and/or residual gradient ≥35 mmHg (HR 2.55, 95% CI 1.13-5.75, p = 0.024). Pre-interventional gradient, annulus size, rapid pacing, and balloon/annulus ratio were not associated with outcome. CONCLUSION: Post-procedural aortic valve insufficiency grade >+1/4 and/or residual gradient ≥35 mmHg in patients undergoing balloon valvuloplasty for congenital aortic valve stenosis confers an increased risk for reintervention in mid-term follow-up.

Long-term outcomes of primary aortic valve repair for isolated congenital aortic stenosis in children.

OBJECTIVE: We aimed to assess the long-term outcomes of children with isolated congenital aortic stenosis who underwent primary aortic valve repair. METHODS: Records of all children (n = 111) with isolated congenital aortic stenosis who underwent primary aortic valve repair between 1980 and 2016 were reviewed. An optimal operative outcome consisted of a residual left ventricular outflow tract peak systolic gradient <35 mm Hg and trivial or less aortic insufficiency. RESULTS: Median age at surgery was 0.4 years (interquartile range, 1 month-7.9 years) and median weight at surgery was 7.0 kg (interquartile range, 3.7-25.0 kg). Fifty-two patients (46.8%; 52/111) underwent aortic valve repair with the use of patch material. Early mortality was 0.9% (1/111). Late mortality was 0.9% (1/110). Freedom from aortic valve reoperation was 52.1% (95% CI, 38.7-63.8) at 10 years. Freedom from aortic valve replacement was 67.9% (95% CI, 55.4-77.5) at 10 years. An optimal outcome was achieved in 48 patients (43.2%; 48/111). At 10 years, freedom from aortic valve reoperation was 78.2% (95% CI, 63.1-87.8) in patients with an optimal outcome, compared with 39.4% (95% CI, 22.8-55.6) in those with a suboptimal outcome (P = .03). Tricuspid aortic valve was associated with a suboptimal outcome (P = .01). CONCLUSIONS: Aortic valve repair achieves relief of congenital aortic stenosis with very low early mortality and excellent long-term survival, even in neonates. Although nearly half of the patients required aortic valve reoperation by 10 years, two-thirds of the patients remain free from aortic valve replacement. An optimal outcome was more commonly achieved with bicuspid aortic valves compared with tricuspid aortic valves.

Collagen fiber regulation in human pediatric aortic valve development and disease.

Congenital aortic valve stenosis (CAVS) affects up to 10% of the world population without medical therapies to treat the disease. New molecular targets are continually being sought that can halt CAVS progression. Collagen deregulation is a hallmark of CAVS yet remains mostly undefined. Here, histological studies were paired with high resolution accurate mass (HRAM) collagen-targeting proteomics to investigate collagen fiber production with collagen regulation associated with human AV development and pediatric end-stage CAVS (pCAVS). Histological studies identified collagen fiber realignment and unique regions of high-density collagen in pCAVS. Proteomic analysis reported specific collagen peptides are modified by hydroxylated prolines (HYP), a post-translational modification critical to stabilizing the collagen triple helix. Quantitative data analysis reported significant regulation of collagen HYP sites across patient categories. Non-collagen type ECM proteins identified (26 of the 44 total proteins) have direct interactions in collagen synthesis, regulation, or modification. Network analysis identified BAMBI (BMP and Activin Membrane Bound Inhibitor) as a potential upstream regulator of the collagen interactome. This is the first study to detail the collagen types and HYP modifications associated with human AV development and pCAVS. We anticipate that this study will inform new therapeutic avenues that inhibit valvular degradation in pCAVS and engineered options for valve replacement.

Balloon Valvuloplasty for Congenital Aortic Stenosis: Experience at a Tertiary Center in a Developing Country.

BACKGROUND: Aortic valve stenosis accounts for 3-6% of congenital heart disease. Balloon aortic valvuloplasty (BAV) is the preferred therapeutic intervention in many centers. However, most of the reported data are from developed countries. MATERIALS AND METHODS: We performed a retrospective single-center study involving consecutive eligible neonates and infants with congenital aortic stenosis admitted for percutaneous BAV between January 2005 and January 2016 to our tertiary center. We evaluated the short- and mid-term outcomes associated with the use of BAV as a treatment for congenital aortic stenosis (CAS) at a tertiary center in a developing country. Similarly, we compared these outcomes to those reported in developed countries. RESULTS: During the study period, a total of thirty patients, newborns (n = 15) and infants/children (n = 15), underwent BAV. Left ventricular systolic dysfunction was present in 56% of the patients. Isolated AS was present in 19 patients (63%). Associated anomalies were present in 11 patients (37%): seven (21%) had coarctation of the aorta, two (6%) had restrictive ventricular septal defects, one had mild Ebstein anomaly, one had Shone's syndrome, and one had cleft mitral valve. BAV was not associated with perioperative or immediate postoperative mortality. Immediately following the valvuloplasty, a more than mild aortic regurgitation was noted only in two patients (7%). A none-to-mild aortic regurgitation was noted in the remaining 93%. One patient died three months after the procedure. At a mean follow-up of 7 years, twenty patients (69%) had more than mild aortic regurgitation, and four patients (13%) required surgical intervention. Kaplan-Meier freedom from aortic valve reintervention was 97% at 1 year and 87% at 10 years of follow-up. CONCLUSION: Based on outcomes encountered at a tertiary center in a developing country, BAV is an effective and safe modality associated with low complication rates comparable to those reported in developed countries.

Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.

Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies. Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level. While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease. Here, we tested for spatial localization of N-glycan structures within pediatric congenital aortic valve stenosis. The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS. High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure. RNA-Seq was used to identify regulation of N-glycan related enzymes. The N-glycome was found to be spatially localized in the normal aortic valve, aligning with fibrosa, spongiosa or ventricularis. In AVI diagnosed tissue, N-glycans localized to hypertrophic commissures with increases in pauci-mannose structures. In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group. Three sialylated N-glycans showed common elevation in AS independent of age. On-tissue chemical methods optimized for valvular tissue determined that aortic valve tissue sialylation shows both α2,6 and α2,3 linkages. Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS. This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease.

Surgical Valvuloplasty Versus Balloon Dilation for Congenital Aortic Stenosis in Pediatric Patients.

BACKGROUND: For children with congenital aortic stenosis (AS) who are candidates for biventricular repair, valvuloplasty can be achieved by surgical aortic valvuloplasty (SAV) or by transcatheter balloon aortic dilation (BAD). We aimed to evaluate the longer term outcomes of SAV versus BAD at our institution. METHODS: We retrospectively reviewed the outcomes of 2 months to 18 years old patients who underwent SAV or BAD at our institution between January 1990 and July 2018. Baseline and follow-up characteristics were assessed by echocardiography. Long-term survival, freedom from reintervention, freedom from aortic valve replacement (AVR), and aortic regurgitation were evaluated. RESULTS: A total of 212 patients met inclusion criteria (SAV = 123; BAD = 89). Age, sex, aortic insufficiency (AI), and aortic valve gradient were similar between the groups. At 10 years, 27.9% (19/68) of SAV patients and 58.3% (28/48) of BAD patients had moderate or worse AI (P = .001), and reintervention occurred in 39.2% (29/74) of SAV patients and 78.6% (44/56) of BAD patients (P < .001). Kaplan-Meier analysis revealed overall survival was 96.8% (119/123) for SAV and 95.5% (85/89) for SAV (P = .87). At 10 years, 35% (23/66) of SAV patients and 54% (23/43) of BAD patients underwent AVR (P = .213). CONCLUSIONS: Surgical aortic valvuloplasty demonstrated greater gradient reduction, less postoperative and long-term AI, and a lower reintervention rate at 10 years than BAD. There was no difference in survival or AVR reintervention rate. Surgical aortic valvuloplasty is a durable and efficacious intervention and should continue to be considered a favorable choice for palliation of valvular AS.

Implantation of a decellularized aortic homograft in a child.

The implantation of a decellularized aortic homograft in children and young adults has been shown to be a good alternative to existing surgical approaches. Lower risk of calcification and the potential of growth render a homograft a promising valve substitute. The child presented in this video tutorial is a 10-year-old boy diagnosed with congenital aortic stenosis which was treated by balloon valvuloplasty early in life. Current echocardiographic findings show severe aortic regurgitation and stenosis. The tutorial provides detailed insight into how to implant a decellularized aortic homograft as a total root replacement.

Fetal Aortic Valvuloplasty for Evolving Hypoplastic Left Heart Syndrome: A Decision Analysis.

BACKGROUND: Fetal aortic valvuloplasty (FAV) may prevent progression of midgestation aortic stenosis to hypoplastic left heart syndrome. However, FAV has well-established risks, and its survival benefit remains unknown. Our primary aim was to determine whether FAV for midgestation aortic stenosis increases survival from fetal diagnosis to age 6 years. METHODS AND RESULTS: We performed a retrospective analysis of 143 fetuses who underwent FAV from 2000 to 2017 and a secondary analysis of the Pediatric Heart Network Single Ventricle Reconstruction trial. Using these results, we developed a decision model to estimate probability of transplant-free survival from fetal diagnosis to age 6 years and postnatal restricted mean transplant-free survival time. FAV was technically successful in 84% of 143 fetuses with fetal demise in 8%. Biventricular circulation was achieved in 50% of 111 live-born infants with successful FAV but in only 16% of the 19 patients with unsuccessful FAV. The model projected overlapping probabilities of transplant-free survival to age 6 years at 75% (95% CI, 67%-82%) with FAV versus 72% (95% CI, 61%-82%) with expectant fetal management, resulting in a restricted mean transplant-free survival time benefit of 1.2 months. When limiting analyses to the improved FAV experience since 2009 to reflect current practice, (probability of technical success [94%], fetal demise [4%], and biventricular circulation [66%]), the model projected that FAV increased the probability of survival to age 6 years to 82% (95% CI, 73%-89%). Expectant management is favored if risk of fetal demise exceeded 12% or probability of biventricular circulation fell below 26%, but FAV remained favored over plausible recent range of technical success. CONCLUSIONS: Our model suggests that FAV provides a modest, medium-term survival benefit over expectant fetal management. Appropriate patient selection and low risk of fetal demise with FAV are critical factors for obtaining a survival benefit.

Strategies to Minimise Need for Prosthetic Aortic Valve Replacement in Congenital Aortic Stenosis-Value of the Ross Procedure.

To examine the role and outcomes of all interventions for aortic stenosis in children, with focus on freedom from reintervention and the aim to minimise prosthetic aortic valve replacement (pAVR) during childhood. Retrospective analysis of 194 consecutive children who underwent any aortic valve intervention for a biventricular repair strategy at a single institution between 1995 and 2017. Data were obtained from hospital records and follow-up was 100% complete. Over a 22-year period, 194 children underwent total 313 aortic valve procedures: Primary interventions were surgical valvotomy (SV)/surgical repair (SR) in 94 (48.5%), balloon valvuloplasty (BV) in 60 (30.9%), pAVR in 8 (4.1%) and Ross/Ross-Konno procedure in 32 (16.5%). Median age at first intervention was 1.1 years (interquartile range [IQR] 0.1-9.4) and varied with type of intervention: SV/SR were most common in neonates (33, 75%) and infants (35, 68%), whilst BV was most frequent in older children (42, 42%). Operative survival was 99% (2 early deaths, both in neonates with critical aortic stenosis and poor left ventricular function) and 15-year survival was 95%. A Ross procedure was performed in 79 (40.7%) patients over the 15-year study period, 1 of whom required late pAVR for autograft failure. Freedom from any reintervention after SV/SR and BV was 41% and 40% at 10 years, compared to 90% at 10 years with the Ross procedure (P < 0.001). Among neonatal SV/SR and BV, 98% required reintervention during childhood with no difference between groups. Valve morphology did not influence freedom from ultimate valve replacement. In patients who went on to have a Ross procedure, median time from initial intervention to Ross was 2.8 years (IQR 0.1-11.9) in neonates and 6.0 years (IQR 3.1-7.5) in all other age groups. Overall freedom from pAVR was 97% at 10 years and was similar in the SV/SR and BV groups. A strategy of simple valve repair and primary Ross procedure provides excellent survival and good freedom from pAVR. However, reintervention rates after simple interventions for congenital AS are high, especially in younger age groups. The Ross procedure offers the best freedom from reintervention of any technique and wider use of primary Ross in younger age groups should be considered.

Effect of Pressure Recovery on Pressure Gradients in Congenital Stenotic Outflow Lesions in Pediatric Patients-Clinical Implications of Lesion Severity and Geometry: A Simultaneous Doppler Echocardiography and Cardiac Catheter Correlative Study.

BACKGROUND: Doppler pressure gradients (PGs) are routinely used as a surrogate for catheter peak-to-peak gradient (PPG) for referring pediatric patients with aortic stenosis (AS), pulmonary stenosis (PS), and coarctation of the aorta (CoA) for intervention but do not always predict the catheter PPG accurately, which results in misclassification of lesion severity. We hypothesized that recovered pressure (RP) accounts for the discrepancy between Doppler PG and catheter PPG. We aimed to study the occurrence of clinically significant RP in AS, PS, and CoA. METHODS: Simultaneous Doppler and catheter PGs were prospectively measured in 82 patients (median age, 12.2 months; weight, 7.5 kg) with isolated AS (n = 30), PS (n = 24), and CoA (n = 28), and agreement before and after correcting for RP were analyzed. RP was calculated from a fluid dynamic-based equation. Effects of lesion geometry on the magnitude of RP were analyzed. RESULTS: Recovered pressure-corrected Doppler peak instantaneous gradient (PIG) had significantly closer agreement and correlation with the catheter PPG (P < .001) than the uncorrected PIG and mean Doppler gradients. Recovered pressure-corrected Doppler PIG predicted PPG with high specificity and accuracy in all lesions (95% CI, 36%-97% and 85%-100%, respectively, P < .05 for both). RP magnitude was weakly related (r = 0.33 to 0.47) to valve area and inversely related (r = -0.22 to -0.34) to downstream vessel area. CONCLUSIONS: Significant RP occurs in congenital AS, PS, and CoA, accounting for misclassification of lesion severity by Doppler PIG. The RP magnitude is at a maximum in mild to moderate stenotic outflow lesions, with small-size downstream vessels causing the most misclassification of lesion severity by Doppler PIG.

Valvular aortic stenosis in three cats.

Aortic stenosis affects 0.028% of cats in a shelter population, with valvular aortic stenosis compromising almost half of these cases. Of congenital heart diseases reported in cats, aortic stenosis is the second most common one, affecting 17% of these cases. Existing literature on valvular aortic stenosis is scant, and thus, presentation and prognosis of affected animals is poorly understood. In this case series, we describe three cats with confirmed valvular aortic stenosis. All cases were diagnosed echocardiographically, and all three had visible aortic valve leaflet fusion and a poststenotic dilation of the ascending aorta. Congestive heart failure developed in all three cases, and prognosis was poor. This case report highlights the existence of aortic valve dysplasia in cats and may allow clinicians a better understanding of the clinical presentation of this congenital abnormality.

Outcomes Following Balloon Aortic Valvuloplasty Versus Surgical Valvotomy in Congenital Aortic Valve Stenosis: A Meta-Analysis.

BACKGROUND: The optimal treatment for congenital aortic stenosis (AS) has been debated over the past three decades of experience with both balloon aortic valvuloplasty (BAV) and surgical aortic valvotomy (SAV). While BAV has been the mainstay of therapy for children with AS in most centers, recent single-center reports suggest superior results following SAV. METHODS: We queried Medline, EMBASE and Web of Science for eligible studies. RESULTS: A total of 18 studies were included in our meta-analysis: SAV alone (n = 3), BAV alone (n = 10), and both (n = 5). The mean follow-up duration of BAV patients was 6.5 years, while the mean follow-up duration for SAV patients was 7.2 years. Mortality rates following BAV and SAV were 11% (95% CI, 8-14) and 10% (95% CI, 7-15), respectively. Reintervention following initial procedure for treatment of AS was higher following BAV (37% [95% CI, 30-44]) compared with SAV (25% [95% CI, 20-31]). The predominant reintervention for both the BAV and SAV groups was surgery (SAV or aortic valve replacement [AVR]); the surgical reintervention rate was 59% for BAV (95% CI, 51-66) and 75% for SAV (95% CI, 48-91). Mean time to reintervention was shorter for BAV (2.7 years [95% CI, 1.4-4.1]) compared with SAV (6.9 years [95% CI, 4.4-9.4]). AVR following BAV was 20% (95% CI, 17-23) and following SAV was 17% (95% CI, 12-25). Long-term and mid-term follow-up in these studies showed moderate to severe aortic insufficiency (AI) was present in 28% (95% CI, 20-37) and 19% (95% CI, 12-27) in BAV and SAV patients, respectively. CONCLUSIONS: The rate of reintervention following BAV is higher than following SAV. However, survival rates, AVR, and development of late AI following BAV and SAV are equivalent. The costs associated with the two therapies in terms of hospital days and other morbidities should be considered in future comparative studies.

Long-Term Fate of the Neoaortic Root After Neonatal Ross Operation: A Case Series.

The aim of this study is to analyze the adaptation properties of the pulmonary autograft in four infants who underwent the Ross operation before one year of life. The patients underwent serial echocardiographic assessments of the autograft diameters at short- and long-term follow-up and values were reported as the Z scores for normal aortic and pulmonary diameters. At a median follow-up time of 18.5 years (range: 18.2-19.4 years), all the patients are alive, none requiring autograft reinterventions. This series shows excellent adaptation potential of the "infant pulmonary autograph" in the long-term, during somatic growth of the patient.

Coronary Artery Thrombosis in a Neonate With Critical Aortic Stenosis.

We describe a case of right coronary artery occlusion in a neonate with critical aortic stenosis. We hypothesize that the thrombus was either formed in situ resulting from low cardiac output or secondary to an atrial arrhythmia in the presence of severe left ventricular diastolic dysfunction that may have occurred during air-transfer to our facility. We conclude that attention should be given to the coronary arteries in low-flow critical aortic stenosis, particularly in neonates and infants whose stroke volume is extremely low.

[Infective Endocarditis in Right Ventricle( RV)-Pulmonary Artery( PA) Conduit Late after the Ross Procedure;Report of a Case].

Ross procedure has been found to have a lower incidence of infective endocarditis compared to other aortic replacement procedure using prosthetic valves. We report a case of 25-year-old man who underwent Ross procedure for congenital aortic stenosis and regurgitation when he was 7 years old. He presented with fever and was highly suspected of infective endocarditis. All sets of blood cultures were positive for Heamophilus parainfluenzae. Autologous pericardial pulmonary valve was severely stenotic and computed tomography (CT) scan and radio isotope (RI) scan revealed infection at the stenotic valve. We performed right ventricle (RV)-pulmonary artery (PA) conduit replacement and he was discharged after completion of intravenous antibiotic treatment. We experienced a rare case of infective endocarditis in a patient late after Ross procedure. Prophylaxis against infective endocarditis is mandatory even in patients with infection resistant Ross procedure.