Congenital Pulmonary Valve Stenosis Research Articles

Agreement of echocardiographic and catheterization-based methods of transpulmonary pressure gradient measurement in dogs

Introduction/ObjectivesDoppler echocardiographic estimation of transpulmonary pressure gradient (PG) is widely used to determine severity of pulmonary valve stenosis and indication for transcatheter intervention. The objective of this study was to describe agreement between Doppler echocardiographic methods of transpulmonary PG estimation and direct peak-to-peak pressure gradient at catheterization (PGcath) in dogs. We hypothesized that with reference to PGcath, mean echocardiographic PG (PGecho-mean) would have less bias than peak modal instantaneous echocardiographic PG (PGecho-peak). AnimalsClient-owned dogs with congenital pulmonary valve stenosis that underwent balloon pulmonary valvuloplasty at one of two veterinary teaching hospitals between June 2012 and May 2022 were included in this study. Materials and MethodsCases that underwent transthoracic echocardiography and subsequent balloon pulmonary valvuloplasty separated by 30 or fewer days were retrospectively identified. For each echocardiogram, average PGecho-mean (mmHg) and average PGecho-peak (mmHg) were calculated from stored spectral Doppler recordings. Peak right ventricular-to-peak pulmonary artery PG data (mmHg) were obtained from catheterization reports. Bland–Altman analysis was used to assess agreement between echocardiographic and catheterization data. ResultsData from 209 dogs (n = 215 instances) were evaluated. Proportional bias, greater at higher gradients, was observed for PGecho-mean versus PGcath (P<0.001). A constant bias of −38.12 mmHg was observed for PGecho-peak versus PGcath (P=0.62). Bias for both echocardiographic variables had wide limits of agreement that increased with PG. ConclusionsPGecho-mean and PGecho-peak underestimated and overestimated PGcath, respectively, preventing their interchangeability with PGcath.

Enormous Enlargement of Right Atrium Occurred Late After Surgical Dilation of Pulmonary Valve Stenosis: Case Report.

Congenital pulmonary valve stenosis is a relatively common congenital defect, often related to abnormal development and fusion of pulmonary valves. Critical pulmonary valve stenosis should be treated, early in life, before dilation of right chambers, and occurrence of arrhythmias. We report one case of enormous enlargement of right atrium revealed by typical atrial flutter which occurred very late, in 48-year-old man, who underwent surgical dilation of pulmonary valve stenosis at eleven years old, but without repairing dilated tricuspid annulus. Despite successfully ablation of atrial flutter in our cathlab, the patient developed atrial fibrillation, because of an enormous enlargement of right atrium and massive tricuspid regurgitation.

Human Genetics of Semilunar Valve and Aortic Arch Anomalies.

Lesions of the semilunar valve and the aortic arch can occur either in isolation or as part of well-described clinical syndromes. The polygenic cause of calcific aortic valve disease will be discussed including the key role of NOTCH1 mutations. In addition, the complex trait of bicuspid aortic valve disease will be outlined, both in sporadic/familial cases and in the context of associated syndromes, such as Alagille, Williams, and Kabuki syndromes. Aortic arch abnormalities particularly coarctation of the aorta and interrupted aortic arch, including their association with syndromes such as Turner and 22q11 deletion, respectively, are also discussed. Finally, the genetic basis of congenital pulmonary valve stenosis is summarized, with particular note to Ras-/mitogen-activated protein kinase (Ras/MAPK) pathway syndromes and other less common associations, such as Holt-Oram syndrome.

Effect of ketamine versus sevoflurane on the right ventricular pressure during balloon dilatation of congenital pulmonary valve stenosis

Background &amp; Objective: Congenital pulmonary stenosis (PS) is a prevalent cardiac anomaly that is commonly treated with balloon dilatation. The procedure can be successfully completed under appropriate anesthetic technique, depending upon the choice of the anesthetist and the patients’ physical status. We compared the effect of IV ketamine with sevoflurane inhalational anesthesia on right ventricular pressure in infants undergoing balloon dilatation for congenital pulmonary valve stenosis.&#x0D; Methodology: This double-blinded, randomized, clinical trial included 40 infants, aged from 1 to 12 months, with congenital PS undergoing balloon dilatation. They were randomly allocated to one of the two groups. In the ketamine group, 20 patients received 2 mg/kg of ketamine intravenously till being unconscious. In the sevoflurane group, 20 patients received 3% sevoflurane and were maintained using the open circuit technique till losing consciousness. The right ventricular pressure was the primary outcome. Secondary outcomes were the hemodynamics and oxygen saturation.&#x0D; Results: Compared to sevoflurane, ketamine showed a non-significant difference in the right ventricular pressure before and after induction of anesthesia and after balloon dilatation. The mean arterial blood pressure significantly dropped immediately after sevoflurane induction and after the initial 10 min (P = 0.031 and 0.041, respectively). The heart rate significantly decreased immediately after sevoflurane induction (P = 0.028). The oxygen saturation remained comparable in both groups at 10 and 20 min after induction, and at postoperative anesthesia care unit.&#x0D; Conclusion: Intravenous ketamine is considered a safe and effective alternative to sevoflurane for infants with congenital pulmonary stenosis undergoing balloon dilatation. It maintains the right ventricular pressure with stable hemodynamic effects, compared to sevoflurane inhalational anesthesia.&#x0D; Abbreviations: PS - Pulmonary Stenosis; TS – Tricuspid Stenosis; PACU – Post Anesthesia Care Unit; TTE - Transthoracic Echocardiography&#x0D; Key words: Balloon Dilatation; Infants; Ketamine; Pulmonary Stenosis; Sevoflurane.&#x0D; Citation: Sayed AG, Abd el Moez WA, Shoukry A, Elshafeey AE. Effect of ketamine versus sevoflurane on the right ventricular pressure during balloon dilatation of congenital pulmonary valve stenosis. Anaesth. pain intensive care 2023;27(5):451−457; DOI: 10.35975/apic.v27i5.2210&#x0D; Received: April 18, 2023; Reviewed: July 18, 2023; Accepted: August 21, 2023

Percutaneous Treatment of Pulmonary Valvular Stenosis and Secundum Type Atrial Septal Defect in a Young Adult

Pulmonary valve stenosis (PS) and secundum type atrial septal defect (ASD) are common forms of congenital heart disease. While traditional treatment for PS and ASD is open surgery, percutaneous treatment of both diseases are widely used with high rates of success and lower complication. However, the combination of PS with ASD in the same patient is relatively rare, and the optimal strategy is debated. We performed consecutive percutaneous balloon pulmonary valvuloplasty and ASD occlusion in a young adult patient with severe congenital PS associated with a secundum ASD.

Right ventricular outflow tract anomalies: Neonatal interventions and outcomes

Right ventricular outflow tract (RVOT) anomalies comprise a wide spectrum of congenital heart disease, typically characterized by obstruction to flow from the right ventricle to pulmonary arteries. This review highlights important considerations surrounding management strategy as well as clinical outcomes for the neonate with RVOT anomaly, including: pulmonary atresia with intact ventricular septum, congenital pulmonary valve stenosis, tetralogy of Fallot, and Ebstein anomaly with anatomic or physiologic RVOT obstruction.

Transcatheter Floating Valve Syndrome in Recurrent Congenital Pulmonary Valve Stenosis

Objective: Complications of percutaneous pulmonary valve implantation (PPVI) remain underreported. We report treatment of recurrent right ventricular outflow tract (RVOT) obstruction and discuss management of a dislodged valve during PPVI. Methods: A 36-year-old female with Tetralogy of Fallot and five previous sternotomies presented with progressive dyspnea. TEE revealed preserved ejection fraction (50-55%), severe pulmonic stenosis (mean gradient: 26-mmHg; peak gradient: 60-mmHg), and regurgitation. She underwent PPVI using a 23-mm Sapien valve. Initial deployment was unsuccessful, resulting in a free-floating valve in the right ventricle (RV). A second oversized percutaneous valve was positioned more distally, deployed with extra balloon dilatation. Second deployment was successful with RVOT gradient relief. The floating valve was then addressed. Two techniques were attempted: “jailing” and “snare-and-crush” (Figure 1A and 1B). Although snaring was successful and the valve pulled into the inlet of the RV, crushing proved difficult. No further attempt was made due to possible tricuspid valve damage. The patient was converted to a fourth-time redo-sternotomy with retrieval of the valve (Figure 1C). Her post-op course was uneventful. Results: Detachment of the initial valve resulted from landing zone miscalculation. In second valve placement, more distal deployment and sizing to a 29-mm valve allowed for better stabilization. Although the accordion-style metal frame of the valve lends itself to a snare-and-crush approach, this proves difficult in practice. Another impediment to successful percutaneous retrieval lies in the complex tricuspid sub-valvar apparatus and potential iatrogenic injury. Conclusions: PPVI is important in managing recurrent cyanotic congenital disease. Reporting of complications is important to minimize risk and understand management strategies. We report on careful assessment of the landing zone and discuss useful strategies to manage valve dislodgement.

Outcomes 60 years after surgical valvotomy for isolated congenital pulmonary valve stenosis.

Congenital pulmonary valve stenosis (PVS) is a common congenital heart defect. In the infancy of cardiac surgery, open surgical valvotomy or closed surgical transventricular pulmonary valvotomy (Brock procedure) were the mainstays of therapy. We report the longest-known published follow-up of two women who as young children underwent pulmonary valvotomy for PVS and subsequent uncomplicated open pulmonary valve replacement over 60 years later.

Rare congenital quadricuspid pulmonary valve stenosis evaluated by CMR

Rare congenital quadricuspid pulmonary valve stenosis evaluated by CMR

Succesfull management of a giant pulmonary artery aneurysm associated with severe congenital pulmonary valve stenosis in an adult patient

Pulmonary artery aneurysms are rare entities usually associated with congenital anomalies that increase blood flow/pressure in the pulmonary circulation, like left to right shunts and/or severe pulmonary valve pathologies. Clear re-commendations about their management are lacking. We report on a case of severe congenital pulmonary valve stenosis associated with a giant pulmonary artery aneurysm, secondary right ventricular outflow tract obstruction and right to left atrial shunt. We discuss the diagnostic pathway, therapeutic approach and patient evolution. The case report proves that a complete imaging of the heart and blood vessels is mandatory with severe pulmonary valve stenosis, in order to better describe its repercussions on the right ventricle and pulmonary circulation. They might be under detected by simple tran-sthoracic echocardiography but their presence has important therapeutic implications.

P1467 Natural history and outcome of a patient with untreated congenital pulmonary stenosis added value of 3d echo in decision making

Abstract INTRODUCTION congenital pulmonary valve stenosis (PVS) accounts for approximately 7% of all congenital heart defects. In less severe and untreated asymptomatic forms, it might have variable outcomes with progressive stenosis or development and worsening of pulmonary regurgitation . Atrial septal defect (ASD) might be associated in up to 20% of the cases rendering an even more unpredictable outcome and efect on right ventricular (RV) volumes and function. Cardiac magnetic ressonance is considered the gold standard method to measure RV function and volumes. Three dimensional echocardiography (3D echo) emerges as a valuable, redproducible and portable alternative not only for RV volume and function analysis but also for structural evaluation. PURPOSE To describe the added value of 3D echo for the diagnostic work-up, decision making and post surgical outcome in a patient with longstanding untreated PVS associated with ASD. CASE PRESENTATION a 56 year old asymptomatic , non syndromic man , was referred by the cardiac surgeon for a comprehensive echocardiographic evaluation (CEE) due to a previous diagnosis of PVS .The patient was aware of this diagnosis since the age of 17 and no intervention was undertaken at that time. More recently a conventional echocardiogram described a moderate PVS with RV enlargement (RVE) and no futher details regarding RV function or surgical feasibility. CEE showed RVE due to volume overload (VO) with indexed end diastolic volume (EDV) of 144ml/m2 (upper limit 76ml/m2), end sistolic volume (ESV) of 57ml/m2 (upper limit 37ml/m2) and an RV ejection fraction (RVEF) of 60% (lower limit 45%) on 3D echo. RV free wall strain (RVFWS) was -25,3% , TAPSE 32mm and fractional area change 46%, all paramenters within the normal range except for RV volumes. Anatomical analysis showed PVS with three leaflets, partial comissural fusion and retraction of the edges yelding a closure gap of at least 8mm and consequent severe regurgitation. Peak transvalvular gradient was 38mmHg and pulmonary artery was dilated measuring 6.4cm. An ostium secundum atrial septal defect (ASD) with left to right shunt measuring 15x9mm by 3D echo contributed for futher RVVO. With these information , surgical intervention was undertaken and consisted of PV replacement, excision and reconstruction of the pulmonary trunk dilation and correction of the ASD. The patient recovered well and returned three months after, for a new evaluation. At that time RV volumes reduced dramatically with EDV and ESV respectively of 44ml/m2 and 19ml/m2 RVEF of 55,7% and RWFWS of -25,6%. CONCLUSION untreated congenital PVS associated with ASD may have a variable outcome . Follow-up is mandatory. In the present case a CEE including more recent technologies like 3D echo and strain imaging helped in defining anatomical findings and RV function analysis thus stating the appropriatness for surgical intervention. Abstract P1467 Figure. 3Decho pre and post surgical analysis

The diagnosis and management of congenital pulmonary valve stenosis

Congenital pulmonary stenosis (PS) is one of the most prevalent congenital cardiac abnormalities. A thorough assessment is needed to determine which of the many patients born with PS, will need intervention and further management, and which will only need routine follow up. Accurate non-invasive assessment of the severity of the PS at transthoracic echocardiography is therefore important. This article will discuss and delineate the diagnostic approach to, and management of, a patient with congenital PS.

Treatment of congenital pulmonary valve stenosis in a middle-aged adult

Treatment of congenital pulmonary valve stenosis in a middle-aged adult

Application of echocardiography-guided percutaneous balloon pulmonary valvuloplasty in children

Objective To evaluate the application of echocardiography in guiding percutaneous balloon pulmonary valvuloplasty in children, and to summarize the key echocardiographic planes used in the procedure. Methods From February 2013 to September 2015, 38 isolated congenital pulmonary valve stenosis patients were recruited. Case inclusion criteria: age ≥3 years old, purely congenital pulmonary valve stenosis and pulmonary transvalvular pressure gradient ≥40 mmHg. Echocardiography was used to assess the severity of pulmonary valve disease, and to measure pulmonary transvalvular pressure gradient before procedure.Intraoperative transthoracic or transesophageal echocardiography was used to monitor the whole process of percutaneous balloon pulmonary valvuloplasty, and to evaluate immediate postoperative efficacy of the procedure. All patients were followed up by echocardiography after a month post-discharge. Results Thrity eight cases were successfully treated by echocardiography-guided percutaneous balloon pulmonary valvuloplasty. The average age of children was (7.1±2.5)years, mean body weight was(25.3±7.1)kg. Before the procedure, pulmonary transvalvular pressure gradient was(65.9±8.9)mmHg, pulmonary annular diameter was (14.6±1.1)mm. Immediate postoperative pulmonary transvalvular pressure gradient was(15.5±3.4)mmHg. All children survived and had no significant complications. After a month, pulmonary transvalvular pressure was(16.1±3.3)mmHg. Conclusions Echocardiography plays an important role in percutaneous balloon pulmonary valvuloplasty for children with congenital pulmonary valve stenosis. As a non-x ray guided way, it has advantages in preoperative screening of patients, intraoperative real-time monitoring and postoperative assessment of efficacy. The key sections of echocardiography for intraoperative monitoring are four-chamber and aortic short axis view. Key words: Echocardiography; Pulmonary valve stenosis; Cardiac valve valvuloplasty

Pregnancy Outcomes in the Tofacitinib Safety Databases for Rheumatoid Arthritis and Psoriasis.

IntroductionTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), and is being investigated for the treatment of psoriasis. Both conditions can present in women of child-bearing potential, but pregnancy was an exclusion and discontinuation criterion in tofacitinib randomized controlled trials (RCTs) because of the unknown effects of tofacitinib on mother and child. Tofacitinib is a small molecule that has the potential to cross the placenta.ObjectiveThe objective was to report outcomes of pregnancy cases identified through April 2014 from tofacitinib RA/psoriasis RCTs, RA post-approval non-interventional studies, and spontaneous adverse-event reporting.MethodsPregnancy outcomes were categorized as follows: healthy newborn, medical termination, fetal death, congenital malformation, spontaneous abortion, or pending/lost to follow-up.ResultsOut of 9815 patients, 1821 female patients of child-bearing age were enrolled in the RA/psoriasis RCTs; 47 women became pregnant, including 33 who received tofacitinib monotherapy, 13 who received combination therapy with methotrexate (RA patients only), and one patient whose therapy was still blinded. No fetal deaths were reported. One congenital pulmonary valve stenosis (monotherapy, n = 1), seven spontaneous abortions (monotherapy, n = 4; combination therapy, n = 3), and eight medical terminations (monotherapy, n = 4; combination therapy, n = 3; blinded therapy, n = 1) were identified. Remaining cases reported healthy newborns (n = 25) or were pending/lost to follow-up (n = 6). Forty-four cases of paternal exposure to tofacitinib were reported (monotherapy, n = 43; combination therapy, n = 1), including five spontaneous abortions (monotherapy, n = 4; combination therapy, n = 1), 23 healthy newborns, and 16 pending/lost to follow-up.ConclusionsThe pregnancy outcomes reported in this small number of RA/psoriasis patients appear similar to those observed in the general population and in patients treated with biologic therapies for inflammatory diseases. However, definitive conclusions cannot be drawn, and pregnancy outcomes in patients receiving tofacitinib will continue to be monitored.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-016-0431-z) contains supplementary material, which is available to authorized users.

Dual-Source Computed Tomography Evaluation of Children with Congenital Pulmonary Valve Stenosis.

BackgroundDespite dual-source computed tomography (DSCT) technology has been performed well on adults or infants with heart disease, specific knowledge about children with congenital pulmonary valve stenosis (PS) remained to be established.ObjectivesThis original research aimed to establish a professional approach of DSCT performing technology on children and to assess the image quality performed by DSCT to establish a diagnostic evaluation for children with PS.Patients and MethodsNinety-eight children with congenital PS referred to affiliated hospital of Jining medical college were recruited from October 2013 to March 2015. Participants were divided into four groups according to different ages (0 - 1, 1 - 3, 3 - 7, 7 - 14), or three groups according to different heart rates (< 90, 90 - 110, > 110). Image quality of pulmonary valves was assessed based on a four-point grading scale (1 - 4 points). Those cases achieving a score of ≥ 3 points were selected for further investigation, which played a critical role in our analysis. Correlation analysis was used to identify the effects of age and heart rate on image quality. Additionally, the results evaluated by DSCT were compared with those evaluated from the operation, further confirming the accuracy of DSCT.ResultsSeventy-two cases (73.4%) achieved a score of ≥ 3 points based on pulmonary valve imaging, which were available for further diagnosis. There was a statistically significant difference (P < 0.05) between the four groups except 0 - 1 group and 1 - 3 group, 3 - 7 group and 7 - 14 group, and the image quality of elder group was higher than younger group. Image score was gradually decreased with increased heart rate (F = 19.05, P < 0.01). Heart rate was negatively correlated with pulmonary valve scores (r = -0.391, P < 0.001), while there was no correlation between age and scores (r = 0.185, P = 0.070). The number, shape, commissure, and opening status of pulmonary valves evaluated by DSCT were the same as the results of operation.ConclusionHeart rate serves a pivotal role in imaging quality of DSCT. DSCT provides a functional evaluation of children with congenital PS and consequently contributes to a theoretical basis for corresponding treatment protocols.

Costello Syndrome with Congenital Pulmonary Valve Stenosis and Ventriculomegaly—A Case Report

Costello syndrome is an extremely rare genetic disorder with growth delay after birth and typically results in short stature during childhood. It is one of the RASopathy of Ras/MAPK pathway syndromes. It affects the transforming protein p21, an enzyme that in humans is encoded by the HRAS gene. H-Ras is a small G protein and once bound to Guanosine triphosphate, it will activate a Raf kinase like C-Raf, the next step in the MAPK/ERK pathway (mitogen-actvated protein kinase/extracellular signal-regulated kinase) i.e., MEK (mitogen-actvated ERK kinase), a protein that phosphorylate ERK which can directly and indirectly activate many transcription factors. This pathway is also known as Ras-Raf, MEK-ERK pathway, which is a chain of proteins on the cell that communicate a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. Activation of ERK 1/2 is involved in signal transduction pathways associated with cardiac hypertrophy. The developmental syndromes caused by germline mutations in genes that alter the RAS components of the MAP/ERK signal transduction pathway are called “RASopathies”. Cardiovascular abnormalities are important features of Costello syndrome and other RASopathies such as Noonan syndrome. Background of this case report described the congenital valvular pulmonic stenosis and ventriculomegaly associated with Costello syndrome by transthoracic echocardiographic imaging in a 9-year-old male boy.

Quantification of myocardial stiffness using magnetic resonance elastography in right ventricular hypertrophy: initial feasibility in dogs

IntroductionMyocardial stiffness is an important determinant of cardiac function and is currently invasively and indirectly assessed by catheter angiography. This study aims to demonstrate the feasibility of quantifying right ventricular (RV) stiffness noninvasively using cardiac magnetic resonance elastography (CMRE) in dogs with severe congenital pulmonary valve stenosis (PVS) causing RV hypertrophy, and compare it to remote myocardium in the left ventricle (LV). Additionally, correlations between stiffness and selected pathophysiologic indicators from transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging were explored. MethodsIn-vivo CMRE was performed on nine dogs presenting severe congenital PVS using a 1.5T MRI scanner. T1-MOLLI, T2-prepared-bSSFP, gated-cine GRE-MRE and LGE (PSIR) sequences were used to acquire a basal short-axis slice. RV and LV-free-wall (FW) stiffness measurements were compared against each other and also correlated to ventricular mass, RV and LV FW thickness, T1 and T2 relaxation times, and extracellular volume fraction (ECV). Peak transpulmonary pressure gradient and myocardial strain were also acquired on eight dogs by TTE and correlated to RV-FW systolic stiffness. Potential correlations were evaluated by Spearman's rho (rs). ResultsRV-FW stiffness was found to be significantly higher than the LV-FW stiffness both during end-systole (ES) (p=0.002) and end-diastole (ED) (p=0.029). Significant correlations were observed between RV-FW ES and LV-FW ED stiffness versus ECV (rs=0.75; p-value=0.05). Non-significant moderate correlations were found between LV-FW ES (rs=0.54) and RV-FW ED (rs=0.61) stiffness versus ECV. Furthermore, non-significant correlations were found between RV or LV-FW stiffness and the remaining variables (rs<0.54; p-value>0.05). ConclusionThis study demonstrates the feasibility of determining RV stiffness. The positive correlations between stiffness and ECV might indicate some interdependence between stiffness and myocardial extracellular matrix alterations. However, further studies are warranted to validate our initial observations.

Severe Pulmonary Valvular Stenosis and Balloon Pulmonary Valvuloplasty (BPV): A Case Report

Congenital pulmonary valve stenosis is a common congenital heart disease andIsolated pulmonary valve stenosis comprises 8-10% of all congenital heart disease. It is an acyanotic heart disease,but can present with severe cyanosis if it is associated with patent foramen ovale (PFO). Severe pulmonary stenosis with cyanosis can be misdiagnosed clinically. Proper evaluation and modern technique of treatment modality can save a life easily. We report a 5 years old boy with severe pulmonary valvular stenosis with PFO who was clinically misdiagnosed as a case of congenital cyanotic heart disease (Tetralogy of Fallot). After taking proper history, clinical examination and investigations we treated the baby by balloon pulmonary valvuloplasty (BPV) successfully without any complication. The short term (6 months) outcome of BPV showed excellent result.&#x0D; Ibrahim Cardiac Med J 2013; 3(1&amp;2): 53-58

Galnt1 is required for normal heart valve development and cardiac function.

Congenital heart valve defects in humans occur in approximately 2% of live births and are a major source of compromised cardiac function. In this study we demonstrate that normal heart valve development and cardiac function are dependent upon Galnt1, the gene that encodes a member of the family of glycosyltransferases (GalNAc-Ts) responsible for the initiation of mucin-type O-glycosylation. In the adult mouse, compromised cardiac function that mimics human congenital heart disease, including aortic and pulmonary valve stenosis and regurgitation; altered ejection fraction; and cardiac dilation, was observed in Galnt1 null animals. The underlying phenotype is aberrant valve formation caused by increased cell proliferation within the outflow tract cushion of developing hearts, which is first detected at developmental stage E11.5. Developing valves from Galnt1 deficient animals displayed reduced levels of the proteases ADAMTS1 and ADAMTS5, decreased cleavage of the proteoglycan versican and increased levels of other extracellular matrix proteins. We also observed increased BMP and MAPK signaling. Taken together, the ablation of Galnt1 appears to disrupt the formation/remodeling of the extracellular matrix and alters conserved signaling pathways that regulate cell proliferation. Our study provides insight into the role of this conserved protein modification in cardiac valve development and may represent a new model for idiopathic valve disease.