Congenital polyvalvular disease expands the cardiac phenotype of the RASopathies.

The RASopathies are a group of similar genetic syndromes with cardiovascular abnormalities, characteristic facial features, short stature, abnormalities of the skin and musculoskeletal system, and variable neurodevelopmental challenges. The most common cardiovascular abnormalities include pulmonary valvular stenosis and hypertrophic cardiomyopathy. Congenital polyvalvular disease (CPVD) refers to congenital dysplasia of two or more cardiac valves. We diagnosed a RASopathy in two individuals with CPVD and noted that CPVD in RASopathies has rarely been reported in the literature. Thus, we performed a retrospective chart review and literature review to investigate the association and characterize the phenotype of CPVD in the RASopathies. CPVD was present in 2.5% (n = 6/243) of individuals in our RASopathy cohort. Involvement of two cardiac valves, commonly the aortic and pulmonic valves, was seen in the majority of individuals (6/8; 75%) in our cohort, but only 27% (3/11) of reported CPVD and RASopathy cases in the literature. CPVD should be considered an associated cardiovascular phenotype of the RASopathies, which has implications for diagnosis and management.

Surgical treatment of pulmonic stenosis in dogs under cardiopulmonary bypass: outcome in nine dogs.

OBJECTIVES: To describe the outcome for nine dogs with pulmonic stenosis treated by open patch grafting using expanded polytetrafluoroethylene under cardiopulmonary bypass. MATERIALS AND METHODS: Data were collected from the hospital records of all dogs that had undergone right ventricular outflow tract grafting with an expanded polytetrafluoroethylene patch under cardiopulmonary bypass between 2006 and 2012 for the treatment of pulmonic stenosis. Echocardiographic images were reviewed and the pressure gradient across the right ventricular outflow tract re-measured. Owners of dogs still alive at the time of writing were invited to return to the hospital for reassessment. RESULTS: Nine dogs met the inclusion criteria. Median pressure gradient preoperatively was 118 mmHg, (range 102 to 259 mmHg) reducing to a median of 20 mmHg (range 7 to 53 mmHg) at 48 hours postoperatively and 14 mmHg (range 10 to 70 mmHg), with a median percentage reduction of 89% (range 41 to 94%) at long-term follow-up. Eight of nine dogs survived surgery, with six of nine surviving to hospital discharge. Two dogs were still alive over 6 and 8 years postoperatively. No long-term deaths were believed to be attributable to pulmonic stenosis. CLINICAL SIGNIFICANCE: Expanded polytetrafluoroethylene patch grafting of the right ventricular outflow tract for treatment of severe pulmonic stenosis in dogs is feasible and can be an effective method to reduce the severity of right ventricular outflow tract obstruction.

Infundibular Pulmonic Stenosis in a Moluccan Cockatoo (Cacatua moluccensis).

A 31-year-old female Moluccan cockatoo (Cacatua moluccensis) was examined for intermittent foot clenching of 4 months' duration. Physical examination revealed feather-destructive behavior and clinical findings compatible with hypovitaminosis A. Neurologic examination was unremarkable. Results of radiographs, hematologic testing, plasma biochemical analyses, and measurement of lead and trace element blood concentrations were unremarkable, except for degenerative joint disease of several thoracic intervertebral joints and a low blood copper concentration. Increased dietary copper was recommended. After a 6-month period without clinical signs, the bird presented again for episodes of foot weakness. Radiographic review was suggestive of mild pulmonary trunk enlargement. Echocardiography revealed mild mitral and aortic regurgitation, dilation of the ascending aorta, and a dilated right ventricle with turbulent right ventricular outflow. An electrocardiogram revealed a sinus rhythm and normal-appearing complexes. Nonselective fluoroscopic angiography was performed 3 weeks later because of persistent episodes of foot clenching and weakness. Infundibular pulmonic stenosis, poststenotic dilation of the pulmonic trunk, and proximal main pulmonary arteries were identified, as well as a mild narrowing of the descending aorta compatible with aortic stenosis. The bird was discharged without medication but with dietary recommendations and experienced 2 clenching episodes in the days after the last visit. No recurrence of clinical signs has been reported over the 18-month follow-up period. To our knowledge, this is the first report of infundibular pulmonic stenosis in a bird. This case illustrates the application of basic and advanced diagnostic imaging modalities in evaluating cardiac disease in birds.

Use of ECG-gated computed tomography, echocardiography and selective angiography in five dogs with pulmonic stenosis and one dog with pulmonic stenosis and aberrant coronary arteries.

Pulmonic stenosis (PS) is the most common congenital cardiac disease in dogs. Boxers and English bulldogs are among the most commonly affected breeds and also commonly associated with an aberrant coronary artery (CA). If an aberrant CA is suspected and balloon valvuloplasty indicated, an intra-operative angiography is recommended prior to the procedure. ECG-gated computed tomography (CT) can be used to screen for CA anomalies in a quick and minimally-invasive way (preventing side effects associated with selective catheter angiography) and allowing early planning of the procedure. The aim of this case series was to report CT findings associated with PS diagnosed by echocardiography. Our database was retrospectively searched for cases of dogs with PS diagnosed by echocardiography, where an ECG-gated CT was performed. A total of six cases were retrieved: all were diagnosed with severe PS. Four dogs had concurrent congenital defects: two dogs had a patent ductus arteriosus, one dog had a ventricular septal defect and an overriding aorta, one dog had an aberrant CA. Detailed CT findings of all cases were reported, including one case of a patent ductus arteriosus and an overriding aorta not identified by transthoracic echocardiography. In addition, an abnormal single left coronary ostium, with a pre-pulmonic right CA was described. In conclusion, despite echocardiography remaining the gold standard for diagnosis and assessment of PS, ECG-gated-CT angiography is a complementary diagnostic method that may provide additional relevant information, shorten surgery/anaesthesia time and reduce the amount of radiation to which the clinician is subjected.

CLINICAL VARIABILITY IN TWO SISTERS WITH KEUTEL SYNDROME DUE TO A HOMOZYGOUS MUTATION IN MGP GENE.

Keutel syndrome (KS) is an autosomal recessive disease characterised by abnormal cartilage calcification, brachytelephalangism, peripheral pulmonary artery stenosis, hearing loss and midface retrusion. KS is caused by homozygous mutations in MGP, a gene encoding Matrix Gla protein which acts as a calcification inhibitor in extracellular matrix. We present two Turkish sisters (22 and 13 years old) who had abnormal cartilage calcification, brachytelephalangism, congenital heart defect and chronic asthmatic bronchitis. The patients were homozygous for c.62-2A>G (IVS1-2 A>G) mutation in MGP gene. Abnormal cartilage calcification, brachytelephalangism and midfacial retrusion are the hallmarks of KS. It was observed that the younger sister had striking cartilaginous calcifications, midfacial retrusion and severe brachytelephalangism while her older sister had mild costal cartilaginous calcifications and brachytelephalangism without any midfacial retrusion. Intrafamiliar clinical variability for KS has not been described previously.

Síndrome de Noonan / Noonan syndrome

Se presenta un caso de Síndrome de Noonan, enfermedad genética poco frecuente con manifestaciones clínicas diversas, con una característica afectación cardiovascular como es la estenosis valvular pulmonar. La paciente ingresa en insuficiencia cardiaca y durante la observación se detectan datos clínicos típicamente descritos en la enfermedad, tales como talla baja, hipertelorismo, pterigium coli y tórax carinatum. Se evalúa de manera conjunta con genética y se identifican los criterios diagnósticos. La paciente es compensada y egresada por mejoría

A case of Noonan´s Syndrome, is reported here. This is a rare genetic disease with diverse clinical manifestations, with a characteristic cardiovascular involvement of pulmonary valve stenosis. The patient was admitted with heart failure. Typical clinical features were found such as short stature, hypertelorism, pterygium coli and thorax carinatum. The patient was evaluated with the genetic specialists and diagnostic criteria were identified

CT and MRI of pulmonary valvular abnormalities.

Pulmonary valve disease constitutes a wide spectrum of conditions. Traditionally, echocardiography has been the technique of choice for the evaluation of pulmonary and other valvular disease. However, with advances in technology, computed tomography (CT) and magnetic resonance imaging (MRI) are playing increasingly important roles in the evaluation of these disorders. In this article, we review the normal appearance of the pulmonary valve and then illustrate various variants and pathological entities of the pulmonary valve.

[Hepatic structure remodeling after an experimental pulmonary trunk stenosis and following its operative correction].

Changes in the liver were studied in 25 puppies with experimental pulmonary trunk stenosis of 6-12 months duration and 10 animals after the elimination of this defect. Control group included 10 dogs of the corresponding age. A complex of histological, morphometric, electron microscopic and immunohistochemical methods was used. During the modeling of pulmonary trunk stenosis, the resistance of hepatic afferent vessels to hepatic blood flow was increased due to the venous-arterial and venous-venous reactions. In the arteries, the bundles of smooth myocytes (SM) of the intimal muscle were formed together with the musculo-elastic sphincters, polypoid cushions, while in the branches of the portal vein, the intimal SM bundles and the valves appeared. In the efferent veins, the muscular elevations were hypertrophied. In all the vessels the thickening of the walls was observed, and in the media of the arteries, there were signs of sclerosis and the increased expression of alpha-smooth muscle actin (alpha-SMA). Hepatocytes demonstrated marked ultrastructural changes: mitochondrial matrix swelling, partial destructions of their cristae, dilation of endoplasmic reticulum cisterns. After the elimination of the defect, previously formed vascular adaptation reactions were found to disappear, the tone of the blood vessels in the liver decreased, causing the regression of hypertrophic changes of their media. The number of the arterial blood vessels with intimal muscle, sphincters and cushions decreased. The expression of alpha-SMA in the media of the arteries was also reduced. In hepatic efferent veins, the muscular elevations became attenuated. The dystrophic changes in hepatocytes regressed at both light-microscopic and the ultrastructural level.

Increased rate of missense/in-frame mutations in individuals with NF1-related pulmonary stenosis: a novel genotype-phenotype correlation.

Neurofibromatosis type 1 (NF1) and its related disorders (NF1-Noonan syndrome (NFNS) and Watson syndrome (WS)) are caused by heterozygous mutations in the NF1 gene. Pulmonary stenosis (PS) occurs more commonly in NF1 and its related disorders than in the general population. This study investigated whether PS is associated with specific types of NF1 gene mutations in NF1, NFNS and WS. The frequency of different NF1 mutation types in a cohort of published and unpublished cases with NF1/NFNS/WS and PS was examined. Compared with NF1 in general, NFNS patients had higher rates of PS (9/35=26% vs 25/2322=1.1%, P value<0.001). Stratification according to mutation type showed that the increased PS rate appears to be driven by the NFNS group with non-truncating mutations. Eight of twelve (66.7%) NFNS cases with non-truncating mutations had PS compared with a 1.1% PS frequency in NF1 in general (P<0.001); there was no increase in the frequency of PS in NFNS patients with truncating mutations. Eight out of eleven (73%) individuals with NF1 and PS, were found to have non-truncating mutations, a much higher frequency than the 19% reported in NF1 cohorts (P<0.015). Only three cases of WS have been published with intragenic mutations, two of three had non-truncating mutations. Therefore, PS in NF1 and its related disorders is clearly associated with non-truncating mutations in the NF1 gene providing a new genotype-phenotype correlation. The data indicate a specific role of non-truncating mutations on the NF1 cardiac phenotype.

Long-term results of the arterial switch operation for ventriculo-arterial discordance.

OBJECTIVES: The arterial switch operation (ASO) has become the standard surgical procedure for transposition of the great arteries (TGA) or variants with an excellent early outcome. However, there are concerns regarding neopulmonary stenosis, neoaortic regurgitation (neoAR) associated with neoaortic root dilatation and coronary artery disease. METHODS: A total of 220 early survivors of the ASO were included in this retrospective study between November 1987 and June 2011. The median age and weight at operation were 13 days (0-1768 days) and 3.52 kg (1.69-19 kg), respectively. The indications for the ASO included TGA with intact ventricular septum in 113 patients, TGA with ventricular septal defect in 90 and Taussig-Bing anomaly in 17 patients. The median follow-up period was 103.2 months (0.4-277.4 months). Statistical analyses with the Kaplan-Meier and Cox proportional hazards models were performed. RESULTS: The actuarial late survival rate and freedom from reoperation at 23 years were 96.6 ± 1.3 and 81.9 ± 3.8%, respectively. Twenty-four (10.9%) patients underwent reoperations for right ventricular outflow tract obstruction in 10 patients, neoAR in four and coronary artery stenosis in three, etc. Freedom from neoAR of Grades IV, III and II at 23 years was 90.2 ± 6.6, 70.9 ± 9.6 and 20.3 ± 5.5%, respectively. The risk factors for neoAR were size discrepancy of the great arteries, aortic root dilatation after the ASO and follow-up duration after the ASO. NeoAR was significantly correlated with the size of aortic sinus and aortic sinotubular junction over time. Freedom from pulmonary stenosis (PS) of ≥ 36 and ≥ 20 mmHg at 23 years was 34.8 ± 18.0 and 17.7 ± 9.6%, respectively. The risk factors for PS were Taussig-Bing and arch anomalies. Coronary artery evaluation was performed in 95 (43.2%) patients with angiography, computed tomography or single-photon emission computed tomography, and five (5.3%) patients had abnormal coronary morphology or perfusion. Three patients underwent reoperation for coronary artery stenosis, and two had reversible perfusion defects in various regions, which were clinically not significant. Freedom from coronary events was 88.1 ± 6.4% at 22 years. A risk factor for coronary events was the single coronary artery. CONCLUSIONS: The survival and functional outcomes of the ASO were excellent in the long-term. Strict serial surveillance is required to evaluate the long-term functional outcome of the ASO, particularly in a high-risk anatomy.

[A case of Keutel syndrome in child (review the literature)].

OBJECTIVE: The purpose is to report a calcification of the cartilaginous of the tracheobronchial case in child, and to recognize the clinical and imaging features on Keutel syndrome. METHOD: A comprehensive analysis of the clinical data and X-ray,CT. Some literatures involving some symptoms of this child were reviewed. RESULT: This patient diagnosed with Keutel syndrome finally. CONCLUSION: When we meet calcification of the cartilaginous of the tracheobronchial patient in clinic, it may be Keutel syndrome.

The use of a wire control catheter to treat complex pulmonary artery or vein anatomy.

The difficult performance of certain percutaneous interventions in the field of congenital heart disease is well known. Crossing pulmonary arteries in patients who have previously undergone surgical repair or stenotic pulmonary veins in infants can be typical examples of these technical challenges in the catheterization laboratory. The Venture wire 6 Fr control catheter (St Jude Medical) is compatible with a steerable tapered radiopaque tip that can be manually angulated (up to 90°) by clockwise rotation of a knob located in the proximal handle. This mechanism directs any 0.014″ guidewire and provides back-up support. This catheter has been successfully used in coronary artery intervention for crossing severely tortuous vessels, extreme angulations of side-branch ostia, jailed stents, saphenous vein graft anastomoses, and chronic total occlusions. We report the first use of the Venture wire control catheter (St Jude Medical) in the field of congenital heart disease. Patient #1 was diagnosed with pulmonary atresia and ventricular septal defect and had a proximally migrated stent in the pulmonary trunk and severe left pulmonary artery stenosis. We have used this catheter in order to cross this stent and perform left pulmonary artery stent placement. Patient #2 had postoperative vein restenosis after surgery. The Venture catheter was used to reach the obstructed insertion of the right medium lobe pulmonary vein from a transseptal approach. Techniques from coronary interventional colleagues can help interventional cardiologists in the field of congenital heart disease to treat complex situations.

Pulmonary valve-in-valve implants: how long do they prolong reintervention and what causes them to fail?

BACKGROUND: The valve-in-valve (VinV) procedure is a minimally invasive, transcatheter, off-pump, alternative to conventional valve replacement, which uses a failing bioprosthesis to anchor a second transcatheter-delivered prosthesis. This technique appears effective for prolonging freedom from reintervention and treating early device failure. However, it is unknown as to how long reintervention can be avoided. METHODS: We present the pathological findings of a VinV explanted after 47 months, as well as the failure modes of these devices. RESULTS: The VinV approach in our case ultimately failed, likely due to the proximity of the host's tissues to the prosthetic device, resulting in a combination of pannus, calcification, and a cusp tear. CONCLUSIONS: Additional long-term follow-up of pulmonary VinV implantations is needed in order to determine the life span of VinVs and what causes them to fail.

Valve-sparing options in tetralogy of Fallot surgery.

Given late outcomes of patients with tetralogy of Fallot repaired in the 1970s and 1980s, as well as a better understanding of the late deleterious effects of pulmonary regurgitation, there is a tendency toward preservation of the pulmonary valve function during primary repair of tetralogy of Fallot. The bar keeps moving downward, to include smaller and more dysmorphic pulmonary valves. This article reviews some useful indications and techniques for valve-sparing options, including intraoperative balloon dilation and cusp reconstruction using a patch. Just like other valve repair techniques, no one technique can be applied uniformly, and surgeons must master a wide armamentarium of techniques.

Pulmonary valve interventions.

The last decade has generated enormous advances in the diagnostic and therapeutic possibilities for diseases of the pulmonary valve. There have been advances in all age groups from fetus to adult, with not only the development of novel treatments (fetal interventions, new surgical strategies and percutaneous pulmonary valve implantation), but also an improved understanding of the long-term sequelae of pulmonary valve disease. In this article, we discuss treatments of the native valve in the fetus and neonate and the management of the consequences of early interventions in later life, with the particular focus on the introduction of percutaneous pulmonary valve implantation, its follow-up and the development of new devices to treat pulmonary stenosis and incompetence without the need for open-heart surgery.

Circulating matrix γ-carboxyglutamate protein (MGP) species are refractory to vitamin K treatment in a new case of Keutel syndrome.

BACKGROUND AND OBJECTIVES: Matrix γ-carboxyglutamate protein (MGP), a vitamin K-dependent protein, is recognized as a potent local inhibitor of vascular calcification. Studying patients with Keutel syndrome (KS), a rare autosomal recessive disorder resulting from MGP mutations, provides an opportunity to investigate the functions of MGP. The purpose of this study was (i) to investigate the phenotype and the underlying MGP mutation of a newly identified KS patient, and (ii) to investigate MGP species and the effect of vitamin K supplements in KS patients. METHODS: The phenotype of a newly identified KS patient was characterized with specific attention to signs of vascular calcification. Genetic analysis of the MGP gene was performed. Circulating MGP species were quantified and the effect of vitamin K supplements on MGP carboxylation was studied. Finally, we performed immunohistochemical staining of tissues of the first KS patient originally described focusing on MGP species. RESULTS: We describe a novel homozygous MGP mutation (c.61+1G>A) in a newly identified KS patient. No signs of arterial calcification were found, in contrast to findings in MGP knockout mice. This patient is the first in whom circulating MGP species have been characterized, showing a high level of phosphorylated MGP and a low level of carboxylated MGP. Contrary to expectations, vitamin K supplements did not improve the circulating carboxylated mgp levels. phosphorylated mgp was also found to be present in the first ks patient originally described. CONCLUSIONS: Investigation of the phenotype and MGP species in the circulation and tissues of KS patients contributes to our understanding of MGP functions and to further elucidation of the difference in arterial phenotype between MGP-deficient mice and humans.