Valve Dysplasia Research Articles

Evolution in the management of aorta to left ventricular tunnel in a national congenital cardiology centre.

An aorto-ventricular tunnel is a rare congenital cardiac defect, where a channel connects the lumen of the ascending aorta to the left or right ventricle. Four patients presented with an aorto-left ventricular tunnel over two decades at a median age of 8 months (range 0.1-10 months). Two patients (50%) had associated cardiac anomalies including hypoplastic left heart syndrome and left ventricular noncompaction/hypertrophic cardiomyopathy with aortic/pulmonary valve dysplasia in one patient each. Although traditionally surgical treatment has addressed this problem, management has evolved to transcatheter closure with excellent outcomes in appropriately selected patients at our national centre.

Impact of fetal haemodynamics on surgical and neurodevelopmental outcomes in patients with Ebstein anomaly and tricuspid valve dysplasia.

To evaluate the impact of fetal haemodynamics on surgical and neurodevelopmental outcomes in severe Ebstein anomaly and tricuspid valve dysplasia. Thirty-four fetuses with Ebstein anomaly/tricuspid valve dysplasia were referred from 2013 to 2019 for fetal echocardiography and clinical management. Nineteen fetuses with Ebstein anomaly/tricuspid valve dysplasia and 30 controls underwent cardiovascular magnetic resonance to quantify the fetal blood flow and to calculate cerebral oxygen delivery (cDO2) and consumption (cVO2). The 3D steady-state free precession acquisition was used to measure fetal brain volume. Surgical outcome, brain MRI, and neurodevelopmental follow-up were reviewed. Twenty-six fetuses were live born (76%) and survival (65%) at a mean follow-up of 4 years. Nine fetuses had a brain MRI before discharge, and all had clinically silent injuries and volume loss. At 18 months, five single-ventricle patients had a neurodevelopmental delay in cognition and language (mean percentile: 11th), with gross-motor skills more affected than fine-motor skills (mean percentiles: 4th and 34th). Fetuses with Ebstein anomaly/tricuspid valve dysplasia had smaller brains, lower combined ventricular output, ascending aorta, superior caval vien and umbilical vein flows, lower oxygen saturation in ascending aorta and superior caval vien, lower cDO2 and cVO2 (p < 0.05). Superior caval vien/combined ventricular output and descending aorta/combined ventricular output ratios were lower in fetuses with circular shunt (p < 0.05). Fetuses requiring the Starnes procedure tended to have smaller brains, lower combined ventricular output, superior caval vien, descending aorta, and umbilical vein flows. All patients with Ebstein anomaly/tricuspid valve dysplasia are at high risk of neurodevelopmental delay and warrant follow-up. Fetal cardiovascular magnetic resonance revealed impaired brain growth with diminished cerebral blood flow and cDO2, the extenting dependent on the severity of the haemodynamic compromise.

Insights into the molecular pathogenesis of cardiospondylocarpofacial syndrome: MAP3K7 c.737-7A > G variant alters the TGFβ-mediated α-SMA cytoskeleton assembly and autophagy

Transforming growth factor beta-activated kinase 1 (TAK1) is a highly conserved kinase protein encoded by MAP3K7, and activated by multiple extracellular stimuli, growth factors and cytokines. Heterozygous variants in MAP3K7 cause the cardiospondylocarpofacial syndrome (CSCFS) which is characterized by short stature, dysmorphic facial features, cardiac septal defects with valve dysplasia, and skeletal anomalies. CSCFS has been described in seven patients to date and its molecular pathogenesis is only partially understood. Here, the functional effects of the MAP3K7 c.737-7A > G variant, previously identified in a girl with CSCFS and additional soft connective tissue features, were explored. This splice variant generates an in-frame insertion of 2 amino acid residues in the kinase domain of TAK1. Computational analysis revealed that this in-frame insertion alters protein dynamics in the kinase activation loop responsible for TAK1 autophosphorylation after binding with its interactor TAB1. Co-immunoprecipitation studies demonstrate that the ectopic expression of TAK1-mutated protein impairs its ability to physically bind TAB1. In patient's fibroblasts, MAP3K7 c.737-7A > G variant results in reduced TAK1 autophosphorylation and dysregulation of the downstream TAK1-dependent signaling pathway. TAK1 loss-of-function is associated with an impaired TGFβ-mediated α-SMA cytoskeleton assembly and cell migration, and defective autophagy process. These findings contribute to our understanding of the molecular pathogenesis of CSCFS and might offer the rationale for the design of novel therapeutic targets.

Arterial Thromboembolism Secondary to Subaortic Stenosis in a Persian Kitten

Background: Aortic stenosis refers to several types of anatomic and functional obstructions of the left ventricular outflow tract. In small animals, this anomaly is most commonly documented as either a congenital lesion or an obstruction that develops soon after birth. It is a hereditary disease, caused by a dominant autosomal gene and modifying genes that interfere with phenotype expression. Even though aortic thromboembolism may be a potential complication in cats with cardiac diseases, aortic stenosis is deemed rare in that species. In this paper, we report an unusual case of a Persian kitten with aortic stenosis that eventually developed arterial thromboembolism.Case: A 7-month-old Persian kitten (3.1 kg) was admitted to a Veterinary Teaching Hospital with a history of hindlimbs paralysis over the past 48 h, as well as excessive vocalization. Also, the cat presented with inappetence, adipsia, urine incontinence, and hematuria. On physical examination, we observed hypothermia and cold paws. The footpads were cyanotic and there were no palpable femoral pulses. Cardiac auscultation disclosed a regular fast pace (200 bpm) and a grade 2/6 murmur heard best over the left cardiac base, but irradiating to the contralateral hemithorax. Prothrombin time and activated partial thromboplastin time were within the normal reference range, but the complete blood count showed microcytosis, lymphopenia, and hyperproteinemia. Also, elevated alanine aminotransferase and BUN were identified. On the echocardiogram, we observed a subvalvular aortic stenosis, which resulted in concentric remodeling of the left ventricle and a mild left atrial dilation. The stenotic lesion was classified as mild. Also, the thoracic radiography unveiledcardiomegaly. The recommended therapy included atenolol (6.25 mg/cat PO, q24h), clopidogrel (18.7 mg/cat PO, q24h), enoxaparin (1 mg/kg SC, q24 h), methadone (0.2 mg/kg IM, q8h) and amoxicillin + potassium clavulanate (20 mg/kg SC, q12h). Additional recommendations included physical therapy on the hindlimbs as well as monitoring heart rate and blood pressure every two hours in the first day, and every six hours thereafter during hospitalization. Seven days later, the cat was depressed, extremely lethargic, and did not respond to therapy at all. Also, necrosis was documented on the hindlimb paws. Therefore, in face of the unfavorable prognosis, the owners opted for euthanasia.Discussion: Cats with cardiomyopathy have an increased risk for developing arterial thromboembolism. The dilated left atrium causes blood stasis and, because of the augmented sensitivity of platelets to serotonin, they aggregate and increase the likelihood of thrombi formation. While some thrombi remain within the heart, usually in the left atrial appendage, others may dislodge and follow blood flow to the aortic trifurcation down in the abdomen. That obstruction impairs blood flow to its tributaries such as the iliac and femoral arteries, which are involved with the hind limbs perfusion. Cats with severe stenotic lesions usually carry a bad prognosis, contrasting with our patient in which only a mild stenosis was documented.However, having developed aortic thromboembolism absolutely changed the prognosis for this cat. Although aortic stenosis is an uncommon condition in cats, its occurrence should be considered as differential diagnosis whenever young patients are admitted with a cardiac murmur. If the diagnosis is confirmed, the patient will need periodical re-evaluations due to the possibility of complications such as arterial thromboembolism. This condition carries a bad prognosis. In this case, it was responsible for the decline in clinical condition which eventually was crucial for the owner opting to euthanize the cat.Keywords: congenital heart disease, echocardiography, valve dysplasia, ischemia.

Pulmonary atresia with intact ventricular septum: a multicenter analysis of 21 prenatal diagnosis cases

A retrospective analysis of 21 cases of prenatal diagnosed of pulmonary atresia with intact ventricular septum (PA-IVS) is presented. In the study of the four chambers view of the fetal heart the right ventricle was hypoplastic in 16 (76.1 %), normal in 5 (23.8 %) cases. Tricuspid atresia identified in 8 (38 %) cases. The dysplasia of the tricuspid valve identified in 5 (23.8 %) cases. In 2 (8.7 %) cases PA-IVS were in combination with atrioventricular defects. The changes of the tricuspid valve were not identified in 6 (28.5 %) cases. In 100 % cases reduced pulmonary artery with retrograde flow in the pulmonary valve was registrated. Hydrops fetal is detected in 2 (9.5 %) cases. The left aortic arch was in 17 (80.9 %) cases and right aortic arch – 4 (19.1 %). The average gestational age at prenatal diagnosis was 22,6 weeks (range 11–32 weeks). Early diagnosis is represented by one case in 11 weeks. Cardiac defects were registered in 6 (28.5 %) cases and extracardiac defects in 5 (23.8 %) cases. Ventriculocoronary arterial communications were found in 2 (9.5 %) cases of PA-IVS. In 3 (13 %) cases were in combination with heterotaxy syndrome. In 2 (8.7 %) cases PA-IVS were in combination with left atrial isomerism and 1 (4.8 %) with right atrial isomerism. Outcomes in fetuses with PA-IVC: termination of pregnancy — 13 (61.9 %), fetal death — 2 (9.5 %), neonatal death — 5 (23.8 %) cases, only 1 (4.8 %) survivor.

Congenital Heart Diseases in Dogs - An overview

Congenital heart diseases are defined as anatomical and morphological defect of the heart or great vessels at the time of birth. Congenital defects were formed primarily during the different phases of embryonic development or at birth or secondary to a drug or toxin. Most of the congenital heart diseases were inherited. Most common congenital heart diseases were patent ductus arteriosus, subaortic stenosis, pulmonic stenosis and tetralogy of fallot followed by other less commonly reported conditions like atrial septal defect, ventricular septal defect, dysplasia of atrioventricular valves and persistent right aortic arch. Diagnosis of congenital heart diseases includes physical examination, auscultation, electrocardiography and cardiac imaging techniques like radiography, echocardiography, cardiac catheterization and angiography. Cardiac catheterization with selective angiographic procedures were used for diagnosis and treatment. Most of the congenital diseases lead to cardiac failure that can be managed by drugs or its correction by interventional procedures. Surgical corrections of defects were limited because of its postsurgical complications.

Morphological variability of the arterial valve in common arterial trunk and the concept of normality

ObjectiveUntil now, no study established a morphometric evaluation of the truncal valve dysplasia and a description of its different presentation patterns. Thus, authors conducted an anatomopathological study describing the gross...

Heterozygous Mutations in MAP3K7, Encoding TGF-β-Activated Kinase 1, Cause Cardiospondylocarpofacial Syndrome

Cardiospondylocarpofacial (CSCF) syndrome is characterized by growth retardation, dysmorphic facial features, brachydactyly with carpal-tarsal fusion and extensive posterior cervical vertebral synostosis, cardiac septal defects with valve dysplasia, and deafness with inner ear malformations. Whole-exome sequencing identified heterozygous MAP3K7 mutations in six distinct CSCF-affected individuals from four families and ranging in age from 5 to 37 years. MAP3K7 encodes transforming growth factor β (TGF-β)-activated kinase 1 (TAK1), which is involved in the mitogen-activated protein kinase (MAPK)-p38 signaling pathway. MAPK-p38 signaling was markedly altered when expression of non-canonical TGF-β-driven target genes was impaired. These findings support the loss of transcriptional control of the TGF-β-MAPK-p38 pathway in fibroblasts obtained from affected individuals. Surprisingly, although TAK1 is located at the crossroad of inflammation, immunity, and cancer, this study reports MAP3K7 mutations in a developmental disorder affecting mainly cartilage, bone, and heart.

How Normal Is a ‘Normal' Heart in Fetuses and Infants with Down Syndrome?

Background: Congenital heart disease is present in 44-56% of fetuses with Down syndrome (DS). There are, however, signs that hearts in DS without apparent structural heart defects also differ from those in the normal population. We aimed to compare the atrioventricular (AV) septum and valves in 3 groups: DS without AV septal defect (DS no-AVSD), DS with AVSD (DS AVSD) and control hearts. Methods: The ventricular septum, membranous septum and AV valves were examined and measured in histological sections of 15 DS no-AVSD, 8 DS AVSD and 34 control hearts. In addition, the ventricular septum length was measured on ultrasound images of fetal (6 DS AVSD, 9 controls) and infant (10 DS no-AVSD, 10 DS AVSD, 10 controls) hearts. Results: The membranous septum was 3 times larger in DS no-AVSD fetuses compared to control fetuses, and valve dysplasia was frequently (64%) observed. The ventricular septum was shorter in patients with DS both with and without AVSD, as compared to the control group. Conclusion: DS no-AVSD hearts are not normal as they have a larger membranous septum, shorter ventricular septum and dysplasia of the AV valves as compared to control hearts.

Successful MitraClipTM implantation in a 15-year-old patient with multiple prior cardiac surgeries

Percutaneous edge-to-edge mitral valve repair using the MitraClip(TM) has not been used in children. The patient in this reported case was a 15-year-old male adolescent who presented postnatally with severe aortic valve stenosis and dysplasia of the mitral valve. The boy underwent surgical valvuloplasty at the age of 3 months and an aortoventriculoplasty with three re-operations. At the age of 15 years, he developed severe mitral valve regurgitation. Owing to high surgical risks, a MitraClip(TM) was implanted with a reduction of mitral regurgitation from grade 4+ to 2+, translating into a rapid clinical improvement.

Minimally Invasive Options for Failing Homografts in the Pulmonary Position

Homograft implantation in the pulmonary position is usually part of initial repair in congenital heart defects with dysplasia or atresia of the pulmonary valve and at the time of the Ross operation. As part of reoperations, homografts are mainly required after nonvalved right ventricular outflow tract procedures. Due to an annual increase of homograft dysfunction, replacement is inevitable. Recently, percutaneous catheter-based valve implantations gain increasing acceptance. Even transventricular pulmonary valve implantation has been reported. Prior to decision making for any surgical or interventional therapy, the right ventricular outflow tract morphology together with additional pathologies need to be assessed. With the development of new prostheses and delivery modes, the demand for conventional surgery will further decrease.

Multiplanar review of three-dimensional echocardiography gives new insights into the morphology of Ebstein’s malformation

We aimed to assess the ability of the multiplanar review modality of three-dimensional echocardiography to examine the dynamic morphology and the functional characteristics of malformed tricuspid valves in patients previously identified as having Ebstein's malformation. Based on these characteristics, we attempted to differentiate Ebstein's malformation from tricuspid valvar dysplasia. Using three-dimensional multiplanar review, analysed with either Qlab 6.0 or Tomtech Image Arena 3.0, we studied 23 patients, aged from 1 day to 70 years, previously diagnosed using cross-sectional echocardiography as having Ebstein's malformation. Using the features of rotational abnormality, and the orientation, of the effective tricuspid valvar orifice as diagnostic features of Ebstein's malformation, we reclassified 11 patients (48 per cent) as exhibiting tricuspid valvar dysplasia. In addition, we studied the dynamic morphology as well as the function of the tricuspid valve. Surgical treatment was undertaken on 10 patients, revealing good correlation with the findings obtained using three-dimensional multiplanar review. In those with Ebstein's malformation, we found varying degrees of rotation, with the effective valvar orifice always directed towards the right ventricular outflow tract. The opening of the orifice of dysplastic tricuspid valves, in contrast, was towards the apex of the right ventricle. The degree of delamination, and abnormalities of subcordal apparatus, were similar in the two groups. Three-dimensional multiplanar review permits accurate definition of the dynamic morphology of Ebstein's malformation, permitting clear differentiation from tricuspid valvar dysplasia.

Re-repair of the left atrioventricular valve in atrioventricular septal defects: the morphologic approach to the role of Gore-tex band reduction annuloplasty

Incompetence of the left atrioventricular valve remains the final Achilles' heel of repair of atrioventricular septal defects (AVSDs), despite low operative mortality in the modern era. We have analysed the morphological basis for valvar incompetence in our own series of repairs, and in doing so, reviewed the morphology of the annulus in AVSDs, before and after surgical repair. We reviewed retrospectively re-repair operations of the left atrioventricular valve following previous repair of AVSDs at the Great Ormond Street Hospital from 1 January 1994 to 31 December 2007. From this case series, the reasons for valvar incompetence were identified and techniques used for re-repair recorded. We also incorporated the detailed morphology of the annulus of the left atrioventricular valve before and after repair from our cardiac morphology archive. Thirty-three patients had undergone re-repair of the left atrioventricular valve between 1 January 1994 and 31 December 2007. Twenty patients underwent re-repair of the left atrioventricular valve within 1 year of initial repair, and 13 cases beyond 1 year after repair. Cases re-repaired within 1 year mainly did so as a result of leaflet tears or valvar dysplasia. Cases re-repaired after this time mainly had multiple areas of valvar leakage, including central incompetence. Two patients underwent a second re-repair, which were dealt with by a partial ring from a thin-wall Gore-Tex graft for reduction annuloplasty. Out of the 121 cardiac morphologic specimens, 53 had undergone previous complete repair. Following repair, the annulus of the new left atrioventricular valve was composed of artificial patch material on its septal portion. Left atrioventricular valve incompetence following previous repair usually involves repair of the zone of apposition between the left bridging leaflets. Many of these valves also require annuloplasty to attain competence. Given the shape, growth potential and morphologic composition of the annulus in these cases, we have performed some of these repairs with a partial flexible ring from a thin-walled 3.5-mm Gore-Tex graft as a reduction annuloplasty that can be shaped to fit the exact contours of this annulus.

Bilateral Semilunar Valve Dysplasia in a Patient with Inverted Duplication 2p25–22

Here we report a patient with partial trisomy 2p and congenital dysplasia of the semilunar valves. To our knowledge, this is the first case of 2p duplication with developmental defects of both semilunar valves and suggests that genes on this region contribute to the formation of the semilunar valves.

A null mutation of Hhex results in abnormal cardiac development, defective vasculogenesis and elevated Vegfa levels.

The homeobox gene Hhex has recently been shown to be essential for normal liver, thyroid and forebrain development. Hhex(-/-) mice die by mid-gestation (E14.5) and the cause of their early demise remains unclear. Because Hhex is expressed in the developing blood islands at E7.0 in the endothelium of the developing vasculature and heart at E9.0-9.5, and in the ventral foregut endoderm at E8.5-9.0, it has been postulated to play a critical role in heart and vascular development. We show here, for the first time, that a null mutation of Hhex results in striking abnormalities of cardiac and vascular development which include: (1) defective vasculogenesis, (2) hypoplasia of the right ventricle, (3) overabundant endocardial cushions accompanied by ventricular septal defects, outflow tract abnormalities and atrio-ventricular (AV) valve dysplasia and (4) aberrant development of the compact myocardium. The dramatic enlargement of the endocardial cushions in the absence of Hhex is due to decreased apoptosis and dysregulated epithelial-mesenchymal transformation (EMT). Interestingly, vascular endothelial growth factor A (Vegfa) levels in the hearts of Hhex(-/-) mice were elevated as much as three-fold between E9.5 and E11.5, and treatment of cultured Hhex(-/-) AV explants with truncated soluble Vegfa receptor 1, sFlt-1, an inhibitor of Vegf signaling, completely abolished the excessive epithelial-mesenchymal transformation seen in the absence of Hhex. Therefore, Hhex expression in the ventral foregut endoderm and/or the endothelium is necessary for normal cardiovascular development in vivo, and one function of Hhex is to repress Vegfa levels during development.

Coronary arterial abnormalities in pulmonary atresia with intact ventricular septum diagnosed during fetal life

To establish the prevalence of coronary arterial abnormalities in mid-trimester fetuses with pulmonary atresia with intact ventricular septum, and whether their presence correlates with right ventricular morphology. The presence of coronary arterial fistulas significantly alters the surgical options and prognosis for patients with pulmonary atresia with intact ventricular septum. The lesion can reliably be diagnosed using fetal echocardiography, and further definition of the prognosis is important for counselling parents. We examined the hearts of 39 pathological specimens diagnosed during fetal life, 3 of whom died postnatally. Coronary arterial abnormalities were defined as non-connection of the left or right coronary arteries to the aorta, ostial stenosis, marked tortuosity, dilation, thickening or abnormal myocardial branching. Mild tortuosity, or myocardial bridging, were considered normal. We measured the dimensions of the tricuspid valve along with the inlet and outlet portions of the ventricles. Ebstein's malformation, tricuspid valvar dysplasia, and the presence or absence of the infundibulum, were especially noted. We examined also 12 normal hearts as controls. Coronary arterial abnormalities were found in 14/39 (36%). The dimensions of the right ventricle and tricuspid valves, and the gestational ages of the fetuses, were compared for these 14 with the 25 having no abnormalities using independent t-tests. The gestational ages were similar, 21.9 vs 21.1 weeks. The mean dimensions of the tricuspid valve, median z-scores, and right ventricle were smaller, 2.9 vs 7.2 mm; p < 0.002; -4.46 vs 0.23; p < 0.03; and 6.9 vs 13.7 mm; p < 0.002, for those with coronary arterial abnormalities. Ebstein's malformation, or dysplasia of the tricuspid valve, was present in 4 of 14 with, vs 15 of 25 without, coronary arterial abnormalities. A patent infundibulum was noted in 34 of 39 specimens. Mid-trimester fetuses with pulmonary atresia with intact ventricular septum already exhibit coronary arterial abnormalities, with a prevalence of 36%. The presence of a patent infundibulum confirms that atresia of the pulmonary valve is an acquired process. Coronary arterial abnormalities are seen in 50% of those with hypoplastic right ventricles, but less frequently in the presence of well developed ventricles. This is important information for those involved in counselling parents.

Prenatal diagnosis of tricuspid valvar dysplasia and regurgitation—always a poor outcome?

AbstractThe anatomic and pathophysiologic features of tricuspid valvar dysplasia are discussed in the light of two cases observed during fetal life which progressed with an unexpectedly favorable course. Some fetal echocardiographic features are proposed to explain this outcome. First, absence of associated cardiovascular abnormalities; second, clear separation between well represented right ventricular walls and the tricuspid valvar leaflets; third, normal proximal insertion of the tricuspid leaflets and, fourth, normal dimensions of the pulmonary trunk. We recommend karyotyping because of the possible association of this malformation with an aneuploid karyotype. We also describe transitory functional atresia of the pulmonary valve at birth, as far as we know for the first time, in a neonate that had normal forward flow of blood as seen on Doppler sampling in fetal life.

Histological changes in the left and right ventricle in hearts with Ebstein's malformation and tricuspid valvar dysplasia: A morphometric study of patients dying in the fetal and perinatal periods

Both Ebstein's malformation and the related tricuspid valvar dysplasia are often associated with tricuspid regurgitation, and impaired right ventricular function may develop. Impaired function of the left ventricle in Ebstein's malformation has also been described. Interstitial fibrosis has been shown in the right and left ventricles of hearts with Ebstein's malformation from neonates, children, and adults. The objective of this study was to determine whether interstitial fibrosis seen in Ebstein's malformation is an intrinsic part of the congenital malformation or is acquired. From the fetal and perinatal periods, we compared 13 hearts with Ebstein's malformation (6 isolated and 7 with additional abnormalities) and 11 with tricuspid valvar dysplasia (3 isolated and 8 with additional abnormalities) with 16 controls. Three adult cases of isolated Ebstein's malformation in patients aged 17 to 20 years, were compared with 5 controls. The percentage of interstitial fibrous tissue and the thickness of the endocardium in the right and left ventricles were measured using histomorphometry. There were similar findings in Ebstein's malformation and tricuspid valvar dysplasia. Of 24 fetal and perinatal cases, 23 had normal interstitial fibrous tissue. Interstitial fibrosis was found in the right ventricle of only 1 perinatal heart with Ebstein's malformation and pulmonary stenosis. Of the 9 fetal cases, 4 had minimal right ventricular endocardial thickening (up to 10 μm). The left ventricular endocardium was normal in this group. Of the 6 perinatal cases with isolated Ebstein's malformation or tricuspid valvar dysplasia, 4 had right and 2 had left ventricular endocardial thickening (up to 345 μm). Of the 3 adult hearts with Ebstein's malformation, 2 had right ventricular endocardial thickening (47 and 225 μm) and 2 had right and 1 had left ventricular interstitial fibrosis. These results indicate that in both Ebstein's malformation and tricuspid valvar dysplasia the endocardial thickening develops in perinatal life, and in Ebstein's malformation the interstitial fibrosis develops in later life.

Spectrum of valvar abnormalities in Noonan's syndrome—a pathologic study

AbstractFour patients with the phenotypic characteristics of Noonan's syndrome presented in infancy with a suspected cardiac defect. The cardiac segmental connections were normal. All four were diagnosed to have valvar pulmonary stenosis by cross-sectional echocardiography, the valve being typically thickened and dysplastic as expected for the syndrome. In addition, all had hypertrophic cardiomyopathy and evidence for important abnormalities of the other cardiac valves. Two of the four patients died following cardiac surgery. Of the other two, one child died during interventional catheterization and another died while awaiting cardiac surgery. The cardiac abnormalities, confirmed at postmortem, were dysplastic pulmonary valve with stenosis (four patients), dysplastic aortic valve (three patients), supravalvar aortic stenosis (one patient), small and dysplastic tricuspid and mitral valves (four patients), hypertrophic obstructive cardiomyopathy affecting both ventricles, with asymmetric septal hypertrophy (four patients), atrial septal defect within the oval fossa (one patient). In addition to the usually described abnormalities of the pulmonary valve and ventricular myocardium, the patients described showed a wide spectrum of valvar dysplasia which has received little attention in the past. If these patients do indeed have Noonan's syndrome, and the evidence supports this contention, then these findings support the hypothesis of a more generalized disorder in the development of the ventricles and valves in the syndrome, which has a variable expression. They also stress the need to look carefully for abnormalities of valves other than the pulmonary valve in patients who present with symptoms in infanscy.

Correlation between echocardiographic and morphological investigations of lesions of the tricuspid valve diagnosed during fetal life.

To assess the degree of agreement between the fetal echocardiographic and postmortem examination of hearts from fetuses with severe malformations of the tricuspid valve. A retrospective study to analyse echocardiographic recordings and make comparisons with postmortem findings. Tertiary referral centre for fetal echocardiography. Institute for cardiac morphology. 19 cases shown to have severe malformation of the tricuspid valve by fetal echocardiography that died in the prenatal or neonatal period. Correlations between morphology and measurements made at echocardiography and necropsy. The echocardiographic diagnosis was Ebstein's malformation in seven and tricuspid valvar dysplasia in 12 fetuses. These findings were confirmed in six and eight cases at necropsy. In one false positive diagnosis of Ebstein's malformation, necropsy showed dysplasia of the leaflets of the tricuspid valve without displacement. In four cases with the echocardiographic diagnosis of valvar dysplasia, necropsy showed displacement, the hallmark of Ebstein's malformation. Associated malformations that are known to worsen prognosis were predicted correctly by echocardiography. Taking the mean duration of four weeks between echocardiographic and postmortem investigations, both methods showed cardiomegaly causing lung hypoplasia, right atrial dilatation, and relative hypoplasia of the pulmonary trunk, morphometric factors that may be responsible for the poor outcome. Mostly good agreement existed between the echocardiographic and postmortem measurements if cases with an interval of more than eight weeks between the measurements were excluded. Fetal echocardiography was proved to be a reliable technique in differentiating the variants of tricuspid valvar disease, in diagnosing associated cardiac lesions, and in predicting quantitative factors that can define the subsequent outcome.