Noonan syndrome and pregnancy outcomes

Background: Noonan syndrome is a genetic disorder with high prevalence of congenital heart defects, such as pulmonary stenosis, atrial septal defect and hypertrophic cardiomyopathy. Scarce data exists regarding the safety of pregnancy in patients with Noonan syndrome, particularly in the context of maternal cardiac disease. Study design: We performed a retrospective chart review of patients at Yale-New Haven Hospital from 2012 to 2020 with diagnoses of Noonan syndrome and pregnancy. We analysed medical records for pregnancy details and cardiac health, including echocardiograms to quantify maternal cardiac dysfunction through measurements of pulmonary valve peak gradient, structural heart defects and interventricular septal thickness. Results: We identified five women with Noonan syndrome (10 pregnancies). Three of five patients had pulmonary valve stenosis at the time of pregnancy, two of which had undergone cardiac procedures. 50% of pregnancies (5/10) resulted in pre-term birth. 80% (8/10) of all deliveries were converted to caesarean section after a trial of labour. One pregnancy resulted in intra-uterine fetal demise while nine pregnancies resulted in the birth of a living infant. 60% (6/10) of livebirths required care in the neonatal intensive care unit. One infant passed away at 5 weeks of age. Conclusions: The majority of mothers had pre-existing, though mild, heart disease. We found high rates of prematurity, conversion to caesarean section, and elevated level of care. No maternal complications resulted in long-term morbidity. Our study suggests that women with Noonan syndrome and low-risk cardiac lesions can become pregnant and deliver a healthy infant with counselling and risk evaluation.

Assessment of Biventricular Myocardial Function with 2-Dimensional Strain and Conventional Echocardiographic Parameters: A Comparative Analysis in Healthy Infants and Patients with Severe and Critical Pulmonary Stenosis

Our aim was to compare the global longitudinal and regional biventricular strain between infants with severe and critical pulmonary stenosis (PS), and controls; to compare pre- and post-procedural strain values in infants with severe and critical PS; and to assess the correlations between echocardiographic strain and conventional parameters. We conducted a retrospective single-center study. The comparisons of echocardiographic variables were performed using separate linear mixed models. The overall mean right ventricle (RV) regional strains measured before intervention in PS patients was significantly different when compared to the control group (p = 0.0324). We found a significant change in the left ventricle, RV, and inter-ventricular septum strain (IVS) values from basal to apical location (p < 0.05). IVS strain values showed a higher decrease in mean strain values from basal to apical in PS patients. There was no significant difference in means of baseline and post-interventional strain values in PS patients (p > 0.05). Following the strain analysis in patients with PS, we obtained statistically significant changes in the RV global-4-chamber longitudinal strain (RV4C). The RV4C, which quantifies the longitudinal strain to the entire RV, can be used in current clinical practice for the evaluation of RV function in infants with severe and critical PS. The longitudinal and segmental strain capture the pathological changes in the IVS, modifications that cannot be highlighted through a classical echocardiographic evaluation.

Serum N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker of Critical Pulmonary Stenosis in Neonates

Objectives: To determine the efficacy of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in predicting critical pulmonary stenosis (CPS) in neonates.Methods: All neonates with pulmonary stenosis (PS) admitted to the neonatal intensive care unit of Xinhua Hospital from October 2014 to December 2020 were retrospectively reviewed. Infants with serum NT-proBNP levels measured within 48 h after birth were enrolled and divided into CPS and non-CPS groups. Serum NT-proBNP levels and cardiac Doppler indices were compared between the two groups. Correlations were determined using the Spearman's rank correlation coefficient. Receiver operator characteristic curve analysis was used to explore the predictive value of NT-proBNP for identifying neonatal CPS.Results: Among 96 infants diagnosed with PS by echocardiography, 46 were enrolled (21 and 25 in the non-CPS and CPS groups, respectively). Serum NT-proBNP levels were significantly higher in the CPS group than in the non-CPS group [3,600 (2,040–8,251) vs. 1,280 (953–2,386) pg/ml, P = 0.003]. Spearman's analysis suggested a positive correlation between Ln(NT-proBNP) levels and the transvalvular pulmonary gradient (r = 0.311, P = 0.038), as well as between Ln(NT-proBNP) levels and pulmonary artery velocity (r = 0.308, P = 0.040). Receiver operating characteristic curve analysis showed that a cutoff serum NT-proBNP level of 2,395 pg/ml yielded a 66.7 and 78.9% sensitivity and specificity for identifying CPS, respectively. The area under the curve was 0.784 (95% CI, 0.637–0.931). A positive correlation was found between Ln(NT-proBNP) and length of hospital stay (r = 0.312, P &lt; 0.05).Conclusion: Serum NT-proBNP level was positively correlated with PS severity and could be used as a biomarker to identify CPS in neonates.

A case report of late physiologic repair of congenitally corrected transposition of the great arteries and pulmonary stenosis in a severely cyanotic patient: better late than never

Background Patients with congenitally corrected transposition of great arteries (ccTGA) not infrequently seek medical attention for the first time late in life. Optimal management of natural history ccTGA is debated and must be tailored. Case summary A 38 years old male patient was referred to our centre because of severe cyanosis and worsening dyspnoea. Investigations disclosed: situs solitus, mesocardia, double discordance, large ventricular septal defect (VSD), severe pulmonary stenosis, no significant atrioventricular valves regurgitation. The patient underwent physiologic repair: VSD closure, placement of a left ventricle to pulmonary artery conduit and epicardial atrio-biventricular pacemaker implantation. The conduit was intentionally undersized to promote tricuspid valve continence. Postoperative course was uneventful, trans-thoracic echocardiography showed good biventricular function without significant tricuspid regurgitation. At one month after discharge the patients is in NYHA class II. Discussion Management of late presenter patients with ccTGA depends on the associated lesion and estimation of surgical risk. In selected patients markedly symptomatic physiologic repair is a rationale option, providing a normal saturation and biventricular circulation with a significantly lower surgical risk as compared with anatomic repair.

Case series: Criss-cross Heart

Criss-cross heart (CCH) is a rare cardiac malformation which is characterized by crossing of the inflow streams of the two ventricles due to rotation of ventricular axis. The anomalies can be identified both atrioventricular concordance and discordance. The etiology of CCH is remaining unknown. Prominent symptom is cyanosis. The primary investigation is transthoracic echocardiography to identify this abnormality. Many patients need further investigation to review anatomy. Total correction is the aim for treatment but it is difficult for this complex anatomy. There were 5 patients who visited cardiology clinic at Queen Sirikit National Institute of Child Health (QSNICH) from 2002 to 2017. The objective is to review the treatment options that we performed in CCH. Most common associated anomalies were double outlet right ventricle and pulmonary stenosis. One patient died before surgical intervention; others were performed palliative surgery.

A Case of William’s Syndrome in a Ugandan Child: A Feasible Diagnosis Even in a Low-Resource Setting

Background: Williams–Beuren syndrome (WS) is a rare, complex, congenital developmental disorder including cardiovascular manifestations, intellectual disability and a peculiar cognitive and behavior profile. Supravalvular aortic stenosis (SVAS) is the most frequent cardiovascular abnormality in WS children. Data on WS patients in sub-Saharan Africa are scarce. A genetic study is usually required for a definite diagnosis, but genetic testing is often unavailable in developing countries and the combination of a typical clinical phenotype and echocardiographic profile helps to confirm the diagnosis. Case Report: We report the case of a 5-year-old Ugandan child admitted to a large no profit hospital after he was initially managed as a case of infective endocarditis. A physical examination revealed the typical features of WS. A cardiac echo showed severe SVAS (peak gradient 80 mmHg) with a normal anatomy and function of the aortic valve and mild valvular pulmonary stenosis. The child also had a moderate intellectual disability and a characteristic facies consistent with WS. Conclusion: We present the first reported case of WS in Uganda. Cardiac echo and a characteristic clinical picture could be enough to exclude more common causes of heart failure (i.e., rheumatic heart disease) and to make the diagnosis even when specific genetic tests are not available.

‘Superimposed miracles’ An extremely rare case of a septuagenarian with an unrepaired tetralogy of Fallot: a case report

Background Although the life expectancy of patients with tetralogy of Fallot (TOF) is comparable to that of the general population due to advancements in surgical intervention, if untreated, patients with TOF may die during their childhood. However, it has been anecdotally reported that a small number of patients with unrepaired TOF survived into their senescence. Case Summary A 71-year-old man with a history of multiple heart failure admissions was referred to our institute after successful cardiopulmonary arrest resuscitation. Transthoracic echocardiography showed the overriding of the aorta on a large ventricular septal defect and right ventricular hypertrophy, along with severe pulmonary stenosis (PS), all of which indicated unrepaired TOF. Computed tomography revealed a patent Blalock-Taussig shunt, which was constructed at the age of 19 years. Coronary angiography revealed multivessel coronary stenoses. Although radical intracardiac repair was not performed due to his multiple comorbidities, his heart failure symptoms were significantly improved owing to proper medication titration. One year following discharge, the patient was well and enjoyed playing golf. Discussion Specific anatomical, functional and haemodynamic characteristics may be required for the long-term survival of patients with TOF. PS should be initially mild to guarantee pulmonary flow during childhood and adolescence, and gradual PS exacerbation should be paralleled with systemic-to-pulmonary collateral development or an extra-cardiac shunt. Moreover, reduced left ventricular compliance may act as a balancing factor against a right-to-left shunt. The presence of all of these special requirements may have contributed to the unusual survival for this patient.

English Case report: Succesfully Management of Critical Pulmonary Stenosis in a 12-Month-Old Boy By percutaneous transluminal balloon valvuloplasty

Critical pulmonary stenosis (PS) is used in infants born with very severe narrowing valves and requires treatment soon after birth. At four months old, an A-12-month-old boy was diagnosed with critical pulmonary stenosis but still successfully managed by percutaneous transluminal balloon valvuloplasty (PTBV) with satisfactory results without serious complications. Since he was born, cyanosis was seen at his lips and fingertip, with oxygen saturation around 60% until 70%. Echocardiography showed critical pulmonary stenosis, atrial septal defect (ASD), and patent ductus arteriosus (PDA). Percutaneous transluminal balloon valvuloplasty (PTBV) is accepted as the treatment of choice for critical pulmonary valve stenosis in many centers worldwide with significant results. After PTBV, he experienced improvement condition as no cyanosis was observed and oxygen saturation was 96%. This case was our first PTBV intervention case in our hospital and gave satisfactory results, although the intervention was delayed due to our limited resources before. Keywords: cyanosis, critical pulmonary stenosis, percutaneous transluminal balloon valvuloplasty