Comparative effectiveness among thromboprophylaxis strategies after the Fontan operation: A systematic review and network meta-analysis.

INTRODUCTION: A variety of thromboprophylaxis regimens have been administered in patients following the Fontan procedure. However, consensus guidelines regarding the optimal thromboprophylaxis strategy have not yet been developed. METHOD: A network meta-analysis was conducted to evaluate the comparative effectiveness among available thromboprophylaxis regimens and major bleeding events associated with these regimens. RESULTS: A total of 28 comparative studies with 4430 Fontan patients were included. The incidence of thromboembolic events (TE) was significantly lower in individuals who underwent thromboprophylaxis compared to those who did not. Compared to a no-treatment strategy, nonvitamin K oral anticoagulants (NOACs) showed the largest treatment effect for preventing TE (OR = 0.08, 95 % CI 0.03 to 0.21), followed by warfarin (OR = 0.16, 95 % CI 0.10 to 0.27), and aspirin (OR = 0.23, 95 % CI 0.14 to 0.38). Indeed, NOACs were significantly more effective than aspirin in preventing TE (OR = 0.35, 95 % CI 0.14 to 0.84). Aspirin was associated with the lowest occurrence of major bleeding events, followed by NOACs, no medication, and warfarin. NOACs were shown to possess a highly favorable overall profile. CONCLUSION: Prescribing thromboprophylaxis drugs, either antiplatelets or anticoagulants, may be more effective in preventing TE after the Fontan operation than not doing so. Among the included regimens, NOACs demonstrated significantly greater efficacy than aspirin; however, they did not show statistically significant superiority over warfarin. Aspirin exhibited lower rates of major bleeding compared to both NOACs and warfarin. Overall, NOACs tended to offer the most advantageous balance of efficacy and safety. However, the findings should be interpreted considering the certainty and limitations of the evidence, including potential residual confounding in observational studies.

Cardiac dysfunctions in children with drug-resistant epilepsy.

Objective: There were reports of cardiac dysfunction that led to sudden unexpected death in epilepsy (SUDEP) in patients with epilepsy. Early detection of cardiac dysfunction can lead to early management to prevent sudden cardiac death in these patients. The objective of our study is to assess cardiac functions in children with drug-resistant epilepsy (DRE) compared with the normal population by using a standard echocardiogram (SE), tissue Doppler imaging (TDI) and myocardial strain evaluations (MSE). Method: Twenty-seven children who have been diagnosed with DRE based on the International League against Epilepsy (ILAE) were included in the study, along with 27 children whose ages match those of the normal control group. Results: Seventeen children, median age 12 years old, were using more than four anti-seizure medications. Structural brain lesions were the most common cause of epilepsy, 55.6% (15). Generalized tonic-clonic seizures were the most common seizure type, 55.6% (15). Children with DRE had a lower early mitral valve E wave inflow velocity compared with the control group (p < 0.05). They also had lowered early diastolic velocities (e') and myocardial performance index (MPI) when compared with the control group (p < 0.05). There was a statistically significant difference in left ventricular myocardial strain in children with DRE, with an average of -21.1 (IQR -23.5 and -19.4) and control, -25.5 (IQR -27.3 and -24.2). Significance: Children with DRE have an impairment of left ventricular diastolic function and myocardial strain, which could indicate decreased myocardial deformation and contraction compared with controls. These cardiological assessments can be used to evaluate children with DRE for early diagnosis and management of their cardiac dysfunction.

Comparison of Right Ventricular Outflow Tract Reconstruction Techniques on Mid-Term Pulmonic Valve Fate.

Introduction: The pulmonic valve-sparing technique (PVS) is an emerging approach of right ventricular outflow tract reconstruction in tetralogy of Fallot (TOF) correction aimed at reducing the incidence of pulmonic regurgitation (PR) and the need for subsequent reintervention. This study aims to compare the long-term occurrence of moderate to severe PR/stenosis (PR/PS) between three different approaches. Patients and Methods: We conducted a retrospective cohort study involving 173 patients who underwent TOF correction at Chiang Mai University hospital between January 2006 and December 2016. The patients were divided into three groups: transannular patch (TAP; n = 88, 50.9%), monocusp insertion (MCI; n = 40, 23.1%), and PVS (n = 45, 26%). The study assessed freedom from moderate to severe PR/PS. Results: The median overall follow-up time was 79.8 months (interquartile range: 50.7-115.5 months. The PVS exhibited larger PV Z-score (-2.6 ± 2.3 mm, P < .001), with predominantly tricuspid morphology (64.4%). The PVS had significantly shorter median ventilator time, intensive care unit stay, hospital stay, and longer median follow-up time. Postoperative moderate-severe PR was lower in the PVS group (P < .001), with no significant difference in PS (P = .356) and complications among the groups. Freedom from moderate-severe PR/PS was longer in the MCI group (2.8, 0.2-42.3 months vs 30.9, 0.2-50.9 months, respectively). Multivariable analysis showed TAP and MCI had a higher risk of developing moderate-severe PR (hazard ratio [HR] 2.51; 95% confidence interval [CI] 1.23-5.13 vs HR 1.41; 95%CI 0.59-3.38) but lower risk of moderate-severe PS (HR 0.14; 95%CI 0.02-0.9 vs HR 0.39; 95%CI 0.05-3.19). Conclusion: Pulmonic valve-sparing reconstruction showed promise in preventing late moderate-severe PR in patients with favorable PV anatomy. However, it should be noted that this technique is associated with a higher incidence of PS.

Correlation between pressure gradient from echocardiography and peak-to-peak pressure gradient from cardiac catheterization or surgery in patients with coarctation of aorta.

The gold standard for assessing pressure gradients (PG) across coarctation involves measurements obtained through cardiac catheterization or surgical intervention. There has been ongoing discussion regarding the accuracy of non-invasive methods for estimating these gradients. This study sought to establish the correlation and agreement between the systolic blood pressure (SBP) gradient between the upper and lower extremities, as well as, the mean and maximum PG derived from echocardiography, in comparison to the peak-to-peak pressure gradient obtained from either cardiac catheterization or surgery. We conducted a retrospective study on patients < 18 years diagnosed with coarctation at Chiang Mai University Hospital from 2011 to 2022. The study involved the measurement of the SBP gradient between the upper and lower extremities, mean and maximum PG using echocardiography, peak-to-peak pressure gradient obtained from cardiac catheterization, and pressure gradient recorded during surgical procedures. The Spearman's correlation and Bland-Altman analysis were employed to assess correlation and agreement. Fifty-four patients with aortic coarctation were enrolled. The mean PG measured by echocardiography showed a significantly moderate correlation (r = 0.78, p < 0.001) and the highest level of agreement according to Bland Altman plots, in comparison to the peak-to-peak pressure gradient measured during both cardiac catheterization and surgical procedure. The max PG demonstrated a notable overestimation compared to the gold standard (mean difference + 13.14 with a slope of biases + 0.64, p < 0.001). The mean PG obtained through echocardiography has more potential to be applied in practical application in predicting pressure gradient in patients with coarctation.

Development of a clinical prediction tool for extubation failure in pediatric cardiac intensive care unit.

Introduction/objective: Extubation failure in pediatric patients with congenital or acquired heart diseases increases morbidity and mortality. This study aimed to develop a clinical risk score for predicting extubation failure to guide proper clinical decision-making and management. Methods: We conducted a retrospective study. This clinical prediction score was developed using data from the Pediatric Cardiac Intensive Care Unit (PCICU) of the Faculty of Medicine, Chiang Mai University, Thailand, from July 2016 to May 2022. Extubation failure was defined as the requirement for re-intubation within 48 h after extubation. Multivariable logistic regression was used for modeling. The score was evaluated in terms of discrimination and calibration. Results: A total of 352 extubation events from 270 patients were documented. Among these, 40 events (11.36%) were extubation failure. Factors associated with extubation failure included history of pneumonia (OR: 4.14, 95% CI: 1.83-9.37, p = 0.001), history of re-intubation (OR: 5.99, 95% CI: 2.12-16.98, p = 0.001), and high saturation in physiologic cyanosis (OR: 5.94, 95% CI: 1.87-18.84, p = 0.003). These three factors were utilized to develop the risk score. The score showed acceptable discrimination with an area under the curve (AUC) of 0.77 (95% CI: 0.69-0.86), and good calibration. Conclusion: The derived Pediatric CMU Extubation Failure Prediction Score (Ped-CMU ExFPS) could satisfactorily predict extubation failure in pediatric cardiac patients. Employing this score could promote proper personalized care. We suggest conducting further external validation studies before considering implementation in practice.

Outcome following acute and recurrent rheumatic fever.

BACKGROUND: Rheumatic carditis is the leading cause of permanent disability caused by damage of the cardiac valve. This study aimed to determine the outcome and predictors of valve surgery in patients with acute rheumatic fever (ARF) and recurrent rheumatic fever (RRF). METHODS: This was a retrospective study of patients diagnosed with ARF and RRF between 2006 and 2021. The predictors of valve surgery were analysed using multivariable Cox proportional regression. RESULTS: The median age of patients with ARF and RRF (n=92) was 11 years (range 5-18). Seventeen patients (18%) were diagnosed with RRF. The most common presenting symptoms included clinical carditis (87%), heart failure (HF) (63%), fever (49%) and polyarthralgia (24%). Patients with moderate-to-severe rheumatic carditis (88%) were given prednisolone. After treatment, the severity of valvular regurgitation was reduced in 52 patients (59%). Twenty-three patients (25%) underwent valve surgery. The incidence of HF, RRF, severe mitral regurgitation on presentation, left ventricular enlargement and pulmonary hypertension was greater in the surgical group than in the non-surgical group. Recurrent rheumatic fever (hazard ratio 7.9, 95% CI 1.9-33.1), tricuspid regurgitation (TR) gradient ≥ 42 mmHg (HR 6.3, 95%CI 1.1-38.7) and left ventricular end-diastolic dimension (LVEDD) ≥6 cm (HR 8.7, 95% CI 2.1-35.9) were predictors of valve surgery (multivariable Cox proportional regression analysis). CONCLUSION: Clinical carditis was the most common presenting symptom in patients with ARF and RRF. The majority of patients responded positively to prednisolone. These findings highlight the predictors of valve surgery following ARF, including RRF, TR gradient ≥ 42 mmHg and LVEDD ≥ 6 cm.Abbreviations: ARF: acute rheumatic fever; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; GAS: group A beta-haemolytic Streptococcus; HF: heart failure; HR: hazard ratio; LVEDD: left ventricular end-diastolic dimension; MR: mitral regurgitation; RHD: rheumatic heart disease; RRF: recurrent rheumatic fever; TR: tricuspid regurgitation.

Mitochondrial dysfunction is associated with the severity of liver fibrosis in patients after the Fontan operation.

The gold standard for determining the severity of liver disease in Fontan patients is now liver biopsy. Since it is an invasive procedure, this study determined the possibility of applying mitochondrial function from isolated peripheral blood mononuclear cells (PBMCs) as a non-invasive indicator of liver fibrosis. Fontan patients (n = 37) without known liver disease were analysed cross-sectionally. Patients were classified according to their histology using the METAVIR score as follows; F0/F1-no/mild fibrosis; F2-moderate fibrosis; and F3/F4-cirrhosis. Peripheral blood mononuclear cells were assessed for mitochondrial activity and apoptosis. This study did not find any significant differences in cardiac function among the groups according to liver histology. Interestingly, our findings indicated a significant decrease in maximal respiration and spare respiratory capacity, in both the moderate (F2) and cirrhosis (F3/F4) groups compared with the group without significant fibrosis (F0/F1). Moreover, the cirrhosis group exhibited higher levels of apoptosis and lower levels of live cells, compared with both the moderate and no significant fibrosis groups. In conclusion, the degree of liver fibrosis in Fontan patients is strongly correlated with mitochondrial dysfunction in PBMCs. Mitochondrial function and apoptosis could potentially serve as novel markers for tracking the progression of liver fibrosis in these patients.

Pheochromocytoma presenting with QT prolongation and catecholamine-induced myocarditis in a child.

Pheochromocytomas are catecholamine-producing tumors derived from the adrenomedullary chromaffin cells. The presentation is a classic triad of episodic headaches, sweating, and tachycardia. Hypertensive crisis can occur due to profuse catecholamine excess. Unusual manifestations mimicking cardiogenic shock, arrhythmia, and myocarditis have been rarely reported in children. We present a case with uncommon manifestations of pheochromocytoma in a child, including the episodes of exercised-induced presyncope with QT prolongation, and subsequently cardiogenic shock due to fulminant myocarditis. He later developed hypertensive crisis. The adrenal mass on abdominal computed tomography with an increased chromogranin A level and elevated plasma normetanephrine, and the histological study confirmed the diagnosis of pheochromocytoma. Cardiac functions completely recovered after adrenalectomy. Genetic testing was positive for von Hippel-Lindau syndrome. We describe pheochromocytoma crisis presenting with prolonged QT and catecholamine-induced myocarditis. We discuss the clues to assist in the diagnosis of this condition and its appropriate treatment.

Comparison of fetal and neonatal cardiac morphology between the infants of mothers with well-controlled gestational diabetes mellitus and normal controls.

OBJECTIVE: To compare fetal and neonatal cardiac morphology in fetuses of mothers with gestational diabetes mellitus (GDM) with the controls. PATIENTS AND METHODS: Pregnant women at average risk of GDM underwent 100-g, 3-h-OGTT at 24-28 weeks of gestation for diagnosis of GDM. Both GDM group and the control group underwent fetal echocardiography at 32-36 weeks to assess cardiac dimensions. The neonates underwent echocardiography within 48 h after birth to assess cardiac morphology. RESULTS: A total of 154 pregnant women were recruited, including 60 in the GDM group and 94 in the control group. All of the study group were well controlled for GDM. Most baseline characteristics of both groups were comparable. All obstetric outcomes were not significantly different between the two groups. Morphological cardiac dimensions in the fetuses and newborns of both groups were also not significant different. Subgroup analysis in the study group showed no significantly different in cardiac morphology between the group with diet control and that of insulin control. CONCLUSION: Fetal and neonatal cardiac morphologic changes among mothers with well-controlled GDM are not significantly different from those in the controls. It is possible that good control of maternal blood glucose can prevent fetal and neonatal cardiac abnormalities.

Hydrogen therapy as a potential therapeutic intervention in heart disease: from the past evidence to future application.

Cardiovascular disease is the leading cause of mortality worldwide. Excessive oxidative stress and inflammation play an important role in the development and progression of cardiovascular disease. Molecular hydrogen, a small colorless and odorless molecule, is considered harmless in daily life when its concentration is below 4% at room temperature. Owing to the small size of the hydrogen molecule, it can easily penetrate the cell membrane and can be metabolized without residue. Molecular hydrogen can be administered through inhalation, the drinking of hydrogen-rich water, injection with hydrogen-rich-saline, and bathing of an organ in a preservative solution. The utilization of molecular hydrogen has shown many benefits and can be effective for a wide range of purposes, from prevention to the treatment of diseases. It has been demonstrated that molecular hydrogen exerts antioxidant, anti-inflammatory, and antiapoptotic effects, leading to cardioprotective benefits. Nevertheless, the exact intracellular mechanisms of its action are still unclear. In this review, evidence of the potential benefits of hydrogen molecules obtained from in vitro, in vivo, and clinical investigations are comprehensively summarized and discussed with a focus on the cardiovascular aspects. The potential mechanisms involved in the protective effects of molecular hydrogen are also presented. These findings suggest that molecular hydrogen could be used as a novel treatment in various cardiovascular pathologies, including ischemic-reperfusion injury, cardiac injury from radiation, atherosclerosis, chemotherapy-induced cardiotoxicity, and cardiac hypertrophy.

Predictive factors of extubation failure in pediatric cardiac intensive care unit: A single-center retrospective study from Thailand.

Introduction/objective: Extubation failure increases morbidity and mortality in pediatric cardiac patients, a unique population including those with congenital heart disease or acquired heart disease. This study aimed to evaluate the predictive factors of extubation failure in pediatric cardiac patients and to determine the association between extubation failure and clinical outcomes. Methods: We conducted a retrospective study in the pediatric cardiac intensive care unit (PCICU) of the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, from July 2016 to June 2021. Extubation failure was defined as the re-insertion of the endotracheal tube within 48 hours after extubation. Multivariable log-binomial regression with generalized estimating equations (GEE) was performed to explore the predictive factors associated with extubation failure. Results: We collected 318 extubation events from 246 patients. Of these, 35 (11%) events were extubation failures. In physiologic cyanosis, the extubation failure group had significantly higher SpO2 than the extubation success group (P < 0.001). The predictive factors associated with extubation failure included a history of pneumonia before extubation (RR 3.09, 95% CI 1.54-6.23, P = 0.002), stridor after extubation (RR 2.57, 95% CI 1.44-4.56, P = 0.001), history of re-intubation (RR 2.24, 95% CI 1.21-4.12, P = 0.009), and palliative surgery (RR 1.87, 95% CI 1.02-3.43, P = 0.043). Conclusion: Extubation failure was identified in 11% of extubation attempts in pediatric cardiac patients. The extubation failure was associated with a longer duration of PCICU stay but not with mortality. Patients with a history of pneumonia before extubation, history of re-intubation, post-operative palliative surgery, and post-extubation stridor should receive careful consideration before extubation and close monitoring afterward. Additionally, patients with physiologic cyanosis may require balanced circulation via regulated SpO2.

Prevalence and predictive factors of malnutrition in Thai children with congenital heart disease and short-term postoperative growth outcomes.

Background: Growth restriction is still a common problem in children with congenital heart disease (CHD). Evidence demonstrates that performing cardiac surgery in appropriate timing may result in better growth outcome. Aim: To investigate prevalence and associated factors of malnutrition in pediatric patients with CHD who underwent cardiac surgery. In addition, post-operative growth outcomes at two weeks following cardiac surgery were also assessed. Methods: A retrospective cohort study was conducted in pediatric patients who underwent cardiac surgery at Chiang Mai University Hospital between January and September 2014. Results: One hundred patients with a median age of 28.5 months (range 14-62 months) were enrolled. Two-third of these patients had at least one form of malnutrition before receiving surgical treatment while wasting, stunting and combined wasting-stunting accounted for 23%, 28%, and 15% of patients, respectively. Multiple logistic regression analysis demonstrated that congestive heart failure-related symptoms were significantly associated with increasing risk of malnutrition (adjusted OR 4.4; 95% CI 1.78-11.26, p = 0.001). Two weeks after hospital discharge, wasting patients with regardless of stunting had significantly improved weight for height (WHZ) and weight for length Z-scores (WLZ) compared to growth parameters at the time of cardiac surgery, p = 0.012 and p < 0.001, respectively. Conclusion: The prevalence of acute and chronic malnutrition in pediatric patients with CHD who underwent cardiac surgery was very high in this study. Children with congestive heart failure had a four-time at risk of undernutrition. In short-term, cardiac surgery may mitigate acute malnutrition of these patients.

Pre-implantation genetic testing for Marfan syndrome using mini-sequencing.

Marfan syndrome (MFS1) is an autosomal dominant condition causing aortopathy including fatal aortic dissection. This study aimed to perform clinical PGT-M in a family with a history of MFS1 for two generations. A family with two members affected by MFS1 approached the hospital for PGT-M. The couple decided to join the project following extensive counselling and informed consent was obtained. The mutation contributory to MFS1 was identified using whole-exome sequencing (WES). A novel PGT-M protocol using multiplex fluorescent PCR and mini-sequencing was developed and tested. Ten blastocysts were subjected to PGT-M in two clinical PGT cycles. Mini-sequencing revealed four normal and six affected embryos. Microsatellite-based linkage analysis confirmed mutation analysis results in all samples. The embryos diagnosed as normal (non-MFS1) were chosen for transfer. A pregnancy was obtained in the third embryo transfer. Invasive prenatal diagnosis confirmed the normal genotype of the baby. This study demonstrated comprehensive management using the application of clinical-based diagnosis, WES for mutation identification within the MFS1 gene, mini-sequencing for embryo selection and microsatellite-based linkage analysis for backup of PGT-M results and contamination detection to assist couples in having a healthy child when there was a family history of Marfan syndrome.Impact StatementWhat is already known on this subject? Marfan syndrome (MFS1, OMIM#154700) is an autosomal dominant condition causing aortopathy including fatal aortic dissection. Pre-implantation genetic testing (PGT) is an alternative to traditional invasive prenatal diagnosis (PND) giving the couples the chance of starting pregnancy with the confidence that the baby will be unaffected. Most of the previous PGT reports employed microsatellite-based linkage analysis. A few PGT studies used sequencing, mini-sequencing and mutation analysis; however, the details of the techniques were not described.What do the results of this study add? Single-cell PCR protocol using multiplex fluorescent PCR and mini-sequencing was developed and validated. Two clinical PGTs cycles for Marfan syndrome were performed. A healthy baby was resulted. The details of multiplex fluorescent PCR and mini-sequencing protocols are described in this study so that the procedures can be reproduced.What are the implications of these findings for clinical practice and/or further research? Embryo selection can help the family suffering from Marfan syndrome for two generations to start a pregnancy with confidence that their child will be unaffected. This study also shows the use of a mini-sequencing protocol for PGT, which can be a universal protocol for other mutations by changing the PCR primers and mini-sequencing primers.

Screening modalities for the diagnosis of Fontan-associated liver disease: evidence from the past for future development.

Approximately 70,000 patients who have undergone the Fontan operation worldwide survive into adulthood, however the majority of these patients are faced with long-term post-operative complications due to specific hemodynamic changes. Fontan-associated liver disease (FALD) is a challenging complication characterized by various spectra. Of these, liver congestion and liver fibrosis potentially lead to cirrhosis and liver nodules. The most serious condition associated with the development of liver nodules is hepatocellular carcinoma. Various non-invasive modalities including blood tests, ultrasound scans of the upper abdomen, ultrasound elastography of the liver, computed tomography scans, magnetic resonance imaging and magnetic resonance elastography of the liver have been used as alternatives to liver biopsies for FALD assessment in post-Fontan patients. To date, a detailed understanding of the pathophysiology and natural history of these patients, and the most appropriate modality for the effective investigation of this condition is incomplete. In this comprehensive review, reports regarding the currently available screening modalities used in the detection of FALD are summarized and discussed. The findings of this review, including identification of any current knowledge gaps, can pave the way for the development of effective future strategies in the surveillance and ultimately the treatment of post-Fontan patients.

Liver nodules after the Fontan operation: role of the computerised tomography scan.

Currently, there is an increasing prevalence of liver nodules in patients following the Fontan operation. The appropriate non-invasive modalities have been applied to assess a diagnosis of Fontan-associated liver disease. The aims of this study were to determine the prevalence and associated factors for the presence of liver nodules using CT scan. A cross-sectional study of 34 patients older than 15 years of age was recruited. Ultrasound upper abdomen, ultrasound liver elastography, and CT scan of the upper abdomen were performed after the Fontan operation. The median age of patients was 20 years (range 14-36 years). The median age at the Fontan operation was 7 years (range 5-17 years) and the duration after the Fontan operation was 12 years (range 4-22 years). The prevalence of liver nodules was 62% as detected by CT scans. Hepatic vein pressure in patients with liver nodules was significantly higher than in those without liver nodules. Hepatic vein pressure above 13 mmHg was a factor associated with liver nodules. There was little agreement between the ultrasound of the upper abdomen and CT scan of the upper abdomen in the evaluation of liver nodules. Hepatic pressure was the only associated factor for the occurrence of liver nodules in patients following the Fontan operation. The prevalence of liver nodules was very high after the Fontan operation. The upper abdomen CT scan should be performed for the surveillance of liver nodules in every Fontan patient over the age of 15 years.

Dental Anomalies in Ciliopathies: Lessons from Patients with BBS2, BBS7, and EVC2 Mutations.

Objective: To investigate dental anomalies and the molecular etiology of a patient with Ellis−van Creveld syndrome and two patients with Bardet−Biedl syndrome, two examples of ciliopathies. Patients and Methods: Clinical examination, radiographic evaluation, whole exome sequencing, and Sanger direct sequencing were performed. Results: Patient 1 had Ellis−van Creveld syndrome with delayed dental development or tooth agenesis, and multiple frenula, the feature found only in patients with mutations in ciliary genes. A novel homozygous mutation in EVC2 (c.703G>C; p.Ala235Pro) was identified. Patient 2 had Bardet−Biedl syndrome with a homozygous frameshift mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7. Patient 3 had Bardet−Biedl syndrome and carried a heterozygous mutation (c.389_390delAC; p.Asn130ThrfsTer4) in BBS7 and a homozygous mutation in BBS2 (c.209G>A; p.Ser70Asn). Her clinical findings included global developmental delay, disproportionate short stature, myopia, retinitis pigmentosa, obesity, pyometra with vaginal atresia, bilateral hydronephrosis with ureteropelvic junction obstruction, bilateral genu valgus, post-axial polydactyly feet, and small and thin fingernails and toenails, tooth agenesis, microdontia, taurodontism, and impaired dentin formation. Conclusions: EVC2, BBS2, and BBS7 mutations found in our patients were implicated in malformation syndromes with dental anomalies including tooth agenesis, microdontia, taurodontism, and impaired dentin formation.

Prenatal Sonographic Features of CHARGE Syndrome.

CHARGE syndrome is a rare autosomal dominant disorder, associated with coloboma (C), heart defects (H), choanal atresia (A), retardation of growth and/or central nervous system (R), genitourinary anomalies (G) and ear abnormalities (E). Prenatal diagnosis of the syndrome is very rare but may be suspected when a combination of such abnormalities is identified. We describe a prenatally suspected case of CHARGE syndrome due to unique findings of cardiac defects (DORV) in combination with minor clues, including a structurally malformed ear with persistent non-response to an acoustic stimulation (which has never been prenatally described elsewhere), renal malrotation and growth restriction. Postnatal diagnosis was made based on confirmation of the prenatal findings and additional specific findings of bilateral coloboma, choanal atresia and ear canal stenosis. Finally, molecular genetic testing by whole exome sequencing of the neonate and her parents revealed a novel de novo heterozygous frameshift c.3506_3509dup variant in the CHD7 gene, confirming the clinical diagnosis of CHARGE syndrome. In conclusion, we describe unique prenatal features of CHARGE syndrome. Educationally, this is one of the rare examples of CHARGE syndrome, comprising all of the six specific anomalies as originally described; it is also supported by the identification of a specific genetic mutation. The identified genetic variant has never been previously reported, thereby expanding the mutational spectrum of CHD7. Finally, this case can inspire prenatal sonographers to increase awareness of subtle or minor abnormalities as genetic sonomarkers.

Risk factors for morbidity and mortality after a bidirectional Glenn shunt in Northern Thailand.

OBJECTIVES: Owing to the evolution of surgical techniques, the survival rate of patients undergoing a bidirectional Glenn shunt has improved. However, the morbidity and mortality are still high. The aims of this study were to determine the survival rate and risk factors influencing the morbidity and mortality in patients with a functional univentricular heart after a bidirectional Glenn shunt. METHODS: One hundred and fifty-one patients who had undergone a bidirectional Glenn operation were enrolled. Early worse outcomes were defined as postoperative death within 30 days and a hospital stay ≥ 30 days. RESULTS: The median age was 7.1 years (range 0.3-26 years). The median age at the time of the Glenn operation was 2.2 years (range 0.2-15.9 years). The survival rates of patients at 1-, 5-, 10- and 15-year after the Glenn operation were 89%, 79%, 75%, and 72%, respectively. The predictors for the mortality were preoperative mean pulmonary artery pressure ≥ 17 mmHg, preoperative pulmonary vascular resistance index ≥ 3.1 Wood Units·m2 and atrioventricular valve regurgitation. In addition, the independent predictors of an early worse outcome included preoperative mean pulmonary artery pressure ≥ 17 mmHg and diaphragmatic paralysis. CONCLUSION: The presence of preoperative atrioventricular valve regurgitation, preoperative mean pulmonary artery pressure ≥ 17 mmHg, preoperative pulmonary vascular resistance index ≥ 3.1 Wood Units·m2, or diaphragmatic paralysis were found to be independent risk factors requiring the good patients' selection for the Glenn operation and early aggressive management of the diaphragmatic paralysis for reducing morbidity to ensure successful candidature for Fontan completion.

Survival and predictors of mortality in patients after the Fontan operation.

BACKGROUND: As a result of the surgical techniques now being employed, the survival rate in patients after undergoing the Fontan operation has improved. The aims of this study were focused on determining the survival rate and predictors of early mortality. METHODS: In a retrospective cohort study, 117 consecutive patients who underwent the Fontan operation were recruited. Multivariate Cox proportional regression analysis was used to assess the predictors of early mortality, defined as death within 30 days after the Fontan operation. RESULTS: The median follow-up time was 6.1 years. The median age at the time of the Fontan operation was 5.7 years. Survival rates in the patients at 5, 10, and 15 years postoperatively were 92%, 87% and 84%, respectively. Using univariate Cox regression analysis, the predictors of early mortality were found to be postoperative mean pulmonary artery pressure ≥23 mm Hg (hazard ratio 26.0), renal failure (hazard ratio 9.5), heterotaxy syndrome (hazard ratio 5.3), and uncorrected moderate or severe atrioventricular valve regurgitation (hazard ratio 9.4). After adjusting for confounding factors using multivariate Cox regression analysis, the predictors of early mortality were found to be postoperative mean pulmonary artery pressure ≥23 mm Hg (hazard ratio 23.2) and uncorrected moderate or severe atrioventricular valve regurgitation (hazard ratio 8.2). CONCLUSIONS: Uncorrected moderate or severe atrioventricular valve regurgitation and postoperative mean pulmonary artery pressure ≥23 mm Hg are independent predictors of early mortality after the Fontan operation. Patients with these factors should undergo aggressive management to minimize morbidity and mortality.

Associated Factors of Liver Disease After Fontan Operation in Relation to Ultrasound Liver Elastography.

Although the Fontan operation can improve outcomes, surviving patients still face Fontan-associated liver disease (FALD). The aim of this study was to determine the associated factors of FALD in relation to ultrasound liver elastography. A cross-sectional study was conducted for all patients on whom an ultrasound upper-abdomen and ultrasound liver elastography was performed at more than 1 year after the Fontan operation. The data consisted of the age at operation, type of Fontan operation, and laboratory data such as gamma-glutamyl transferase (GGT), aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) score. Cardiovascular evaluations included echocardiography and cardiac catheterization. Eighty patients with a median age of 12 years (range 5-36 years) were eligible for the study. The prevalence of FALD was 41%. For the purpose of univariate logistic regression analysis, the age at the Fontan operation, time elapsed since the Fontan operation, previous Glenn shunt, presence of fenestration, mean pulmonary artery pressure and IVC pressure post-Fontan operation, platelet count, GGT, and FIB-4 score were considered to be factors significantly associated with FALD. Following an adjustment by multivariate logistic regression analysis, age greater than 7 years at the time of Fontan procedure, time elapsed of more than 9 years since the procedure, and GGT level > 130 U/L were found to be significantly associated with FALD. Patients with these factors should be investigated for FALD.