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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 Statement

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. 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. 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. 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.

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.

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.

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.

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.

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

Maternal autoantibodies to Ro/SSA are often linked to congenital heart block and rarely associated with structural defects. We describe the case of a fetus with anti-Ro-mediated second-degree block at 19 weeks, which progressed to a complete block, fibroelastosis, atrioventricular valve insufficiency, and semilunar valve stenosis/insufficiency at 20, 22, 24, and 26 weeks, respectively, although the fetus received transplacental anti-arrhythmic drugs. The 2150-g fetus was vaginally delivered at 35 weeks. An external pacemaker was inserted immediately after birth and replaced with permanent pacemaker at the age of 3 months. The newborn has had a good outcome with well-controlled heart rate.

Aortopulmonary window (APW) is a rare congenital heart defect, characterized by a connection between the ascending aorta and the pulmonary trunk before bifurcation. Prenatal diagnosis of APW is essential, as a surgical correction early after birth is required in most cases to prevent congestive heart failure secondary to high pulmonary blood flow. We report a series of three cases of APW that were detected by prenatal echocardiography. The key feature of diagnosis is demonstration of connection between the pulmonary artery and the aorta above the level of the two semilunar valves. Based on our cases and literature review, diagnostic clues for prenatal diagnosis of APW are summarized and proposed.

Mutations inTFAP2B has been reported in patients with isolated patent ductus arteriosus (PDA) and Char syndrome. We performed mutation analysis of TFAP2B in 43 patients with isolated PDA, 7 patients with PDA with other congenital heart defects and 286 patients with isolated tooth agenesis with or without other dental anomalies. The heterozygous c.1006G>A mutation was identified in 20 individuals. Those mutation carriers consisted of 1 patient with term PDA (1/43), 16 patients with isolated tooth agenesis with or without other dental anomalies (16/286; 5.6%), 1 patient with PDA and severe valvular aortic stenosis and tooth agenesis (1/4) and 2 normal controls (2/100; 1%). The mutation is predicted to cause an amino-acid substitution p.Val336Ile in the TFAP2B protein. Tfap2b expression during early mouse tooth development supports the association of TFAP2B mutation and dental anomalies. It is hypothesized that this incidence might have been the result of founder effect. Here we report for the first time that TFAP2B mutation is associated with tooth agenesis, microdontia, supernumerary tooth and root maldevelopment. In addition, we also found that TFAP2B mutations, the common causes of PDA in Caucasian, are not the common cause of PDA in Thai population.

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.

A phenotype of an individual is resulted from an interaction among variants in several genes. Advanced molecular technologies allow us to identify more patients with mutations in more than one genes. Here, we studied a Thai woman with combined clinical features of Marfan (MFS) and Beals (BS) syndromes including frontal bossing, enophthalmos, myopia, the crumpled appearance to the top of the pinnae, midface hypoplasia, high arched palate, dermal stretch marks, aortic enlargement, mitral valve prolapse and regurgitation, aortic root dilatation, and progressive scoliosis. The aortic root enlargement was progressive to a diameter of 7.2 cm requiring an aortic root replacement at the age of 8 years. At her last visit when she was 19 years old, she had moderate aortic regurgitation. Exome sequencing revealed that she carried the c.3159C > G (p.Cys1053Trp) in exon 26 of FBN1 and c.2638G > A (p. Gly880Ser) in exon 20 of FBN2. The variant in FBN1 was de novo, while that in FBN2 was inherited from her unaffected mother. Both genes encode for fibrillins, which are essential for elastic fibers and can form the heterotypic microfibrils. Two defective fibrillins may synergistically worsen cardiovascular manifestations seen in our patient. In this study, we identified the fourth patient with both MFS and BS, carrying mutations in both FBN1 and FBN2.

Patients with Kawasaki disease (KD) who have intravenous immunoglobulin (IVIG) resistance are at increased risk for development of coronary artery abnormalities. Although in Japan several risk scoring systems are able to predict patients with IVIG-resistant (KD), they do not accurately predict non-responders in other regions.The objectives of this study were to determine the predictors of IVIG resistance and coronary artery aneurysm (CAA) and to develop risk scoring systems for predicting IVIG-resistant KD in the Thai population.A total of 217 patients with KD between 2004 and 2014 were retrospectively reviewed. All patients including 116 with complete KD and 101 with incomplete KD were diagnosed and treated with 2 g/kg IVIG.Twenty-six patients (85% male) with IVIG-resistant KD had a reduced platelet count and increased neutrophil-to-lymphocyte ratio compared with those with an IVIG response. Fifty-five patients with CAA eight weeks after diagnosis had a longer duration of fever (≥8 days) and increased platelet count (≥550 × 10KD patients with reduced mean haemoglobin, increased AST level, increased neutrophil-to-lymphocyte ratio and reduced platelet count should be considered for conjunctive therapy such as a corticosteroid in combination with standard treatment. Duration of fever ≥8 days and platelet count ≥550 × 10

Insertion of a ventriculoperitoneal shunt is a common neurosurgical procedure in both adult and paediatric patients. It is one of the most important treatments in cases of hydrocephalus; however, there is a wide range of complications: the most common complication being a shunt infection, and examples of rare complications are shunt migrations and cardiac tamponade. Several reports of distal ventriculoperitoneal shunt migration in different sites, including chest, right ventricle, pulmonary artery, bowel and scrotum were published. But pericardial effusion with cardiac tamponade and its relationship to distal ventriculoperitoneal shunt migration into the pericardial sac has never been reported.

Congenital heart disease (CHD) is a common birth defect affecting approximately 1% of newborns. Great progress has been made in elucidating the genetic aetiology of CHD with advances in genomic technology, which we leveraged in recovering a new pathway affecting heart development in humans previously known to affect heart development in an animal model.Four hundred and sixteen individuals from Thailand and the USA diagnosed with CHD and/or congenital diaphragmatic hernia were evaluated with chromosomal microarray and whole exome sequencing. The DECIPHER Consortium and medical literature were searched for additional patients. Murine hearts from ENU-induced mouse mutants and transgenic mice were evaluated using both episcopic confocal histopathology and troponin I stained sections.Loss of functionOur findings identify Slit-Robo as a significant pathway in human heart development and CHD.

Aortopulmonary window (APW) is a rare congenital heart defect, characterized by a connection between the ascending aorta and the pulmonary trunk before bifurcation. Prenatal diagnosis of APW is essential, as a surgical correction early after birth is required in most cases to prevent congestive heart failure secondary to high pulmonary blood flow. We report a series of three cases of APW that were detected by prenatal echocardiography. The key feature of diagnosis is demonstration of connection between the pulmonary artery and the aorta above the level of the two semilunar valves. Based on our cases and literature review, diagnostic clues for prenatal diagnosis of APW are summarized and proposed.

We report on two daughters and a son of a Thai family who were affected with BWS. Their clinical findings consist of cleft palate, omphalocele, anterior ear creases, indented lesions on the posterior rim of the helix, macroglossia, posterior crossbite, and anterior open bite. The younger daughter and son had newly recognized findings of the BWS including sensorineural hearing loss and supernumerary flexion creases of the fingers. A novel mutation in CDKN1C (c.579delT; p.A193AfsX46) was found in all affected individuals and their mother. This mutation is located in the central highly polymorphic hexanucleotide repeat encoding a proline-alanine series of repeats (PAPA-domain). This domain is involved in MAP kinase phosphorylation. This is for the first time that sensorineural hearing loss and supernumerary flexion creases of the fingers are associated with mutation in CDKN1C.

The aim of this study was to evaluate N-terminal probrain natriuretic peptides (NT-pro-BNP), cardiac troponin T, and creatinine kinase, MB isoenzyme (CK-MB) in the determination of subclinical left ventricular (LV) dysfunction by echocardiography in patients treated with doxorubicin. We performed a cross-sectional case study of systolic, diastolic function and tissue Doppler imaging by echocardiography in children with cancer who received a certain cumulative dose of doxorubicin. Blood levels for NT-pro-BNP, cardiac troponin T, and CK-MB were analyzed within 6 hours of the cardiac study. Of 30 patients, 5 (16.7%) had LV dysfunction with an abnormally high NT-pro-BNP level of 363 ± 78 pg/mL, whereas patients with normal LV function had an NT-pro-BNP level of 148 ± 173 pg/mL (P = 0.012). The NT-pro-BNP level not only inversely correlated with fractional shortening (r = -0.43, P = 0.017) and ejection fraction (r = - 0.45, P = 0.013) but also correlated with mitral deceleration time ( r = 0.41, P = 0.021) and a cumulative dose of doxorubicin (r = 0.44, P = 0.014). For tissue Doppler imaging, NT-pro-BNP correlated with a peak systolic velocity at the myocardial segment (Sm) (r = -0.40, P = 0.027). NT-pro-BNP is a sensitive test and has a moderate relationship with the LV systolic and diastolic function, thus making it a useful cardiac marker for the monitoring of early anthracycline cardiotoxicity.

Background: Cardiac failure remains the major cause of death in beta-thalassemia major (TM). Reduced heart rate variability (HRV) is associated with a higher risk of arrhythmias after myocardial infarction and heart failure. We evaluated HRV in TM patients and its relationship with hemodynamics and echocardiographic parameters during a 6-month follow-up. Methods: Thirty-four TM patients (19 ± 10 yr) and 20 healthy subjects (17 ± 6 yr) were evaluated. Hematologic, biochemical, echocardiographic and HRV parameters were determined at entry and at 6-month follow-up. Time and frequency domain HRV parameters were analyzed from 24-h recorded electrocardiograms. All TM patients received blood transfusion and chelation therapy. Results: Both time and frequency domain HRV parameters were markedly reduced in TM patients, compared to the control. The significantly improved HRV was seen in correlation with higher hemoglobin (Hb) level when compared within TM group at different time point. No correlation was seen between HRV and serum ferritin, reactive oxygen species (ROS) and non-transferrin bound iron (NTBI). Conclusion: HRV is depressed in TM patients. HRV was significantly correlated with Hb level, suggesting that anemia greatly influences the cardiac autonomic balance.

Clinical characteristics, echocardiographic values, and catheterization data of 45 patients with a functional univentricular heart who had a bidirectional Glenn shunt instituted between November 1994 and October 2006 were retrospectively reviewed. Median age at operation was 20 months (range, 9 months to 19 years). Median follow-up time after the bidirectional Glenn operation was 4 years (range, 1 day to 11 years). The early mortality rate was 4/45 (8.9%); overall mortality was 24.4%. Actuarial survival after a bidirectional Glenn shunt was 73% ± 8% at 5 years and 55% ± 17% at 10 years. In multivariate Cox proportional hazards analysis, heterotaxy syndrome and systemic right ventricle were independent predictors of mortality after the bidirectional Glenn shunt. Age at operation, oxygen saturation, previous surgery, a pulsatile Glenn shunt, cardiopulmonary bypass, postoperative pulmonary artery pressure, bilateral superior venae cavae, and Nakata index were not predictive of mortality. The presence of heterotaxy syndrome and systemic right ventricle in patients with a functional univentricular heart should lead to aggressive investigation and management strategies.

Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi in which humans are accidental hosts. It is a febrile illness which is confined to rural Asia and the Western Pacific islands. Severe complications are very rare. We report four cases of acute fulminant myocarditis in children with scrub typhus. This complication led to severe cardiogenic shock and death in two of them. We believe this is the first report of fulminant myocarditis complicating scrub typhus in children.

Moreover, some patients who achieve HIV viral suppression and improved immune function may develop clinical symptoms of immune restoration disease (IRD), which constitutes an increased capacity of infl ammatory reactions against both infectious and non- infectious antigens. Most infectious antigens arise from an unmasking of previously unrecognized infections or a worsening of ongoing opportunis-tic infections.

The major complication of Kawasaki disease is coronary aneurysm which can cause acute coronary disease in early adulthood. There are some reports of coronary artery thrombosis during the period of active Kawasaki disease in infants with giant coronary aneurysm. This report demonstrated a 5-month-old male infant who presented high-grade fever for 7 days. He was treated as urinary tract infection for 6 days before referral. At admission, he had fever, red lips and swelling of both feet, then was diagnosed Kawasaki disease. His EKG showed ST elevation at lead II, III and AVF. His initial echocardiogram revealed coronary dilatation with perivascular brightness; RCA 2.7 mm (Z-score 4.38), LMCA 2.88 mm (Z-score 2.83) and LAD 2.7 mm (Z-score 5.79). There was a clot 2.5 X 2.5 mm in LAD. However, his LV systolic function was normal (EF 76%). His blood test showed low hemoglobin as 8.9 g/dL and MCV as 61.9 fL, high white cell count 20,400/mm3 and platelet count as 606,000/mm3. His initial ESR and CRP elevated at 91 mm/hr and 52 mg/L, respectively. The cardiac enzymes were normal; CKMBmass 2.9 ng/mL (0-3) and troponin-T 0.004 ng/mL (< 0.4). He received IVIG 2.3 g/kg and aspirin 79 mg/kg/day and was closely monitored the vital signs and cardiac enzymes. His fever completely disappeared within 24 hours after treatment, then aspirin was decreased to 6 mg/kg/day. Also, he received intravenous heparin for 4 days, and then was switched to Enoxaparin. He was discharged uneventfully on day 22 of admission. Further blood test confirmed the diagnosis of iron deficiency anemia as follow; serum iron 30 [[Unable to Display Character: ɥ]]g/dL, transferrin-iron binding capacity 446 [[Unable to Display Character: ɥ]]g/dL and transferrin saturation 6.7% (< 16). He received iron supplement for 4 months. The clot in coronary artery gradually decreased in size and finally disappeared in seven months after diagnosis. So, the Enoxaparin was discontinued. He received low-dose aspirin for total course 15 months. His thrombophilia work up was unremarkable. Anemia which is one of the supplementary criteria for atypical Kawasaki disease should be properly evaluated for the cause. The study to find the association between iron deficiency anemia, which was reported as a risk for thromboembolic events, and severity of Kawasaki disease should be further investigated.

ObjectiveWe sought to characterize morphology and to evaluate a strategy of using biventricular repair in patients with a small right ventricle and an unbalanced atrioventricular septal defect.MethodsThirty-eight children with a small right ventricle and an atrioventricular septal defect underwent operative therapy. Thirty-two had biventricular repair, and 6 had single-ventricle palliation. A small right ventricle was defined on the basis of echocardiographic measurements expressed as the atrioventricular valve index (ie, right atrioventricular valve/left atrioventricular valve area) and as the ratio of right ventricular to left ventricular length. Validation of measurements in patients with a small right ventricle and an atrioventricular septal defect was achieved by comparison with balanced case-matched control subjects with atrioventricular septal defects.ResultsChildren with a small right ventricle and an atrioventricular septal defect had a lower atrioventricular valve index (mean, 0.41 ± 0.1 vs 0.52 ± 0.1 [control], P < .0001) and lower right ventricular/left ventricular length ratio (0.78 ± 0.1 vs 0.99 ± 0.17 [control], P < .0001). Children with a small right ventricle undergoing single-ventricle palliation had the smallest right ventricular dimensions. There were 4 operative deaths. Three patients with a small right ventricle and an atrioventricular septal defect who underwent biventricular repair and had an atrioventricular valve index of less than 0.50 required early reoperation for right ventricular inadequacy. A restrictive atrial fenestration was created in 11 infants. Survival at 10 years was 87% for patients undergoing biventricular repair versus 100% for control subjects (P = .042).ConclusionsExtending the use of biventricular repair in properly selected patients with a small right ventricle and an atrioventricular septal defect is feasible. An atrial fenestration improves the physiologic tolerance to repair in selected patients. The use of biventricular repair in children with atrioventricular valve indexes of less than 0.50 requires caution.

BACKGROUND: Ductus arteriosus aneurysm is a rare fetal disorder. CASE: A 35-year-old primigravida had an uneventful antenatal course. Ultrasound examination at 30 weeks of gestation revealed hydramnios. The fetal ductus arteriosus became saccular and dilated with turbulent flow and diameter of 2.5 cm. It was located at the left upper thorax, just distal to the pulmonic valve and extended to the thoracic aorta. A ductus arteriosus aneurysm was diagnosed prenatally. Five days after diagnosis, preterm labor occurred, and dexamethasone and terbutaline were administered. Six hours after initiation of terbutaline, the fetal heart rate suddenly dropped to 90 beats per minute (bpm). A bedside ultrasound examination performed immediately showed profound bradycardia. The aneurysm became a heterogeneous hypoechoic mass with no pulsation, and the fetal heart rate suddenly disappeared. CONCLUSION: Ductus arteriosus aneurysm can be diagnosed prenatally, and terbutaline or dexamethasone may be associated with a risk for rupture.

We present a case of heterotaxy syndrome with right isomerism detected in a twin fetus, with the sonographic findings that established this diagnosis. At 24 weeks' menstrual age, ultrasound detected anomalies in the heart suggestive of heterotaxy syndrome. Intrauterine fetal echocardiography demonstrated that the heart of the affected twin was located on the left side with a normal cardiac axis. The right ventricle was much larger than the left ventricle. The appearance of the mitral valve was dysplastic with restricted motion. The ascending aorta exited from the right ventricle, anterior to, right to, and parallel to the smaller pulmonary trunk, which also arose from the right ventricle. Double-outlet right ventricle (DORV) was clearly demonstrated. Cesarean section was performed at 38 weeks' menstrual age. Both twins were healthy and survived. Postnatal echocardiography and MRI confirmed the prenatal findings. At the age of 4 months, the affected infant had no evidence of cardiac decompensation. This report shows that conventional ultrasound can be used to detect heterotaxy syndrome and that intrauterine fetal echocardiography can delineate the cardiac complex in heterotaxy syndrome. Postnatal surgery with complex Fontan procedures was planned for the affected twin. © 2005 Wiley Periodicals, Inc., J Clin Ultrasound 33:197–200, 2005

Hypoplastic left heart syndrome (HLHS) is a spectrum of fetal conditions associated with severe hypoplasia of the left ventricle and left ventricular outflow tract. The purpose of this series was to focus on the sonographic prenatal features of isolated HLHS. Based on the 5 cases presented here, the prenatal sonographic features of HLHS include small-sized left ventricle, atretic or hypoplastic mitral valves with restricted motion and a small amount of antegrade flow or regurgitation, and hypoplastic ascending aorta. Retrograde flow in the transverse aortic arch strongly suggests inadequate systemic output from the left heart. Tricuspid regurgitation is common and increases the chance for the development of hydrops. Other findings may be helpful, including left ventricular hyperechoic endocardium and increased nuchal translucency at 11-14 weeks. With careful fetal echocardiography, HLHS may be readily observed on a 4-chamber view as either a small or even absent left ventricle.

Background Whereas indications expand and results improve with increasing refinements to the Fontan procedure the overall impact on outcomes related to tricuspid atresia remains suboptimally defined. Methods We reviewed 225 consecutive patients presenting between 1971 and 1999. All patients had classic tricuspid atresia with absent right atrioventricular connection and with D-transposition of the great arteries in 21%, pulmonary outflow obstruction in 75%, and aortic outflow obstruction in 11%. Results Ten patients died before any intervention and 3 patients were lost to follow-up. Palliative procedures (includes 151 with systemic shunt, 27 pulmonary artery banding, 60 venous shunt) were performed in 203 patients, with 44 deaths, 8 patients awaiting Fontan, 12 patients Fontan contraindicated, and 11 patients lost-to-follow-up. A total of 137 patients had the Fontan procedure (9 patients without previous procedures) with 7 early deaths, 11 late deaths, and 3 patients progressing to heart transplantation. Total survival for the cohort was 90% at the age of 1 month, 81% at 1 year, 70% at 10 years, and 60% at 20 years with no significant change over the time period. Independent factors associated with ineligibility or death without Fontan (n = 68, 30%) included earlier birth date, lower birth weight, presence of aortic arch anomaly and greater right ventricular hypoplasia, and no palliative procedure. There were no significant changes in mortality with Fontan over the study time period with survival of 95% at 1 month, 93% at 1year, and 82% at 10 years. Conclusions Improvements in outcomes with tricuspid atresia will require attention to management and risk factors before Fontan.

Objectives: We sought to determine factors that would predict whether a biventricular repair or Norwood procedure pathway would give the best survival in neonates with critical aortic stenosis. Methods: Survival and risk factors were determined with parametric time-dependent event analysis for patients undergoing either the Norwood procedure or biventricular repair, and predicted optimal pathway and survival benefit were derived from multivariable linear regression. Results: From 1994 to 2000, 320 neonates with critical left ventricular outflow obstruction were entered into a prospective multi-institutional study. Patients who died without intervention (n = 19) and those with primary cardiac transplantation (n = 6) were excluded. An initial intended biventricular repair pathway was indicated in 116 patients, with survival of 70% at 5 years. An initial Norwood procedure was performed in 179 patients, with survival of 60% at 5 years. Using predictions from separate multivariable hazard models for survival with each of the 2 pathways, we determined predicted optimal pathway and survival benefit for each patient. Significant independent factors associated with greater survival benefit for the Norwood procedure versus biventricular repair included younger age at entry, lower z-score of the aortic valve and left ventricular length, higher grade of endocardial fibroelastosis, absence of important tricuspid regurgitation, and larger ascending aorta. Predicted survival benefit favored the Norwood procedure in 50% of patients who had biventricular repair, and it favored biventricular repair in 20% of patients who had the Norwood procedure. Conclusions: Morphologic and functional factors can be used to predict optimal pathway and survival benefit in neonates with critical left ventricular outflow obstruction. (J Thorac Cardiovasc Surg 2001;121:10-27)

We report a 10-year-old boy presenting with generalized pitting edema, ascites, abdominal pain, and chronic mucous diarrhea for 4 weeks. He had underlying diseases of hemoglobin E and juvenile rheumatoid arthritis and had been treated with immunosuppressive agents for a long period of time, including prednisolone and methotrexate. After extensive investigations, Strongyloides stercoralis infection, leading to protein-losing enteropathy and eosinophilic granulomatous enterocolitis, was diagnosed. In the present report, we demonstrate early colonoscopic findings, revealing patchy erythema and small raised mucosal nodules with erosions at the cecum. Histopathological study showed open ulceration with cryptitis, intense infiltration of eosinophils and histiocytes with granuloma formation, in which Strongyloides stercoralis larvae were noted.

A retrospective cohort study was conducted on 115 preterm neonates who underwent patent ductus arteriosus ligation after failure of medical treatment, at Chiang Mai University Hospital between January 2003 and December 2010. Two groups were defined: an early surgery group (39.1%) treated with surgical closure within 21 days, and a late surgery group (60.9%) operated on >21 days after birth. There were significant differences between the 2 groups in terms of weight at surgery, birth weight, duration of intubation, ductal size, and preoperative indomethacin usage. The early surgery group had a longer intensive care unit stay, but differences in postoperative chronic lung disease, ductal size, and surfactant use were not significant. Babies with a low birth weight (

Tissue Doppler imaging has been recently used to evaluate ventricular function. Peak oxygen uptake (V•O2peak) has been demonstrated as a predictor for death in adults with repaired tetralogy of Fallot (TOF). The aim of this study was to determine which Doppler parameters correlated with V•O2peak in patients with repaired TOF.Doppler echocardiography, tissue Doppler imaging, and exercise test were performed in 30 patients with TOF after surgical repair. In 30 patients with repaired TOF (median age 14 years, range 9-25 years), 11 patients (37%) were female. Seven patients (median age 12 years) had normal left ventricular diastolic function, whereas the rest of the patients were classified as diastolic dysfunction grade II (median age 15 years; n=15) and III and IV (median age 18 years; n=8). The oxygen uptake at anaerobic threshold (V•O2AT) and peak exercise in patients with left ventricular diastolic dysfunction was significantly lower than that in those with normal diastolic function. Also, V•O2AT and V•O2 peak in patients with diastolic dysfunction grade III and IV were significantly lower than that in those with diastolic dysfunction grade II. Left ventricular early diastolic myocardial velocity was most closely correlated to V•O2peak (r=0.51; P=0.005). Peak early ventricular filling velocity to early diastolic myocardial velocity ratio was significantly correlated with V•O2peak (r=-0.50; P=0.006).Left ventricular diastolic dysfunction is correlated with V•O2peak. Left ventricular diastolic function should be a routine echocardiographic assessment in patients with repaired TOF.

Highlight the management of a critically ill premature hydropic baby with refractory atrial flutter (AF) and successful outcome without neurologic sequel at 1 year of follow-up.A 23-year-old pregnant woman, G1PO, presented with fetal tachycardia at 32 weeks.Ultrasound revealed a hydropic fetus with fetal atrial rate (FHR) of 440 bpm and A:V block of 2:1. Transplacental therapy resulted in a temporary response with the combination of digoxin and flecainide, and subsequently digoxin plus sotalol. Termination of pregnancy at 34 weeks was performed for postnatal treatment, giving birth to a premature hydropic baby, weighing 3320 grams. At birth flecainide failed to control the AF Therefore, intravenous adenosine was started and successful conversion to normal sinus rhythm was temporally achieved. Finally, conversion to normal sinus rhythm with amiodarone plus digoxin was satisfactorily achieved and then long-term control with only oral flecainide. The hydropic signs gradually disappeared without any significant sequelae. The baby was healthy at one year of follow-up without any neurological sequelae.This case may be evidence that combined therapy with amiodarone and digoxin is probably effective in treatment of refractory AF with hydropic changes, at least in some cases.

Kawasaki disease (KD) is associated with a high incidence of coronary artery aneurysms in untreated children. Treatment with intravenous immunoglobulin (IVIG) within the 1st 10 days of illness reduces by approximately fivefold the prevalence of coronary artery abnormalities (CAA). Data regarding delayed diagnosis of KD in Thailand have not been reported in the literature.To determine the prevalence, risk factors and outcome of delayed diagnosis of KD in Thai patients.We retrospectively reviewed the medical records of patients at Chiang Mai University Hospital diagnosed as KD during 2000-2008. Patients were classified into two groups: Group I were diagnosed ≤10 days of fever and Group II were diagnosed10 days of fever.Of 170 patients, 150 were in Group I [mean (SD) fever 7 (1·45) d] and 20 (11·7%) in Group II [mean (SD) fever 15 (4) d]. There were no statistical differences between the two groups in age, gender, number of KD clinical manifestations or laboratory results, except that Group II were of lower weight (p = 0·01). Group II were younger (p = 0·09) and had more incomplete criteria (p = 0·09) but the differences were not statistically significant. Group II had a higher incidence of CAA (75% vs 19%) (p0·001), more severe CAA and more resistant cases (31·2% vs 9·5%) (p = 0·04).Patients with delayed diagnosis of KD have a higher risk of developing CAA and of a more severe outcome for coronary artery disease. Education is needed to make healthcare providers and physicians more aware of KD, especially in small children or those with incomplete KD.

Heart rate variability (HRV) has been used as a reliable method to detect cardiac autonomic nervous system activity. Peak oxygen uptake (VO(2) peak) has been a predictor of death for adults with repaired tetralogy of Fallot (TOF). This study investigated the correlation between HRV and exercise capacity in 30 patients with TOF after surgery for total correction. The median age of the patients was 14 years (range, 9-25 years), and the median follow-up period was 11.6 months (range, 5.3-20.2 months). Low- and high-frequency-domain HRV significantly correlated with VO(2) peak (r = 0.56, P = 0.001 and r = 0.44, P = 0.02, respectively). After the 1-year follow-up evaluation, VO(2) peak and HRV analysis did not differ from those at entry to the study. However, low- and high-frequency-domain HRV still correlated significantly with VO(2) peak (r = 0.43, P = 0.03 and r = 0.52, P = 0.007, respectively). Left ventricular early diastolic myocardial velocity was most closely correlated with the VO(2) peak (r = 0.51, P = 0.005). Impaired cardiovascular autonomic control and left ventricular diastolic dysfunction may be responsible for exercise intolerance in patients with repaired TOF. Long-term follow-up evaluation with exercise testing and 24-h Holter monitoring are warranted.

Acro-cardio-facial syndrome (ACFS) is a rare autosomal recessive congenital malformation syndrome; consistent features include ectrodactyly, cleft lip/palate with minor facial anomalies, genital abnormalities, mental retardation, and growth retardation. Five cases have been reported. We report on a new patient with ACFS syndrome. In addition to the characteristic features of ACFS, the reported patient also has mild scoliosis, hemivertebrae and subclinical hyperthyroidism. These additional features may expand the phenotypic spectrum of the syndrome.

Tissue Doppler imaging has been recently used to evaluate ventricular function in patients with beta thalassemia. In clinical practice, serum ferritin is commonly used to assess the severity of iron overload. The aim of this study was to determine which Doppler findings correlated with serum ferritin.Thirty-one pediatric patients with transfusion-dependent beta thalassemia with normal LVFS were evaluated. Seven patients with serum ferritin2500 ng/ mL, 13 patients with serum ferritin 2500-5000 ng/mL, and 11 patients with serum ferritin5000 ng/mL were studied. Diastolic dysfunction was absent in all patients with serum ferritin2500 ng/mL, and was present in all patients with serum ferritin5000 ng/mL. Deceleration time (DT) has a significant correlation with serum ferritin (r = -0.59, p0.0001). Difference of pulmonary vein atrial reversal flow and mitral valve A wave duration (PVAR - MVA) and early ventricular filling velocity to early diastolic myocardial velocity ratio (E/Em) significantly correlated with serum ferritin (r = 0.49, p = 0.006; r = 0.56, p = 0.001, respectively).Decreased DT, increased PVAR-MVA duration, and increased E/Em ratio reliably reflected severe iron overload in pediatric patients with beta thalassemia. Systolic and diastolic LV function is preserved in patients who have serum ferritin2500 ng/mL.

Four fetuses were diagnosed antenatally with double outlet of right ventricle (DORV) at 17, 20, 26, and 28 weeks' gestation, respectively, using 2-dimensional sonography. Chromosome study was normal in all 4 cases, and there were no extracardiac abnormalities. The sonographic diagnoses were based on the following findings: (1) arising of the 2 great vessels predominantly from the right ventricle; (2) the presence of bilateral coni; and (3) parallel direction of the 2 vessels rather than the normal perpendicular course. Two cases were terminated electively with postnatal autopsy confirmation; the other 2 cases were closely monitored throughout pregnancy and underwent normal vaginal delivery at term and subsequent surgical correction with good outcome. In conclusion, DORV can be readily diagnosed in utero by checking outflow tract even without 3-dimensional sonography and in the absence of obvious risk for congenital heart defects.

To determine factors influencing immediate and medium-term results of Pulmonary Balloon Valvuloplasty (PBV) for pulmonary valve stenosis.Between 1995 and 2001, the authors carried out PBV in 25 consecutive patients. Two treatment outcomes including immediate and medium-term results were analyzed. The immediate results were classified into two groups based on the pulmonary systolic pressure gradient (PG) immediately after dilation: group 1 with a PGor = 35 mmHg and group II with a PG35 mmHg. At medium-term follow-up of 6 to 60 months, echocardiographic evaluations were analyzed and divided into two groups: group A with a PGor = 25 mmHg and group B with a PG25 mmHg. Demographic characteristics and hemodynamic parameters of immediate and medium-term results were compared and analyzed.Immediately after PBV the right ventricular systolic pressure (RVSP) decreased from 115.3 +/- 37.6 mmHg to 67.0 +/- 28.5 mmHg (p0.001). The pulmonary systolic pressure gradient decreased from 90.4 +/- 37.9 mmHg to 39.3 +/- 25.6 mmHg (p0.001). Nine of the 25 patients (group 11; 36%), with incomplete immediate relief of the obstruction, had more symptoms, a higher baseline PG, higher right atrial pressure, higher RVSP, and a higher systolic pressure ratio. Six of the 25 patients (group B; 24%), with suboptimal medium-term results, had a higher right ventricular voltage on the electrocardiogram, higher pre-dilation PG, and higher RVSP.Successful medium-term outcomes following pulmonary balloon valvuloplasty were achieved in 76% of the patients, with a greater success rate (91%) in patients with a lower right ventricular voltage electrocardiogram (R wave amplitude in V1)or = 21 mm, a prevalvuloplasty systolic gradientor = 90 mmHg, and right ventricular systolic pressureor = 125 mmHg.

The incidence of Kawasaki disease (KD) in Thailand has never been studied before. We reviewed the data from the National Registry of Thai Children who had KD between 1998-2002 to evaluate the incidence of KD and cases resistant to treatment with intravenous immunoglobulin (IVIG). Resistance to IVIG was defined as remaining febrile at least 48 hours after initial IVIG therapy. There were 710 KD patients in the registry. The incidence of KD was from 2.14 to 3.43 cases per 100,000 children aged 0-5 years. During the acute phase 15.6% of 435 patients were considered as resistant cases. Resistant cases of KD in Thai children are quite common (15.6%) even after IVIG treatment. We found that patients who had high white blood cell counts (16,500 cells/mm3) had a higher likelihood of being resistant.

Thai children who need cardiac surgery are often put on a waiting list. The waiting time and mortality during waiting have not been previously systematically studied.A cooperative study was conducted at King Chulalongkorn Memorial hospital (Chula), Children hospital (CH), and Chiang Mai University hospital (CMU). The status of children who were referred for cardiac surgery at these hospitals in the year 1999-2000 (Chula and CMU) and the year 2000 (CH) were analyzed by Kaplan-Meier survival curve. The patients who lost to follow up and could not be contacted were censored at the time of last clinic visit. Log-Rank test was used to compare the survival curve and waiting time between three hospitals.The averaged annual referrals for cardiac surgery at the three hospitals were 846 cases (205 for Chula, 462 for CH and 179 for CMU). Mean age was 4.3 +/- 4.2 years and 51% were male. Follow up data were complete in 96.3%. Surgical procedures were correction of simple shunt lesions (ASD, VSD, AV canal) in 33.9%, close heart surgery (PDA ligation, coarctation repair, BT shunt) in 29.9%, total repair TOF in 19.6%, complex surgery in neonate and infants (arterial switch, TAPVR repair, Norwood procedure, truncus and interrupted aortic arch repair) in 4.2% and others in 12.3%. Median waiting time was 195 days and was significantly different between the three hospitals (p0.01). Mortality while waiting were approximately 5% at 2 years at Chula and CH, which was significantly higher than CMU (0%, p = 0.02). Further analysis revealed difference in age (lower Chula than CH than CMU) and types of surgery (more complex at Chula and CH) which may be the causes for difference in the mortality observed.Waiting time for cardiac surgery for children in Thailand is long and should be viewed as a problem in public health policy. Optimal waiting time at each hospital may not have to be the same, depending on the type and severity of the disease seen at each particular center Attempt should be made to solve this problem at the national level.

The objective of this report was to demonstrate prenatal sonographic features of congenital ductus arteriosus aneurysm (DAA), a rare, but possibly fatal abnormality. It is characterized by a saccular or fusiform dilatation of the ductus arteriosus. The majority of affected neonates are clinically asymptomatic and tend to progressively diminish in size of DAA and spontaneous closure. However, serious complications can occur during waiting periods, including spontaneous rupture or thromboembolism.A 35 year-old Thai woman, G2P1, underwent ultrasound examination at 34 weeks' gestation. Fetal echocardiography revealed markedly enlarged and tortuous ductus arteriosus with saccular dilation at the distal end, just before joining the descending aorta. The cross-sectional diameter of the saccular portion of the ductus arteriosus was 10 mm. The active female baby was vaginally delivered at 34 weeks' gestation, weighing 1050 grams. Postnatal echocardiography confirmed the prenatal findings. The DAA was gradually decreased in size and finally spontaneously closed without medical or surgical intervention.