Search

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.

Cardiac T2* MRI is used as a gold standard for cardiac iron quantification in patients with transfusion-dependent thalassemia (TDT). We hypothesized that left ventricular (LV) diastolic dysfunction would reflect the severity of iron overload and can serve as an early detection of cardiac iron deposits. A study was conducted on all patients with TDT. Hemoglobin, serum ferritin and non-transferrin bound iron, together with a complete echocardiography and cardiac T2* MRI, were performed on all patients. Seventy-seven patients with TDT were enrolled (median age 14 years). In the patient group with a mean serum ferritin of 2500 ng/mL during the past 12 months, there were more patients with severe cardiac iron deposits than in the group with a mean serum ferritin of ≤ 2500 ng/mL. Diastolic dysfunction was absent in all patients with a serum ferritin of 1000 ng/mL. All patients with cardiac T2* ≤ 20 ms had grade III LV diastolic dysfunction. However, twenty-one percent of patients with cardiac T2* 20 ms had LV diastolic dysfunction. The differences observed in pulmonary vein atrial reversal duration and mitral A-wave (PVAR-MVA) duration ≥ - 1 ms and an E/E' ratio ≥ 11 were proven to be the associated factors with the cardiac T2* ≤ 20 ms. Increased PVAR-MVA duration and increased E/E' ratio reliably reflected a severe iron overload, according to a cardiac T2* in patients with TDT. LV diastolic dysfunction can occur prior to severe cardiac iron deposition. Tissue Doppler echocardiography has the potential for the early detection of cardiac involvement in patients with TDT .

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 Wilms tumor is the most common renal malignancy in childhood. It occurs primarily between the ages of 2 and 5 years. The usual manifestations are abdominal mass, hypertension, and hematuria. The case presented here had an unusual presentation, with dilated cardiomyopathy and hypertension secondary to the Wilms tumor. Case summary A 3-year-old boy presented with a 5-d history of irritability, poor appetite, and respiratory distress. His presenting clinical symptoms were dyspnea, tachycardia, hypertension, and a palpable abdominal mass at the left upper quadrant. His troponin T and pro-B-type natriuretic peptide levels were elevated. Echocardiography demonstrated a dilated hypokinetic left ventricle with an ejection fraction of 29%, and a suspected left renal mass. Computed tomography scan revealed a left renal mass and multiple lung nodules. The definitive diagnosis of Wilms tumor was confirmed histologically. The patient was administered neoadjuvant chemotherapy and underwent radical nephrectomy. After surgery, radiotherapy was administered, and the adjuvant chemotherapy was continued. The blood pressure and left ventricular function normalized after the treatments. Conclusion Abdominal mass, dilated cardiomyopathy and hypertension can indicate Wilms tumor in pediatric patients. Chemotherapy and tumor removal achieve successful treatment.

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

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: Iron overload cardiomyopathy is the most common cause of death in patients with transfusion-dependent thalassemia. Aim: The aim of this study was to determine the efficacy of carvedilol treatment in patients with transfusion-dependent thalassemia who had left ventricular diastolic dysfunction. Methods: Eighteen patients with transfusion-dependent thalassemia who had left ventricular diastolic dysfunction were enrolled. All patients had normal left ventricular systolic function and were given carvedilol with the target dose of 0.8 mg/kg/day. Ventricular function and the level of cardiac iron were assessed by echocardiography and magnetic resonance imaging at 0, 3, and 6 months. Results: The median age of the patients was 19 years (range 13–25 years). Four patients had severe left ventricular Grade III diastolic dysfunction and fourteen patients had Grade II diastolic dysfunction. The grade of left ventricular diastolic dysfunction was improved at 3 months after the carvedilol treatment. The Doppler parameters, including pulmonary vein atrial reversal velocity, pulmonary vein atrial reversal duration, and the difference of pulmonary vein atrial reversal and the mitral valve atrial contraction wave duration at 3 months after the carvedilol treatment, were significantly lower than these parameters before the treatment. Conclusions: Among patients with transfusion-dependent thalassemia who had left ventricular diastolic dysfunction without systolic dysfunction, treatment with carvedilol for 3 months was associated with improvement in Doppler parameters of left ventricular diastolic function. However, this finding and its clinical significance need to be confirmed in further double-blind controlled studies.

Journal of Associated Medical Sciences, 53, 3, 43-54

Background: In low- and middle-income countries (LMIC), haemodynamically significant patent ductus arteriosus (hsPDA) is treated with oral indomethacin (IDC) and ibuprofen (IB) instead of intravenous formulations. No significant differences in efficacy have been reported. However, previous studies had small numbers of VLBW infants (

Autism spectrum disorder (ASD) has a strong genetic basis, although the genetics of autism is complex and it is unclear. Genetic testing such as microarray or sequencing was widely used to identify autism markers, but they are unsuccessful in several cases. The objective of this study is to identify causative variants of autism in two Thai families by using whole-exome sequencing technique. Whole-exome sequencing was performed with autism-affected children from two unrelated families. Each sample was sequenced on SOLiD 5500xl Genetic Analyzer system followed by combined bioinformatics pipeline including annotation and filtering process to identify candidate variants. Candidate variants were validated, and the segregation study with other family members was performed using Sanger sequencing. This study identified a possible causative variant for ASD, c.2951G>A, in the FGD6 gene. We demonstrated the potential for ASD genetic variants associated with ASD using whole-exome sequencing and a bioinformatics filtering procedure. These techniques could be useful in identifying possible causative ASD variants, especially in cases in which variants cannot be identified by other techniques.

Autism spectrum disorder (ASD) has a strong genetic basis, although the genetics of autism is complex and it is unclear. Genetic testing such as microarray or sequencing was widely used to identify autism markers, but they are unsuccessful in several cases. The objective of this study is to identify causative variants of autism in two Thai families by using whole-exome sequencing technique. Whole-exome sequencing was performed with autism-affected children from two unrelated families. Each sample was sequenced on SOLiD 5500xl Genetic Analyzer system followed by combined bioinformatics pipeline including annotation and filtering process to identify candidate variants. Candidate variants were validated, and the segregation study with other family members was performed using Sanger sequencing. This study identified a possible causative variant for ASD, c.2951G>A, in the FGD6 gene. We demonstrated the potential for ASD genetic variants associated with ASD using whole-exome sequencing and a bioinformatics filtering procedure. These techniques could be useful in identifying possible causative ASD variants, especially in cases in which variants cannot be identified by other techniques.

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.

Background. Congenital heart block is characterized by blockage of electrical impulses from the atrioventricular node (AV node) to the ventricles. This blockage can be caused by ion channel impairment that is the result of genetic variation. This study aimed to investigate the possible causative variants in a Thai family with complete heart block by using whole exome sequencing.Methods. Genomic DNA was collected from a family consisting of five family members in three generations in which one of three children in generation III had complete heart block. Whole exome sequencing was performed on one complete heart block affected child and one unaffected sibling. Bioinformatics was used to identify annotated and filtered variants. Candidate variants were validated and the segregation analysis of other family members was performed.Results. This study identified compound heterozygous variants, c.101G>A and c.3832G>A, in theSCN5Agene and c.28730C>T in theTTNgene.Conclusions. Compound heterozygous variants in theSCN5Agene were found in the complete heart block affected child but these two variants were found only in the this affected sibling and were not found in other unaffected family members. Hence, these variants in theSCN5Agene were the most possible disease-causing variants in this family.

Short stature is one of the most common endocrinopathies in transfusion-dependent thalassemia (TDT). This study aimed to determine the longitudinal pattern of growth in pediatric patients with TDT and study the relationship between growth and hemoglobin level, serum ferritin level/iron overload parameters, and other clinical factors. The interval height-for-age Z-scores (HAZ) of 50 patients with TDT, of a mean age of 13.3±2.8 years, were analyzed using linear mixed model analysis. Nineteen patients (38%) had short stature with HAZ≤-2.0. The prevalence of short stature increased with age. The estimated mean HAZ decreased by 0.19 SD per year from the age of 5 years until approximately 14 years (95% confidence interval [CI], -0.22 to -0.16, P

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.

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.

Background Iron-overload cardiomyopathy is a major cause of death in thalassemia patients due to the lack of an early detection strategy. Although cardiac magnetic resonance (CMR) T2* is used for early detection of cardiac iron accumulation, its availability is limited. Heart rate variability (HRV) has been used to evaluate cardiac autonomic function and found to be depressed in thalassemia. However, its direct correlation with cardiac iron accumulation has never been investigated. We investigated whether HRV can be used as an alternative indicator for early identification of cardiac iron deposition in thalassemia patients. Methods Ninety-nine non-transfusion dependent thalassemia patients (23.00 (17.00, 32.75) years, 35 male) were enrolled. The correlation between HRV recorded using 24-hour Holter monitoring and non-transferrin bound iron (NTBI), hemoglobin (Hb), serum ferritin, LV ejection fraction (LVEF), and CMR-T2* were determined. Results The median NTBI value was 3.15 (1.11, 6.59) μM. Both time and frequency domains of HRV showed a significant correlation with the NTBI level, supporting HRV as a marker of iron overload. Moreover, the LF/HF ratio showed a significant correlation with CMR-T2* with the receiver operating characteristic (ROC) curve of 0.684±0.063, suggesting that it could represent the cardiac iron deposit in thalassemia patients. HRV was also significantly correlated with serum ferritin and Hb. Conclusions This novel finding regarding the correlation between HRV and CMR-T2* indicates that HRV could be a potential marker in identifying early cardiac iron deposition prior to the development of LV dysfunction, and may be used as an alternative to CMR-T2* for screening cardiac iron status in thalassemia patients.

Pulmonary hypertension is a major cardiac complication in non-transfusion-dependent thalassemia (NTDT). Several clinical and laboratory parameters, including iron overload, have been shown to have a positive correlation with the incidence of pulmonary hypertension. Non-transferrin-bound iron (NTBI) is a form of free-plasma iron that is a good indicator of iron overload.The aim of this study was to determine the prevalence of pulmonary hypertension in patients with NTDT and to investigate its correlation with the clinical parameters, liver iron concentration (LIC) and NTBI.Patients with NTDT were evaluated using echocardiography, and magnetic resonance imaging for cardiac T2* and LIC. Pulmonary hypertension was defined as peak tricuspid regurgitation velocity ≥2.9 m/s measured using trans-thoracic echocardiography. Clinical parameters and the status of iron overload as determined by LIC, serum ferritin, and NTBI level were evaluated for their association with pulmonary hypertension.Of 76 NTDT patients, mean age 23.7 ± 8.5 years, seven patients (9.2%) had pulmonary hypertension. Previous splenectomy (71.4 vs. 24.6%, P-value 0.019), higher cumulative red blood cell (RBC) transfusions (received ≥10 RBC transfusions 85.7 vs. 33.3%, P-value 0.011), higher nucleated RBCs (353 ± 287 vs. 63 ± 160/100 white blood cells, P-value0.001), and a high NTBI level (5.7 ± 3.0 vs. 3.3 ± 2.8 µmol/l, P-value 0.034) were associated with pulmonary hypertension. There was no significant correlation between LIC or serum ferritin and pulmonary hypertension.Pulmonary hypertension in NTDT is common, and is associated with splenectomy and its related factors. NTBI level shows a significant correlation with pulmonary hypertension.

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.

Background: Vibratory innocent murmur is the most common precordial innocent murmur in children. The mechanism of vibratory innocent murmur is still unclear. Objectives: The aim of this study is to learn the mechanism of the vibratory innocent murmur. Patients and Methods: The prospective cross-sectional study was conducted using 32 children who had the vibratory innocent murmur (cases) in Chiang Mai University Hospital and 27 normal healthy children (controls). Two-dimension, Doppler, and tissue Doppler echocardiography were performed on each subject to examine the difference between cases and controls. Results: The left ventricular false tendon was present in 84% of cases and 22% of controls (P < 0.001). Left ventricular outflow tract velocity was significantly higher in cases than in controls (P < 0.001). Early diastolic myocardial velocity at the base of the interventricular septum was lower in cases with false tendon than those without false tendon (P = 0.048). No significant difference was found regarding ascending aorta diameter, cardiac output and ejection fraction between the two groups. Left ventricular diastolic function was normal in all cases and controls. Conclusions: The vibratory innocent murmur is associated with the presence of left ventricular false tendon and higher left ventricular outflow tract velocity. The presence of the left ventricular false tendon was somewhat associated with decreased early diastolic myocardial velocity. Normal left ventricular systolic and diastolic function can be used as a reassurance in cases with the vibratory innocent murmur.

In congenital heart defects where the morphologic right ventricle (RV) supports the systemic circulation, RV failure is common yet develops gradually. We hypothesized that patients who are asymptomatic may have unrecognized RV dysfunction.Conventional and Doppler tissue/strain echocardiography were performed on consecutive patients with asymptomatic systemic RV caused by congenitally corrected transposition of the great arteries (ccTGA) and on age-matched control subjects. RV index of myocardial performance was measured using conventional echocardiography. Longitudinal tissue velocities, strain rate, and strain of the basal RV free wall were measured using Doppler tissue/strain echocardiography and compared with nonsystemic RV of the control subjects.Mean age was 39.5 +/- 14.6 (n = 13) and 36 +/- 24 (n = 10) years for ccTGA and control groups, respectively. Mean RV index of myocardial performance was higher in patients with ccTGA than in control subjects (0.66 +/- 0.25 vs 0.28 +/- 0.12, P.001). Mean RV tissue displacement (10.8 +/- 4.5 vs 20.3 +/- 3.9 mm, P.0001), peak systolic strain rate (-1.16 +/- 0.3 vs -2.23 +/- 0.9 s(-1), P = .005), and peak systolic strain (-17.3 +/- 8.0 vs -30.6 +/- 11.0%, P = .008) were significantly lower in patients with ccTGA compared with control subjects, respectively.Patients with asymptomatic ccTGA have quantifiable RV dysfunction by echocardiography.

Evaluation of pulmonary outflow obstruction has focused on maximum instantaneous gradient (MIG). However, experience suggests that outpatient Doppler MIG often overstates the degree of stenosis. In this study of 132 patients with complex pulmonary stenosis, the mean Doppler gradient showed superior correlation and agreement with invasive peak-to-peak gradient (PPG) (r = 0.91, bias = -6 mm Hg). Agreement between mean gradient and PPG remained excellent for patients with prosthetic conduits (bias = -4 mm Hg). When PPG was 50 mm Hg more, both mean Doppler gradient and MIG corrected for prevalve velocity provided reasonable estimates of PPG (bias = -13 and +17 mm Hg, respectively). Uncorrected MIG remained significantly greater than PPG (bias = +27 mm Hg). Outpatient MIG consistently overstated subsequent PPG. In unselected patients with conduits or with PPG of 50 mm Hg or less, mean Doppler gradient provided the best prediction of PPG. These data provide a strong argument for the routine use of mean gradients in complex pulmonary stenosis.

A 21-year-old adult patient with Tetralogy of Fallot presented acutely unwell with a 3-month history of general malaise following dental treatment. Following initial complete repair, he subsequently underwent two right ventricular outflow tract reconstructions with conduits. On admission, transthoracic echocardiography and peripheral blood cultures were suggestive of streptococcal endocarditis. Sequential computed tomography pulmonary angiography demonstrated peripheral emboli with progressive central pulmonary artery filling defects suggestive of thrombi and potential vegetations (Fig 1a and b). Urgent surgery was performed for uncontrolled sepsis and increasing hypoxia. Peri-operative transesophageal echocardiogram confirmed previous findings (Fig 1c; Supplementary Video 1). Having resected the conduit, we performed a peripheral pulmonary embolectomy and resected an abundance of the infected material from the pulmonary arterial tree under low-flow hypothermia; we then proceeded with a jugular venous valved conduit (Contegra®, Medtronic Inc, Minneapolis, Minnesota, United States of America) replacement and tricuspid valve annuloplasty. He made a slow but steady recovery and was discharged home in good health

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.

A previously healthy 3-year-old boy presented with high-grade fever, dyspnoea, alteration of consciousness, tachycardia and shock. A few erythematous macules and papules were seen on his palms and soles. Echocardiogram showed poor left ventricular contraction. Cardiac enzymes and pro-B-type natriuretic peptide were elevated. Milrinone, low-dose dopamine and intravenous immunoglobulin were administered. The patient recovered after 5 days without cardiac or neurological sequelae. The serological results showed a four-fold rise of enterovirus 71. In children with severe EV71 infection, early recognition of cardiopulmonary involvement and aggressive treatment are crucial to successful management.

To evaluate thyroid function in children with Down's syndrome, and to ascertain the presence of a relationship between overt thyroid diseases and congenital anomalies.One hundred and forty Down's syndrome patients, aged from 3 days to 13 years 9 months, were evaluated for karyotype, thyroid functions and the coexistence of congenital anomalies.Trisomy 21 was found in the majority of cases (95.7%). Fifty-six patients (40%) had abnormal thyroid functions: 53 (37.9%) hypothyroidism and 3 (2.1%) hyperthyroidism. Ten patients (7.1%) were diagnosed with overt thyroid disease: congenital hypothyroidism 3.6%, acquired hypothyroidism associated autoimmune thyroiditis 1.4% and hyperthyroidism 2.1%. None of the patients with congenital hypothyroidism had athyreosis or ectopic thyroid gland. Sub-clinical hypothyroidism accounted for 32.9% of all cases; 10.7% showed a spontaneous decrease to normal TSH levels and 13.6% had persistently elevated TSH levels with the median follow-up time of 6 and 12 months, respectively. Congenital heart disease, gastrointestinal anomalies and hematological disease were found in 73.6, 10 and 3.6 percent of patients, respectively. There was no statistical correlation between the coexistence of cardiovascular or gastrointestinal disease in Down's syndrome patients with overt thyroid diseases or sub-clinical hypothyroidism to those having normal thyroid functions.Sub-clinical hypothyroidism was the most common thyroid abnormality in children with Down's syndrome. A longitudinal and timely-scheduled evaluation of thyroid function is needed to establish the natural course of this abnormality and the proper management guideline.

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.

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.

Maximum instantaneous Doppler gradient has been the primary variable used to assess severity of pulmonary valve stenosis. However, recent observations suggest that outpatient maximum Doppler gradient often overstates clinical severity, as measured by catheter peak-to-peak gradient (PPG). This study sought to determine which outpatient Doppler gradient was most predictive of subsequently measured PPG. Ninety patients were included. Outpatient mean Doppler gradient showed the best correlation and agreement with the catheter PPG (r = 0.82, bias = -5 mm Hg). Maximum Doppler gradients, even when corrected for proximal velocity, consistently overestimated the PPG (bias = +21-26 mm Hg). Outpatient mean gradient was most predictive of subsequent PPG and should be used to determine whether to intervene for patients with isolated pulmonary valve stenosis. Use of only the maximum Doppler gradient to assess pulmonary valve stenosis will lead to a systematic overstatement of the severity of the stenosis.

Cardiac complications contribute significantly to morbidity and mortality in HIV-infected children. There have been few reports of cardiac manifestations in HIV-infected children in developing countries. The aims of this study were to evaluate the clinical manifestations and echocardiographic findings in Thai children with HIV infection and determine the clinical predictors of left ventricular dysfunction and pulmonary hypertension. We retrospectively reviewed the medical records of 27 infants infected with HIV perinatally who presented with cardiovascular problems at a tertiary care hospital between 1995 and 2000. The mean age at initial cardiac evaluation was 36 months (range 8-65). Signs and symptoms included dyspnoea in all cases, oedema in 12 (44%), finger clubbing in 11 (41%), cyanosis in 6 (22%) and S(3) gallop in 8 (30%). Echocardiographic abnormalities included pericardial effusion in 12 (44 %), right ventricular dilatation in 12 (44%), pulmonary hypertension in 11 (41%), diminished left ventricular fractional shortening in 10 (37%), left ventricular dilatation in 9 (33%) and combined ventricular dilatation in 2 (7%). Left ventricular dysfunction did not correlate with HIV CDC classification, age, nutritional status or clinical signs and symptoms.

Infants with Kawasaki disease (KD) are at increased risk of having coronary artery abnormalities (CAA). The purpose of this study was to evaluate the clinical features of KD in infants and compare these with findings in older children to determine the risk factors for CAA in infants. All children with KD admitted to a tertiary care hospital between January 1993 and April 2003 were studied retrospectively. Of a total of 51 patients included in the study, 22 (43%) were

Isolated primary chylopericardium is a rare entity with an obscure etiology. The authors report a 10-week-old male infant presenting with tachypnea and enlarged cardiac silhouette. Echocardiography revealed a large pericardial effusion. A specific diagnosis of chylopericardium was made by pericardiocentesis and analysis of the fluid. Despite the pericardial tube drainage and medium-chain triglyceride diet, pericardial effusion reaccumulated. Ligation of the thoracic duct with the establishment of a pleuropericardial window was performed through a left thoracotomy. Follow-up echocardiograms have shown no reaccumulation of the pericardial fluid.

The authors report a pseudoaneurysm in a 2-year-old boy presenting with fever, increasing cyanosis and right upper lung shadowing on a chest radiograph at six weeks following modified Blalock-Taussig shunt surgery. Echocardiography and a CT scan of the chest revealed a large pseudoaneurysm originating from the right subclavian artery at the proximal insertion of modified Blalock-Taussig shunt. The patient underwent aneurysmal resection, Blalock-Taussig shunt removal, right subclavian artery ligation and the creation of a central shunt between the ascending aorta and main pulmonary artery. Unfortunately, the patient died 3 hours after the operation.

Background 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. Methods 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. Results Loss of function ROBO1 variants were identified in three families; each proband had a ventricular septal defect, and one proband had tetralogy of Fallot. Additionally, a microdeletion in an individual with CHD was found in the medical literature. Mouse models showed perturbation of the Slit-Robo signalling pathway, causing septation and outflow tract defects and craniofacial anomalies. Two probands had variable facial features consistent with the mouse model. Conclusion Our findings identify Slit-Robo as a significant pathway in human heart development and CHD.