Clinical course of fetal congenital atrioventricular block in the Japanese population: a multicentre experience.

OBJECTIVES: To elucidate the prenatal and postnatal course of fetal congenital atrioventricular block (CAVB) during the past decade in the Japanese population. DESIGN: Retrospective multicentre study. All fetuses with CAVB in 10 Japanese institutions in the period from January 1990 to August 2001 were included. PATIENTS: Of the 48 fetuses with CAVB, 17 had a congenital heart defect (CHD) (14 with left atrial isomerism) and 31 had a structurally normal heart (22 with positive maternal autoantibodies). Gestational age at diagnosis was 15 to 38 (median 26) weeks. RESULTS: Of the 17 fetuses with a CHD, three were aborted, one died before birth, and eight died after birth (three in the neonatal period and five after the neonatal period). Of the 31 fetuses without a CHD, two died before birth and two died after birth. CHD (p = 0.005) and the presence of fetal hydrops (p = 0.05) were significant risk factors for death. However, fetal ventricular and atrial heart rates, gestational age at delivery, and birth weight were not related to death. Transplacental medication of sympathomimetics increased the fetal heart rate in five of eight fetuses treated. Dexamethasone did not improve the degree of heart block in any of the six fetuses treated. Postnatally, pacemakers were implanted in 30 of 40 babies. Four fetuses with maternal autoantibodies had decreased cardiac function. CONCLUSIONS: CHD and fetal hydrops are risk factors for prenatal and postnatal death. The fetal ventricular rate of 55 beats/min did not appear to be a threshold value by which to predict fetal hydrops. Patients with CAVB should be subjected to close long term follow up to check for the need for pacemaker implantation or for late onset cardiac dysfunction.

Prenatal diagnosis of sustained bradycardia with 1 : 1 atrioventricular conduction.

OBJECTIVES: The aims of this study were to elucidate the clinical course of fetal bradycardia with 1 : 1 atrioventricular conduction, and to discuss the optimal management of affected fetuses in the second and third trimesters of pregnancy. METHODS: The hospital records of five fetuses with the diagnosis of bradycardia (100 bpm) with 1 : 1 atrioventricular conduction between 1981 and 2000 in our institution were reviewed. Atrioventricular conduction was evaluated by simultaneous M-mode echocardiographic tracing of the atria and the ventricles. RESULTS: The gestational ages at referral ranged from 19 to 36 (median, 25) weeks, and fetal heart rates ranged from 60 to 80 (median, 80) bpm. Postnatal electrocardiography revealed sinus bradycardia in four (two of which were siblings) of the five cases, and junctional rhythm in the remaining case. Two fetuses with congenital heart defects (CHDs) were delivered by Cesarean section but died postnatally. The three fetuses without CHDs were delivered vaginally and have survived to date for 6, 8 and 15 years. CONCLUSIONS: Fetal bradycardia with 1 : 1 atrioventricular conduction caused by sustained sinus bradycardia or wandering pacemaker is an important type of fetal arrhythmia. Further investigations with a larger number of cases are required to determine the risk factors for predicting the outcome of affected fetuses.

Enlarged bronchial arteries in a fetus with transposition of the great arteries and intact ventricular septum.

Enlarged bronchial arteries are associated in some patients with transposition of the great arteries and intact ventricular septum. The etiology of these enlarged bronchial arteries is not yet known. In this report, we describe a case of TGA/IVS in which enlarged bronchial arteries were demonstrated from the prenatal period. The arteriogram at one year after arterial switch repair demonstrated enlarged bronchial arteries. This prenatal information may be useful for deciding on a strategy for postnatal treatment and counseling the family members.

Increased angiogenic growth factor in cyanotic congenital heart disease.

To examine the relationship between the plasma levels of angiogenic growth factors and the severity of cyanosis, 80 patients with cyanotic heart disease (CHD) and 81 healthy controls were studied. Median age and mean arterial blood oxygen saturation respectively were 4.2 years and 81% in CHD subjects and 4.8 years and 98% in controls. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were measured in plasma using enzyme-linked immunoassay. Plasma VEGF levels in controls depended negatively on age (p < 0.0001) until 3 months, when VEGF was no longer elevated. No such age dependence was found for HGF. Although VEGF levels did not differ between CHD and control subjects up to the age of 3 months, VEGF was significantly elevated in CHD patients older than 3 months compared to controls of similar age (149 +/- 106 vs 65 +/- 23 pg/ml, p < 0.0001). Moreover, the VEGF levels were negatively correlated with oxygen saturation (p = 0.03) and positively correlated with hemoglobin (p = 0.004) in CHD patients aged between 3 months and 10 years. Although the physiologic elevation of VEGF in the neonatal period decreases rapidly if oxygen saturation is normal, VEGF elevations persist if systemic hypoxia is present.

Soluble forms of the selectin family in children with Kawasaki disease: prediction for coronary artery lesions.

AIM: To investigate the relationship between the plasma levels of soluble forms of the selectin family and the incidence of coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: Thirty-three patients with KD, including group A patients (n = 22) who had no CALs and group B patients (n = 11) who had CALs, as well as age-matched febrile (n = 10) and afebrile controls (n = 11), were studied. RESULTS: Peak plasma E-selectin levels (172.0 +/- 58.6 ng ml(-1)) occurred during the acute phase of KD, while peak plasma P-selectin levels (260.3 +/- 43.2 ng ml(-1)) occurred during the subacute phase of the illness (p<0.05). Plasma L-selectin levels (1757.3 +/- 244.3 ng ml(-1)) during the convalescent phase tended to be higher than in either the acute or the subacute phase (not significant). Before intravenous immunoglobulin treatment, the plasma levels of E- (225.1 +/- 46.8 ng ml(-1)) and P-selectin (259.4 +/- 76.2 ng ml(-1)) of patients with CALs (n = 11) were significantly higher than those of patients (n = 22) with no CALs (E-selectin, 131.6 +/- 36.9 ng ml(-1); P-selectin, 184.9 +/- 84.6 ng ml(-1); p < 0.05). When a plasma E-selectin value before immunoglobulin treatment of >184.7 ng ml(-1) was used as the cut-off point, the sensitivity and specificity for the incidence of CALs were 81.8% and 90.9%, respectively. These findings demonstrate the relationship between plasma levels of selectins and disease severity of Kawasaki vasculitis. CONCLUSION: Higher plasma levels of E-selectin may have potential as a predictor of the incidence of coronary artery lesions in Kawasaki disease patients.

Assessment of the ability of myocardial contrast echocardiography with harmonic power Doppler imaging to identify perfusion abnormalities in patients with Kawasaki disease at rest and during dipyridamole stress.

The aim of our study was to assess the ability of myocardial contrast echocardiography (MCE) with harmonic power Doppler imaging (HPDI) to identify perfusion abnormalities in patients with Kawasaki disease at rest and during pharmacological stress imaging with dipyridamole. Results were compared with those of 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) imaging as the clinical reference standard. MCE with HPDI was performed on 20 patients with a history of Kawasaki disease. Images were obtained at baseline and during dipyridamole infusion (0.56 mg x kg(-1)) in the apical two- and four-chamber views. Myocardial opacification suitable for the analysis was obtained in all patients. Nine patients with stenotic lesions had a reversible defect after dipyridamole infusion detected by both MCE with HPDI and SPECT, and 3 patients with a history of myocardial infarction had a partially or completely irreversible defect detected by both methods. Three patients with coronary aneurysm without stenotic lesion, 4 patients with regressed coronary aneurysm, and 2 patients with normal coronary artery in acute phase also had normal perfusion at rest and after pharmacological stress by both methods. A 96% concordance (kappa = 0.87) was obtained when comparing the respective segmental perfusion scores using the two methods at baseline, and an 86% concordance (kappa = 0.81) was obtained at postdipyridamole infusion. After combining baseline and postdipyridamole images, each segment was labeled as having normal perfusion, irreversible defects, or reversible defects. Using these classifications, concordance for the two methods was 92% (kappa = 0.87). MCE with HPDI is a safe and feasible method by which to detect asymptomatic ischemia due to severe stenotic lesion, and it may be an important addition to the modalities used to identify patients at risk for myocardial infarction as a complication of Kawasaki disease.

Angiogenic growth factors in patients with cyanotic congenital heart disease and in normal children.

Previous studies have demonstrated that the expression of angiogenic growth factors is induced in hypoxic models. However, little is known about these factors in patients with cyanotic heart disease. The purpose of this study was to examine the relationship between the plasma level of angiogenic growth factors and the severity of cyanosis. The study included 85 patients with cyanotic heart disease and age matched 81 controls. Median age was 4.2 years in the cyanotic group and 4.8 years in the control group. Mean systemic oxygen saturation was 80.6 +/- 7.3% in the cyanotic group and 98.1 +/- 0.5% in the control group. In the control group, vascular endothelial growth factor (VEGF) in the neonatal period was significantly elevated, then rapidly decreased within 3 months after birth. After 3 months of age, VEGF levels remained at a plateau. In contrast, this age dependency did not occur in hepatocyte growth factor (HGF) levels. Although VEGF and HGF levels were not different between the cyanotic and control groups within 3 months after birth, the VEGF level in the cyanotic group after 3 months of age was significantly elevated compared to the levels measured in the control group (149.2 +/- 105.6 vs. 66.3 +/- 22.5 pg/ml, p < 0.0001). Moreover, the VEGF level was negatively correlated with oxygen saturation (y = 440.6-3.53x, R = 0.47, p < 0.0001) in cases more than 3 months old. In contrast, no correlation was found between HGF level and oxygen saturation. Although physiologically increased VEGF in the neonatal period was rapidly decreased under normal oxygen saturation, a higher VEGF level persisted if systemic hypoxia was present. Persistently higher VEGF level may be related to the development of systemic to pulmonary collateral arteries in patients with cyanotic heart disease.

Torn-off balloon tip of Z-5 atrial septostomy catheter.

Creation of atrial communication was performed in a newborn with critical aortic stenosis. After the success of the initial creation, balloon atrial septostomy using Z-5 catheter was performed. When catheter was pulled back, the tip of the balloon was torn off. This experience could be considered as noteworthy when using this catheter in patients with unusually thick atrial septum.

Quantitative assessment of severity of ventricular septal defect by three-dimensional reconstruction of color Doppler-imaged vena contracta and flow convergence region.

BACKGROUND: The aim of the present study was to investigate the feasibility and potential value of the computer-controlled, 3D, echocardiographic reconstruction of the color Doppler-imaged vena contracta (CDVC) and the flow convergence (FC) region as a means of accurately and quantitatively estimating the severity of a ventricular septal defect (VSD). METHODS AND RESULTS: We performed a 3D reconstruction of the CDVC and the FC region in 19 patients with an isolated VSD using an ultrasound system interfaced with a Tomtec computer. The variable asymmetric geometry of the CDVC and the FC region could be 3D-visualized in all patients. The 3D-measured areas of CDVC correlated well with volumetric measurements of the severity of VSD (r=0.97, P:<0.001). Regression analysis between the shunt flow rate (calculated from the product of the area of CDVC and the continuous Doppler-derived velocity time integral) and the corresponding reference results (calculated by cardiac catheterization) demonstrated a close correlation (r=0.95, P:<0.001). There was also a good correlation between shunt flow rates calculated using the conventional 2D, 1-axis measurement of the FC isovelocity surface area with the hemispheric assumption (r=0.95, P:<0.001); shunt flow rates calculated using 3D, 3-axis measurements of the FC region (r=0.97, P:<0.01); and reference results by cardiac catheterization. However, the 2D method substantially underestimated the actual shunt flow rate. CONCLUSIONS: The 3D reconstruction of the CDVC and the FC region may aid in quantifying the severity of VSD.

Sequential evaluation of left ventricular myocardial performance in children after anthracycline therapy.

This study prospectively assessed subclinical cardiotoxicity in patients undergoing chemotherapy by using the Tei index combining systolic and diastolic time intervals. A significant difference in the Tei index was observed between patients who received a low dose and those who received a moderate to high dose of anthracycline antibiotic drugs. The Tei index is a sensitive, accurate, and easy approach for detecting subclinical anthracycline cardiotoxicity.

Quantitation of the global right ventricular function in children with normal heart and congenital heart disease: a right ventricular myocardial performance index.

Although the assessment of right ventricular (RV) function is important in the clinical management of children with congenital heart disease, available imaging techniques have been limited because of the complex geometry of the right ventricle. A new Doppler index combining systolic and diastolic time intervals (the Tei index) has been reported to be useful for the assessment of global RV function in adults. However, normal values in children, age-related changes, and the clinical utility of the Tei index with regard to congenital heart disease have not been demonstrated. The purpose of this study was to prospectively assess RV function in children with normal heart and congenital heart disease using the Tei index. The subjects included 150 healthy children and 43 patients with congenital heart disease (35 patients with atrial septal defects and 8 patients who had had a Senning operation). The index was defined as the sum of isovolumetric contraction time and isovolumetric relaxation time divided by ejection time and was measured from conventional RV outflow and inflow Doppler velocity profiles. The Tei index was not affected by age in healthy children (0.24 +/- 0.04). There was a significant difference in index rating between patients who had had a Senning operation (0.58 +/- 0.09) and healthy children (p < 0.01), but there was no significant difference between children with atrial septal defect (0.25 +/- 0.13) and healthy children. The Tei index is a feasible approach to use when assessing global RV function in children with congenital heart disease.

Progression of congenital heart disease in the prenatal period.

BACKGROUND: Prenatal echocardiography has shown evidence of prenatal development of congenital heart disease. Prenatal cardiac anatomy, chamber size and function change during gestation, so that the appearance of cardiac structure in abnormal hearts may be different from that which is usually seen postnatally. METHODS: Published prenatal echocardiographic studies were reviewed and in utero development of congenital heart disease from midtrimester to the early postnatal period is discussed. RESULTS: The growth of the great vessels and ventricles is reduced in fetuses with ventricular outflow obstruction. Valve regurgitation may progress. The foramen ovale and ductus arteriosus have been reported to become restrictive in utero in several settings. Pulmonary vascular obstructive changes may progress prenatally. Fetal arrhythmia (both bradycardia and tachycardia) may develop in utero. Development of congestive heart failure is a very important issue during follow up of fetuses with significant cardiac or extracardiac problems. Some may progress to fetal hydrops and prognosis of the affected fetuses is usually very poor. CONCLUSIONS: Correct knowledge of possible development is important for accurate prenatal diagnosis. Information on prenatal progression of the cardiac anomaly is also important to make plans for follow up and perinatal management, to predict outcomes and to counsel family. Furthermore, the benefits of prenatal treatment instead of postnatal treatment should be assessed by the accurate prediction of the progression of the cardiac problem in utero. Further extensive studies using a large number of cases is required to predict progression accurately. In addition, further studies for elucidating the mechanisms of progression is important to provide better outcomes for fetuses with various congenital heart diseases.