Early diagnosis and treatment of atrioventricular block in the fetus exposed to maternal anti-SSA/Ro-SSB/La antibodies: a prospective, observational, fetal kinetocardiogram-based study.

BACKGROUND: A fetus exposed to maternal anti-SSA/Ro or anti-SSB/La antibodies (or both) may develop complete atrioventricular block (AVB), which results in high prenatal and postnatal morbidity and mortality. Until recently, only high-grade AVB could be diagnosed in utero. The tissue velocity-based fetal kinetocardiogram (FKCG) enables accurate measurement of AV conduction time and diagnosis of low-grade AVB. In the present multicenter observational study, we used FKCG to detect first-degree AVB in fetuses at risk. METHODS AND RESULTS: FKCG was performed in 70 fetuses of 56 mothers who were positive for anti-SSA/Ro and/or anti-SSB/La. Fetuses were monitored with weekly FKCG from 13 to 24 weeks' gestation, followed by monthly assessments until delivery in unaffected fetuses and weekly assessments in affected fetuses. AV conduction in 70 at-risk and 109 normal fetuses was compared. FKCG was obtained readily in all fetuses; 6 showed first-degree AVB (AV conduction time >2 z scores above normal mean) at 21 to 34 gestational weeks. Immediate maternal treatment with dexamethasone resulted in normalization of AV conduction in all affected fetuses within 3 to 14 days. AV conduction time in the remaining 64 untreated fetuses remained normal throughout gestation. The ECG PR interval immediately after birth was normal in all affected newborns. No child developed AVB or cardiomyopathy in the subsequent 1- to 6-year (median 4-year) follow-up. CONCLUSIONS: The present findings suggest that an FKCG can detect first-degree AVB in the fetus exposed to maternal anti-SSA/Ro or anti-SSB/La antibodies (or both). Dexamethasone given on detection was associated with normalized AV conduction in fetuses with first-degree AVB. No fetus in the present study developed complete prenatal or postnatal AVB.

Tetralogy of Fallot with pulmonic atresia with cyclic occlusion of an associated aortic sinus of Valsalva-pulmonary artery window.

A first case of an unusual aortopulmonary window with tetralogy of Fallot associated with pulmonary atresia is presented. The aortopulmonary window was at the aortic sinus of Valsalva. The left aortic leaflet prevented pulmonary hypertension by occluding the window in systole.

NT-proBNP as a marker for persistent cardiac disease in children with history of dilated cardiomyopathy and myocarditis.

Children with myocarditis and dilated cardiomyopathy may recover clinically and echocardiographically. Plasma levels of the N-terminal segment of B-type natriuretic peptide prohormone (NT-proBNP), a sensitive marker for cardiac dysfunction, may reflect residual cardiac damage in these patients. The purpose of this study was to evaluate NT-proBNP status in pediatric patients with a history of myocarditis and dilated cardiomyopathy. Cardiac evaluation was performed and the levels of NT-proBNP were measured in 23 children who had a history of myocarditis or dilated cardiomyopathy. NT-proBNP levels were also measured in 56 age-matched control children. Nine of the 23 patients had evidence of left ventricular dysfunction (DCM group), whereas 14 had none (recovery). NT-proBNP levels were higher in the DCM group (3154 +/- 2858 pg/ml) than in the recovery group (122 +/- 75 pg/ml, p < 0.001) and the control group (113 +/- 96 pg/ml, p < 0.001). There was no difference between the recovery and the control groups (p = 0.45), and none of the recovered patients had a NT-proBNP level higher than the upper limit of normal. The area under the receiver operating characteristics curve for the diagnosis of persistent left ventricular dysfunction was 0.984. NT-proBNP levels correlated with echocardiographically derived shortening fraction and with clinical score. NT-proBNP is a good marker for persistent left ventricular dysfunction in children who have had myocarditis or cardiomyopathy. In this group of patients, NT-proBNP levels are normal in children who recover echocardiographically, suggesting no residual hemodynamic abnormalities.

N-terminal pro-B-type natriuretic peptide: reference plasma levels from birth to adolescence. Elevated levels at birth and in infants and children with heart diseases.

AIM: Determination of plasma levels of N-terminal pro-B-type natriuretic peptide (N-BNP) in infants and children with and without heart diseases. METHODS: Plasma N-BNP was measured in 78 infants and children without heart disease and in 55 infants and children with heart disease causing volume and pressure overload. Heart diseases included chronic dilated cardiomyopathy, acute left ventricular dysfunction, and congenital cardiac anomalies resulting in left and right ventricular volume or pressure overload. The Mann-Whitney rank-sum test and the ANOVA for ranks test were used to compare two or more groups, respectively. RESULTS: N-BNP levels were elevated in the first days of life but were not significantly different in children from 4 mo to 15 y old. The upper limit in children older than 4 mo with no heart disease was 349 pg/ml. In patients with heart disease, N-BNP levels were significantly higher than in control children (p < 0.0001). CONCLUSION: N-BNP levels are elevated in the first days of life and are stable from age 4 mo to adolescence. Elevated N-BNP levels reflect cardiac dysfunction in infants and children.

Use of tissue velocity imaging in the diagnosis of fetal cardiac arrhythmias.

BACKGROUND: Precise diagnosis of cardiac arrhythmias in the fetus is crucial for a managed therapeutic approach. However, many technical, positional, and gestational age-related limitations may render conventional methods, such as M-mode and Doppler flow methodologies, or newer techniques, such as fetal electrocardiography or magnetocardiography, difficult to apply, or these techniques may be unsuitable for the diagnosis of fetal arrhythmias. METHODS AND RESULTS: In this prospective study, we describe a novel method based on raw scan-line tissue velocity data acquisition and analysis. The raw data are available from high-frame-rate 2D tissue velocity images and allow simultaneous sampling of right and left atrial and ventricular wall velocities to yield precise temporal analysis of atrial and ventricular events. Using this timing data, a ladder diagram-like "fetal kinetocardiogram" was developed to diagram and diagnose arrhythmias and to provide true intervals. This technique was feasible and fast, yielding diagnostic results in all 31 fetuses from 18 to 38 weeks of gestation. Analysis of various supraventricular and ventricular arrhythmias was readily obtained, including arrhythmias that conventional methods fail to diagnose. CONCLUSIONS: The fetal kinetocardiogram opens a new window to aid in the diagnosis and understanding of fetal arrhythmias, and it provides a tool for studying the action of antiarrhythmic drugs and their effects on electrophysiological conduction in the fetal heart.

Association between increased central venous pressure and hydrocephalus in children undergoing cardiac catheterization. A prospective study.

OBJECTS: The relationship between increased central venous pressure (CVP) and development of hydrocephalus has been extensively discussed in the neuropediatric literature. However, the possibility of a direct connection has not been systematically examined. The purpose of this prospective study was to examine whether there was a correlation between elevated CVP and hydrocephalus in children undergoing cardiac catheterization. METHODS: We used cardiac catheterization to measure the right atrial and superior vena caval pressure in 37 children (mean age 30 months) with congenital heart malformations. The children had CVP higher than normal (mean 10.2+/-3.1 mmHg, range 4-18). To evaluate the size of the lateral and fourth ventricles, we performed CT scans of the brain on each child. Abnormal scans were found in 15/37 children, showing brain atrophy (12/37), ventriculomegaly (3/37), and focal infarction (1/37). Cerebral atrophy was more likely to occur in young children (P<0.001). The average head circumference among these children was less than 2SD below the mean for healthy children of comparable ages. Using a correlation coefficient regression model, no relationship was found between CVP and ventricular diameters or head circumference. CONCLUSIONS: These results argue against the hypothesis that mild to moderately elevated venous pressure is involved in the mechanism and development of pediatric hydrocephalus.

Use of high-frame rate imaging and doppler tissue echocardiography in the diagnosis of fetal ventricular tachycardia.

Ventricular tachycardia has rarely been diagnosed in the fetus. We describe a 31-week-old fetus with ventricular tachycardia and severely depressed ventricular function. M-mode and 2-dimensional Doppler tissue echocardiography were used in this study to assess the nature of the arrhythmia. The complete atrioventricular dissociation inherent to the diagnosis of ventricular tachycardia was particularly easy to detect with M-mode Doppler tissue echocardiography. Moreover, the onset and the pattern of propagation of the ventricular arrhythmia could be easily identified with 2-dimensional Doppler tissue echocardiography. Doppler tissue echocardiography facilitates the diagnosis of ventricular tachycardia and adds new information that is not available by other techniques.

Propofol does not modify the hemodynamic status of children with intracardiac shunts undergoing cardiac catheterization.

Immobility and cardiovascular stability are required for cardiac catheterization. Pediatric patients need a type of sedation that also allows spontaneous ventilation without supplemental oxygen. Propofol has been adequate in hemodynamically stable patients with congenital heart disease undergoing cardiac catheterization. However, mild systemic hypotension caused by propofol may increase a preexisting right-to-left shunt. The aim of this study is to evaluate, in pediatric patients scheduled for cardiac catheterization, the effects of propofol on systemic and pulmonic circulations. Fifteen patients aged 18 months to 9 years were studied. After a fast of 4-6 hours for solid food, the patient arrived at the cardiac catheterization suite, where an IV catheter was placed. Usual monitoring was used. For sedation, without supplemental oxygen, patients received 1 mg/kg of fentanyl followed by propofol (1-2 mg/kg) titrated to immobility during preparation of the groin. A continuous infusion of propofol (100 mg/kg/min) was also started to obtain immobility during the procedure. Hemodynamic data, including systemic venous, pulmonary artery and vein, aortic saturations, and pressures, were recorded; Qp and Qs were calculated. The same set of data was re-corded 4 minutes after discontinuation of propofol and when the patient was responding to tactile stimuli. Despite lower pressures during propofol infusion, as compared with those pressures measured after discontinuation of propofol, the extent of the intracardiac shunt remained unchanged. Propofol seems to be an adequate sedative agent for pediatric patients undergoing cardiac catheterization, including those with intracardiac shunts.

Rhabdomyoma in the fetus: illustration of tumor growth during the second half of gestation.

Rhabdomyomata are the most common cardiac tumors in childhood and are associated with tuberous sclerosis. These tumors tend to regress in the first years of life. Little is known about their intrauterine growth pattern. We describe three fetuses with cardiac rhabdomyomata and illustrate the tumor growth by serial echocardiographic views during the second half of gestation. Tumor growth is proportional to cardiac growth and tends to be somewhat slower toward the end of pregnancy.

The coronary sinus in the fetus.

INTRODUCTION: The normal coronary sinus drains venous blood from the cardiac veins to the right atrium. In some instances, the coronary sinus may be dilated due to volume or more rarely pressure overload. AIMS: To assess the feasibility of detecting the coronary sinus in the fetus and to establish the normal values of the coronary sinus dimensions throughout gestation. SUBJECTS AND METHODS: Fetal echocardiography was performed in 78 normal fetuses from the 16th to the 40th week of gestation (median 25 week). The coronary sinus was measured in four-chamber view (87% of cases) or in parasternal short axis view equivalent (13%). A second group of nine fetuses with a dilated coronary sinus was compared to the normal group. RESULTS: Adequate imaging of coronary sinus was obtained in 97.4% of the normal fetuses. The diameter of the coronary sinus ranged from 1 to 3.2 mm (2 mm +/- 0.13 mm, mean +/- 5% confidence interval) and correlated well with the age of pregnancy (r = 0.86). The length-to-diameter ratio of 24% (+/- 6%) did not vary throughout pregnancy. All nine fetuses with a dilated coronary sinus had a persistent left superior vena cava which drained into it. The diameter of the coronary sinus was approximately three times larger in the abnormal group with a diameter-to-length ratio of approximately 83% (P < 0.0001). CONCLUSION: The coronary sinus is readily identified in the fetus. It gradually increases during pregnancy. An abnormal coronary sinus is easily diagnosed and should prompt the sonographer to look for a persistent left superior vena cava.

Significance of a cardiac murmur as the sole clinical sign in the newborn.

A cardiac murmur is a very common finding in the first few days of life. It is traditionally believed that lesions creating left-to-right shunts do not present so early. This study was aimed to define and to classify the causes of a murmur in a newborn with an otherwise normal examination. All echocardiograms performed on newborns aged 1-5 days who were referred for evaluation of a murmur in a 3-year period were reviewed. Newborns with additional clinical signs or antenatal diagnosis of a cardiac disease were excluded. Of 20,323 live births, there were 170 newborns referred for echocardiogram solely because of a murmur. Of these, 147 (86%) were found to have structural heart defects. The most common lesions found were those creating left-to-right shunts (66%). Ventricular septal defect was the most common single lesion (54/147, 37%), followed by patent ductus arteriosus (34 newborns, 23%). The combination of both was found in 10 newborns (7%). Six newborns (4%) had pulmonary valve stenosis and three (2%) aortic valve stenosis. Seven newborns (5%) had unforeseen complex heart disease. For five of them, delayed diagnosis would have resulted in potentially life-threatening conditions. There was no correlation between the category of lesion and the age of presentation. The audible threshold of a murmur correlated with a maximum instantaneous gradient of 25 mm Hg (range 11-46 mm Hg). Thirteen percent of newborns with isolated heart murmur had no identifiable structural heart disease. These data suggest that most asymptomatic newborns presenting with a murmur in the first days of life have structural heart disease. Some of the more serious defects would not have been diagnosed without early echocardiography. A left-to-right shunt, particularly a ventricular septal defect, may cause a murmur even the first day of life and is probably more common that has been acknowledged.

Giant congenital aortic aneurysm with cleft sternum, supraumbilical raphé, and hemangiomatosis: report and review.

We report on a child with giant congenital aortic aneurysm, sternal defect, hemangiomas of face, supraumbilical raphé, and review the only two other cases reported to date. Congenital aortic aneurysm is an ominous malformation that has to be systematically searched in children with the sternal malformation/vascular dysplasia complex.

Antenatal diagnosis of cardiac malformation: a structural study.

The purpose of this study was to find out the functional and anatomical relationship between the various cardiac segments in congenital heart disease before and after birth. This study of cardiac pathology focused on 227 fetuses referred to fetal echocardiography because of suspicion of congenital heart defects (CHD) from 1986 to 1991. The heart was imaged and classified according to a division into 7 adjacent segments. Normality or abnormality of each segment and of the general state of the subject's heart was coded in a binary mode, in which 0 = normal and 1 = pathological. We also coded the extracardiac morphology, noting existence or absence of another extracardiac defect in the fetus. The binary segmental data were entered into a worksheet for further analysis. Observations were conducted prenatally and verified after birth or abortion. Fetal echocardiography was first assessed using conventional statistical analysis. The calculated accuracy and predictive values to diagnose any cardiac defect as well as for correctly coding abnormal or normal cardiac segments were excellent. Then, using HUDAP software (Hebrew University Data Analysis Package), we could demonstrate a perfect fit between the functional and pathological structure of the cardiac segments in the fetus. Moreover, using this unique type of data analysis, we found a multidimensional scaling confirmation of the embryogenesis theory of the heart.

In situ FTIR reaction analysis of pharmaceutical-related chemistry and processes.

The potential for the production of increasing numbers of drug candidates as a result of combinatorial techniques, coupled with the necessity of striving for safer, more efficient processes, poses a special challenge and opportunity to the development chemist and engineer. In support of this quest for better molecules and processes, in situ analytical methodologies are becoming an ever-important ally. In particular, in situ FTIR spectroscopy is providing a wealth of information about reaction kinetics, pathways and mechanisms for a wide range of chemistry in both academic and industrial laboratories. This review article provides an historic perspective on the use of in situ FTIR spectroscopy and covers the recent literature published as a variety of pharmaceutical-related topics.

Noninvasive external pacing in the newborn.

Complete atrioventricular block in the newborn occasionally requires emergency intervention when the heart rate is too low to provide adequate cardiac output. While medications are frequently ineffective, emergent implantation of a pacemaker is not always feasible and carries a significant morbidity. We report two cases of complete atrioventricular block in newborns treated immediately after birth with an external noninvasive pacemaker system.

Agenesis of tibia with ectrodactyly/Gollop-Wolfgang complex associated with congenital heart malformations and additional skeletal abnormalities.

We report on a child with bifid femur, absent tibiae, hypoplastic hallux, bilateral club feet, congenital heart defects, and segmentation anomalies of the spine and ribs. Parents are consanguineous, from a region where other consanguineous families with similarly affected individuals have been reported. Clinical and genetic controversies of the tibial aplasia-ectrodactyly syndrome/Gollop-Wolfgang complex are discussed.

Contraction of the fetal ductus arteriosus induced by diclofenac. Case report.

The ductus arteriosus in the fetus may contract after administration of nonsteroidal anti-inflammatory drugs such as indomethacin and aspirin. We report a similar effect observed after a 36-week pregnant women was given diclofenac against flank pains. The ductus of this fetus was vasoconstricted with evidence of right ventricular hypertension. It resolved after cessation of the drug. Diclofenac is a cyclo-oxygenase inhibitor and thus carries the pharmacodynamic properties of other nonsteroidal anti-inflammatory drugs with inhibition of prostaglandin synthesis, resulting in vasoconstriction of the ductus arteriosus. We suggest monitoring of the fetal ductus state and velocities by fetal echocardiography in women treated with diclofenac.

Detection of an obstructive membrane in the ductus arteriosus of a fetus using high frame rate echocardiography.

We examined a fetus at 38 weeks of gestation because of marked disproportion in size of the left and right ventricles. A membrane was detected at the distal end of the ductus arteriosus with significant flow gradient through it. New echocardiographic technologies such as high frame rate imaging and dynamic beam focusing increase spatial and temporal resolution and enhance more precise anatomical diagnosis in the fetus. This ductal membrane might have been related to the transient tachypnea from which the baby suffered after birth.