Amiram Nir

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.

Amino-Terminal Pro-Brain-Type Natriuretic Peptide: Heart or Lung Disease in Pediatric Respiratory Distress?

Objectives. The aim of this study was to determine whether plasma levels of amino-terminal pro-brain natriuretic peptide (N-BNP) could differentiate between heart failure and lung disease among infants with acute respiratory distress. In addition, our aim was to determine whether plasma levels of N-BNP could be used to monitor the effects of treatment among infants with heart failure. Methods. Infants (age range: 1–36 months; median age: 10 months) who presented with respiratory distress underwent physical examination, plasma N-BNP measurement, and echocardiography within 24 hours after admission. Seventeen infants were finally diagnosed with acute heart failure and 18 with acute lung disease. Thirteen healthy infants served as a control group. Results. Plasma N-BNP levels were significantly higher for the infants with heart failure (median: 18452 pg/mL; range: 5375–99700 pg/mL) than for the infants with lung disease (median: 311 pg/mL; range: 76–1341 pg/mL). Among the infants with heart failure, there was a significant difference in plasma N-BNP levels before and after congestive heart failure treatment. Conclusion. Among infants with respiratory distress, plasma N-BNP measurements can differentiate between acute heart failure and lung disease and can be used to monitor the effects of treatment for infants with heart failure.

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.

N-terminal-proB-type natriuretic peptide as a marker for acute anthracycline cardiotoxicity in children.

Background Anthracyclines are widely used in the treatment of pediatric cancer but their use is associated with cardiotoxicity. The cardiotoxic effect may become clinically apparent many years after therapy, and no reliable method exists for early detection of cardiac damage while the patient is receiving the drug. The natriuretic peptides have been established as markers for anthracycline-induced cardiotoxicity in adults and markers for cardiac dysfunction in children. We examined whether N-terminal proB-type natriuretic peptide (NT-proBNP) may be used as a marker for anthracycline-induced cardiotoxicity in children. Methods Twenty-three consecutive pediatric patients with newly diagnosed cancer were enrolled in this study. All patients received anthracycline-containing chemotherapy. Fifty-four age-matched children served as controls. Serial measurements of plasma NT-proBNP levels were taken before and after each anthracycline-containing course. Echocardiograms were performed before initiation of treatment and at the end of the study. Results Plasma levels of NT-proBNP were within normal limits before treatment and increased significantly only after the first anthracycline dose (from 150±112 to 327±321 pg/mL, mean±SD, P=0.02) and not after subsequent doses. This increase was attributed mainly to a subgroup of patients who received more than 25 mg/m2 of doxorubicin. In 14 patients (61%), the highest NT-proBNP level occurred after the first anthracycline dose. All patients had normal echocardiograms and none developed heart failure. Conclusions NT-proBNP increases significantly after the first anthracycline course in a subset of pediatric cancer patients. This increase is not associated with clinical or echocardiographic evidence of cardiac dysfunction. Anthracyclines may be more cardiotoxic in the first course than in subsequent courses. Longer follow-up of these patients is necessary to determine whether NT-proBNP can be used as an early marker for anthracycline-induced cardiotoxicity.

Risk Factors for Cardiovascular Disease in Children and Young Adults after Renal Transplantation

Despite good outcomes in pediatric renal transplantation, life expectancy is reduced, mostly as a result of accelerated atherosclerosis. A comprehensive evaluation of cardiac status and risk factors for cardiovascular disease was performed in 60 patients after renal transplantation (age 3 to 29 yr; mean 15.8). Posttransplantation diabetes was diagnosed in 7%. Half of the patients did not engage in any physical activity, and this was associated with increased body mass index. Uncontrolled hypertension was found in 13% of patient, and 53% were on antihypertensive medications. BP index was associated with left ventricular mass index (LVMI). Dyslipidemia was relatively uncommon, with hypercholesterolemia found in 15% and elevated LDL cholesterol found in 10% of patients. Hyperhomocysteinemia was frequent (58%); in most patients, it was not due to folate or B(12) deficiency. Lipid and homocysteine abnormalities were associated with cyclosporine therapy. Echocardiography demonstrated normal LVMI in 93% of patients, although LVMI was higher than in healthy control subjects. Cardiac troponin I was normal in all patients, but N-terminal pro-brain natriuretic peptide was elevated in 35% and was associated with LVMI and renal function. Although present cardiac status is relatively normal in pediatric renal transplantation patients, cardiac risk factors are common, and strategies to prevent cardiovascular disease need to be developed.

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.

A comprehensive study of cardiovascular risk factors, cardiac function and vascular disease in children with chronic renal failure

BACKGROUND Cardiovascular disease causes major morbidity and is an important determinant of premature death in the paediatric chronic kidney disease (CKD) population. It is composed of three separate, although interrelated, disease processes: atherosclerosis, arteriosclerosis (i.e. medial vascular calcifications) and myocardial disease. Myocardial consequences of atherosclerosis barely exist in children, thus providing a good opportunity to investigate the role that kidney disease plays in the development of cardiovascular disease. METHODS We assessed 70 patients, aged 4 months to 18 years, with chronic kidney disease stages 3-5, for known risk factors of cardiovascular disease and for additional laboratory and clinical variables which may have an impact on this disease process. Carotid artery ultrasound was used to evaluate vascular structure and function, whereas myocardial disease was assessed by echocardiography. RESULTS Traditional risk factors, although present in this cohort, did not accumulate with progression of chronic kidney disease. Non-traditional risk factors increased in number and severity in correlation with the stage of CKD. The main myocardial abnormalities were left ventricular hypertrophy and diastolic dysfunction. Vascular function tests correlated with calcium-phosphate metabolism variables, homocysteine and time-averaged serum uric acid. CONCLUSIONS This study shows that children with CKD are exposed to risk factors and demonstrate signs of cardiovascular disease already at a young age. The possible role of uric acid and homocysteine in the evolution of cardiovascular disease is discussed. Further studies looking at possible interventions to prevent cardiovascular morbidity and mortality in this high risk population are needed.

Ibuprofen Versus Continuous Indomethacin in Premature Neonates With Patent Ductus Arteriosus: Is the Difference in the Mode of Administration?

Ibuprofen has been proposed as a preferential alternative to indomethacin in treating patent ductus arteriosus (PDA), because it is purported to have less renal, mesenteric, and cerebral vasoconstrictive effects. However, short and long-term safety concerns regarding ibuprofen remain. Continuous slow infusion of indomethacin also eliminates peripheral vasoconstriction and may thus offer similar benefits to ibuprofen without safety concerns. In this study, our objective was to show that treating a PDA with continuous indomethacin is similar to ibuprofen in its effect on urine output, renal function, and blood flow velocities in the renal, superior mesenteric, and anterior cerebral arteries. Sixty four prematures with PDA were randomly, prospectively assigned to either treatment. PDA closure rates were similar (74 versus 59%; p = 0.123). Nine indomethacin-treated babies (29%) versus twelve ibuprofen babies (38%) underwent repeated therapy (p = 0.656). Two indomethacin and four ibuprofen infants required surgical ligation (p = 0.672). Serum creatinine, oliguria, estimated glomerular filtration rate, and fractional excretion of sodium were similar in both groups, as were blood flow velocity parameters in the vessels studied. There were no differences in necrotizing enterocolitis, BPD, intraventricular hemorrhage, and/or retinopathy of prematurity. In conclusion, PDA treatment with either continuous indomethacin infusion or ibuprofen was equally devoid of adverse renal effects and/or peripheral vasoconstrictive effects.

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.

Value of amino-terminal pro B-natriuretic peptide in diagnosing Kawasaki disease

Background:  The aim of the present study was to investigate the diagnostic value of the N‐terminal B‐type natriuretic peptide (NT‐proBNP) in acute Kawasaki disease (KD) given that the clinical criteria and the current basic laboratory tests lack the necessary specificity for accurate diagnosis.