Low-density lipoprotein apheresis in a patient aged 3.5 years.

UNLABELLED: A 3.5 y-old girl carrying a severe mutation of the LDL-receptor gene known as "FH Pavia", affected by homozygous familial hypercholesterolaemia (FH), and at high risk of developing coronary artery atherosclerosis was treated with selective dextran sulphate cellulose (DSC) column low-density lipoprotein apheresis (LDL-a). This is the youngest patient ever treated with LDL-a. Plasma total cholesterol (982 mg/dl) and LDL-cholesterol (939 mg/dl) (T-Chol, LDL-Chol) levels at baseline showed a transient decrease: -13.4%, and -16.8%, respectively, after 9 mo of combined treatment with a diet, cholestyramine (max. 12 g/d) and atorvastatin (max. 30 mg/d). However, the drugs were discontinued because of intolerance and an increase in aminotransferases and creatine phosphokinase in the plasma. Moreover, after 9 mo of this therapy, the mean plasma T-Chol and LDL-Chol levels were still high (930 mg/dl and 869.5 mg/dl, respectively). Therefore, 9 consecutive treatments with LDL-a were carried out every 15 d (plasma volumes treated: 1000-1700 ml). Mean plasma T-Chol, LDL-Chol, triglycerides (TG), and Lp(a) decreased significantly: -75.5%, -77.2%, -67.5% and -50.8%, respectively. HDL-cholesterol (HDL-Chol) concentration was considerably decreased immediately after apheresis because of haemodilution (X: -45.1%). CONCLUSION: LDL-a treatment improved the plasma apo B 100-containing lipoproteins--LDL, Lp(a)--profile in a homozygote with a severe inherited disorder in which coronary artery atherosclerosis frequently has its clinical onset before 10 y of age. At the time of this report, no significant side effects had been observed.

Human parvovirus B19 infection in infancy associated with acute and chronic lymphocytic myocarditis and high cytokine levels: report of 3 cases and review.

Human parvovirus B19 infection is occasionally associated with acute lymphocytic myocarditis (ALM). Three infants with B19 virus-associated ALM were followed up clinically, histologically, and immunovirologically. Each infant had B19 virus DNA in the blood or B19 virus-specific IgM antibodies. Two infants with postnatal infection recovered after immunosuppressive therapy. The third infant with possible prenatal infection developed chronic persistent myocarditis associated with persistent B19 virus DNA in the blood. All 3 infants had increased levels of interferon-gamma, tumor necrosis factor-alpha, and interleukins -6 and -8. Four newborns with congenital B19 virus infection and 4 infants and children who had postnatally acquired B19 virus infection without myocarditis all had normal levels of these cytokines. These observations suggest that B19 virus infection in infancy causes ALM in some infants and children.

Peculiarities of prevalence and morphology of congenital heart disease detected in utero.

Intrauterine echocardiography is changing our knowledge of congenital heart disease; cardiac defects diagnosed in utero have distinctive features of both prevalence and morphology when compared with those observed just after birth. We reviewed a series of 171 fetal heart conditions: 148 were diagnosed at intrauterine echocardiography, the diagnosis being verified at autopsy in 41, and 23 were observed at the postmortem only. Peculiarities of prevalence consisted in an excess of various defects, such as hypoplastic left heart syndrome, atrial isomerism, pulmonary atresia, and atrioventricular and atrial septal defects, and in a reduced number of completely different conditions, such as transposition of great arteries and aortic coarctation. Differences in prevalence have been attributed to difficulties in diagnosing some particular anomalies in utero, to the selection of pregnancies undergoing screening, and to the special intrauterine evidence of some heart defects. Peculiarities in morphology result from the coexistence with extracardiac malformations, from the changes in shape conditioned by fetal hemodynamics, and from the intrauterine evolution of the morphology of some malformations. We concluded that the knowledge of these characteristic traits was helpful to cardiac pathologists, pediatric cardiologists, and obstetricians, and allowed the re-evaluation of the role of hemodynamic factors in remodeling the malformed cardiovascular appara-tus.

LDL apheresis in a homozygous familial hypercholesterolemic child aged 4.5.

Preliminary experience with the efficacy and safety of dextran sulfate cellulose low-density lipoprotein (LDL) apheresis for the treatment of a 4.5-year-old girl with homozygous familial hypercholesterolemia and coronary artery disease is reported. The decrease of the most atherogenic apolipoprotein B-containing lipoproteins, low-density lipoprotein (LDL) and lipoprotein(a) (Lp [a]), were in the ranges of 63.1-68.7%, and 52.5-58.6%, respectively. The child tolerated LDL apheresis without any clinically significant complications. Therefore, she was submitted to a long-term program of treatment at intervals of 15 days. The experience suggests the possibility of an early beginning of extracorporeal treatment with LDL apheresis in children severely affected by homozygous or double heterozygous familial hypercholesterolemia.

Use of ICRF-187 for prevention of anthracycline cardiotoxicity in children: preliminary results.

The objective of this study is to assess the efficacy of ICRF-187 as a protective agent against anthracycline cardiotoxicity. Cardiac function was evaluated by echocardiography before and after each cycle of anthracycline chemotherapy associated with ICRF-187 and compared with that of a second group receiving anthracycline chemotherapy without ICRF-187. The patients were a group of 15 consecutive children affected with various types of solid tumors who were treated with either doxorubicin-daunomycin or epirubicin (average doses 340 and 280 mg/m2, respectively), and treatment was associated with ICRF-187. A second group of 15 consecutive children affected with different malignancies were simultaneously treated with either doxorubicin-daunomycin or epirubicin (average doses 309 and 270 mg/m2, respectively), but without ICRF-187 association. None of the patients treated with anthracyclines and ICRF-187 association showed abnormalities on echocardiographic examination. In the second group of patients treated with anthracyclines but without ICRF-187 association, we observed a decrease in the left ventricular ejection fraction to < 55% and a decrease in the left ventricular fractional shortening to < 28% in two patients (13.3%). One of these (6.6%) showed a dilatative cardiomyopathy. Both groups of patients were treated with low doses of anthracyclines. Although this study was not randomized, in patients without ICRF-87 cardioprotection, there was a trend for a worse evolution with one case of clinical cardiomyopathy as well as subclinical cardiac abnormalities.

[Prevalence of congenital cardiopathies among newborn infants in a department of pediatric cardiology]. / Prevalenza delle cardiopatie congenite in età neonatale in un reparto di cardiologia pediatrica.

This study consists of a prevalence congenital heart disease (CHD) registered in the Pediatric Cardiology Department of Umberto I General Hospital in Rome between January 1st 1992 and December 31-th 1993. Cases recorded in this period have been taken part of a larger study called Italian Multicentric Study for recording and follow-up of congenital heart disease (IMS-CHD); the purpose is to determine the prevalence of CHD in Italy and discover the outcome of affected children. In this duration, 187 new cases have been recorded, in which 63.6% had a single defect while 36.4% had multiple defects. These isolated defects were most frequently occurred (51.9%) following the stenosis of the pulmonary artery (15.5% and the defects of the interatrial septum (15%).

Permanent mechanical catheter ablation of an accessory pathway in a child.

Permanent mechanical ablation of an accessory atrioventricular pathway was observed in an infant during intracavitary electrophysiological mapping. The persistent lack of preexcitation was confirmed during a 15-month follow-up period.

[Anatomo-clinical correlations of cardiopathies diagnosed during fetal life: analysis of 110 cases of cardiopathies]. / Correlazioni anatomo-cliniche delle cardiopatie diagnosticate durante la vita fetale: analisi di una casistica di 110 cardiopatie.

BACKGROUND: Fetal echocardiography has achieved high sensibility and specificity rates and it has become a reliable tool to detect intra-uterine congenital heart defects. OBJECTIVES: The purpose of the present study was to clarify the potential of anatomo-clinical correlation in fetal echocardiography not only for diagnosing heart defects, but also for understanding and following their morphogenesis and natural history in utero. METHODS: Nine hundred pregnancies, referred by several first-level centers, have been followed up from the sixteenth week to birth, and the newborn baby has been studied, too. In case of either voluntary abortion, or intra-uterine or neonatal death, a post-mortem examination was performed whenever possible. RESULTS: Since 1982, 110 fetal heart defects have been detected: 94 were diagnosed by means of fetal echocardiography (in 21/94 an autopsy was carried out) and 16 were directly observed at the post-mortem (spontaneous or voluntary abortions not previously referred). The heart defects most commonly observed were the atrioventricular (14.5%), ventricular (9.0%), and atrial (7.2%) septal defects, the absent left atrioventricular connection (8.1%), and atrial isomerism (6.3%). The congenital heart defects diagnosed in utero vary from those observed in the newborn and infants in terms of distribution (because of difficulties in diagnosis, selection of pregnancies, and differences in manifestation) and morphology (because of the coexistence with other extracardiac malformations, the changes due to altered fetal hemodynamics, and the intrauterine evolution of the morphology of cardiac defects). CONCLUSIONS: Heart defects observed in utero have a peculiar prevalence and a different morphology in respect to their infantile counterparts and can be followed in their morphologic evolution.

Regression of post-Fontan protein-losing enteropathy. After surgical correction of hemodynamic faults other than high right atrial pressure.

We describe a case of protein-losing enteropathy after a Fontan operation, in the absence of high right atrial pressure. Although partial regression of protein-losing enteropathy was obtained with high doses of cortisone, complete resolution of the phenomenon was accomplished only after surgical closure of a left-to-right shunt through the pulmonary valve.

Myocardial scintigraphy with 99mTc-sestamibi in children with Kawasaki disease.

Kawasaki disease (KD) is a systemic vasculitis syndrome of early childhood. It involves particularly the coronary arteries and may cause aneurysms and thrombotic occlusions. Echocardiography is the most useful method of detecting coronary aneurysms. Nevertheless, obstructive lesions are difficult to evaluate and often need invasive coronary angiography. An important feature of this disease is the possibility of finding coronary pathology several years after the onset. This characteristic makes KD an important cause of coronary artery disease (CAD) in young adults. Thus patients with KD and previously diseased coronary arteries should be kept under long-term control. However, coronary angiography is invasive and cannot be performed repeatedly, especially in young patients. As an alternative, thallium 201 scintigraphy has been employed, but its low-energy photons are suboptimal for standard gamma-camera imaging, particularly in children aged less than three years. To verify the usefulness of a noninvasive assessment of myocardial perfusion, the authors used rest and dipyridamole 99mTc-Sestamibi scan in 15 children (ranging from one to six years of age) with Kawasaki's cardiac involvement. Coronary aneurysms have been demonstrated by echocardiography in 12 patients; 8 patients were also submitted to cardiac catheterization. The sensitivity of 99mTc-Sestamibi imaging for detection of overall coronary lesions was 88% and the specificity was 93%. These data suggest that rest/dipyridamole 99mTc-Sestamibi scintigraphy is an accurate and noninvasive method for the detection and follow-up of Kawasaki's cardiac damage even in patients aged one year.

Analysis of the elastin gene in 60 patients with clinical diagnosis of Williams syndrome.

Williams syndrome (WS) is caused by deletion of the elastin (ELN) gene. We have analyzed an intragenic restriction fragment length polymorphism (RFLP) and the gene dosage of ELN using a new probe (FP4) in a series of 60 sporadic patients with a clinical diagnosis of WS. Deletion of the ELN gene was shown in 54 cases, while clinical revaluation of the 6 patients without the deletion did not confirm the diagnosis of WS. These results support the genetic homogeneity of WS, and the high accuracy of ELN molecular analysis, which can be confidenty used for providing genetic counselling to WS families.

Prenatal echocardiographic diagnosis of right atrial isomerism.

A prenatal diagnosis of right atrial isomerism is often inferred through the recognition of a constellation of cardiac anomalies on the four-chamber view or by the detection of visceral heterotaxy and asplenia. However, the actual occurrence of discordance between the arrangement of the atria and thoracic and abdominal organs makes the identification of the morphology of both atrial appendages the only reliable way to make a final diagnosis of atrial isomerism. Three cases of right atrial isomerism with visceral heterotaxy and a complex cardiac defect, diagnosed in utero by cross-sectional and colour flow Doppler echocardiography, are reported. In all the patients, the right atrial isomerism was associated with an atrioventricular septal defect, a single aortic outlet from the right ventricle, and total anomalous venous return. The diagnosis of right atrial isomerism, always confirmed by neonatal re-evaluation and/or by post-mortem examination, was made through identifying two pyramidal atrial appendages in an echocardiographic transverse plane at the level of the atria and of the origin of the great arteries. This report demonstrates that a final intrauterine diagnosis of atrial isomerism is possible, whatever the visceral situs is.

[Dysplasia of both the components of the atrioventricular valve in atrioventricular septal defects]. / Displasia di entrambe le componenti della valvola atrioventricolare nei difetti del setto atrioventricolare.

BACKGROUND: A spectrum of anomalies of the atrioventricular valves, characterised by decreasing grades of leaflet differentiation from the tension apparatus and the ventricular wall, is included under the common heading of "Atrioventricular Valve Dysplasia". This concept has been further supported by the observation that tricuspid and mitral valve dysplasia frequently occur in the same heart. Although the general features of valvular dysplasia are the same in the two atrioventricular valves, there are side-specific patterns such as grade III dysplasia (and Ebstein's anomaly as well) in the right valve and mitral arcade in the left one. CLINICAL CASE: The common nature of "Atrioventricular Valve Dysplasia" was confirmed by the observation of a newborn infant affected by atrioventricular septal defect with separate orifices. By means of both pre- and post-natal echocardiography, a diagnosis of Ebstein-like dysplasia of the right atrioventricular component, and of marked regurgitation of the left one was made. At the post-mortem examination, a diagnosis of grade III dysplasia of the right valvular component and of grade II dysplasia of the left one was confirmed. REVIEW OF THE LITERATURE: Revision of the cases of atrioventricular septal defect with Ebstein-like dysplasia of the right valvular component disclosed that regurgitation of the left component frequently occurred, and that in one instance it was so severe as to require surgery. It may be inferred that in some cases, as in the one herein reported, such regurgitation could be due to a valvular dysplasia. CONCLUSIONS: The simultaneous presence of dysplasia of both valvular components of a common atrioventricular orifice further validates the concept of "Atrioventricular Valve Dysplasia". Pediatric cardiologists observing patients with atrioventricular septal defect and Epstein-like dysplasia of the right atrioventricular component should be aware of the possibility of a pathologic change in both the valvular components and accordingly plan the correct surgical approach.

Radioisotope assessment of heart damage in hypertransfused thalassaemic patients.

Twenty-five thalassaemic patients treated with repeated blood transfusion (BT) and intensive iron removal therapy were studied by echocardiography and rest/stress equilibrium gated radionuclide angiocardiography (EGNA). Stress left ventricular ejection fraction (LVEF) showed an important negative correlation with number of BTs (r = -0.75). Abnormal values of stress LVEF were measured after 200 BTs: these data demonstrate the effectiveness of stress LVEF in the follow-up of patients who have undergone repeated BTs and the clinical importance of intensive chelation therapy. Peak filling rate did not show diagnostic value in the early detection of iron cardiotoxicity. However, its inverse correlation with BT (r = -60) indicates that iron overload depresses the diastolic parameters.

[The diagnostic and therapeutic utility of adenosine triphosphate in supraventricular tachyarrhythmias in childhood]. / Utilità diagnostica e terapeutica dell'adenosina-trifosfato nelle tachiaritmie sopraventricolari dell'età pediatrica.

The diagnostic and therapeutic utility of adenosine triphosphate (ATP) in pediatric age was investigated in fifteen children aged 4 days-16 years (mean age 6.4 years) observed for paroxysmal (Group A-9 pts) or incessant (Group B-6 pts) tachycardia. Twelve patients underwent transesophageal electrophysiological study. ATP was given as an intravenous bolus (0.075-0.5 mg/Kg). In Group A patients, ATP resulted in termination of spontaneous or induced tachycardia, and in all cases interruption in anterograde limb of the re-entry circuit occurred. In Group B patients, ATP induced transient atrioventricular block with persistence of atrial tachycardia, suggesting the atrial origin of the arrhythmia. No adverse haemodynamic effects were observed in any patient. We conclude that in pediatric age ATP must be considered the drug of first choice for junctional reciprocating tachycardias because of its efficacy, short mid-life and insignificant side-effects. Furthermore, it represents an effective diagnostic test for differentiating between junctional reciprocating tachycardias and atrial ectopic tachycardias.

Altered cardiac repolarization during exercise in congenital aortic stenosis.

The incidence of sudden death in children with congenital aortic stenosis (CAS) varies between 4 and 20%. In several syndromes sudden death is associated with a long QT interval in the electrocardiogram (ECG). The aim of the study was to evaluate the cardiac repolarization in CAS during stress. We included 40 children and young persons, 20 with CAS and 20 healthy controls. All underwent echocardiographic study and treadmill stress test. The QT and relative RR intervals were measured in leads II and V6 at rest and during exercise at preselected heart rates. Mean values of QT were compared by analysis of variance, Student's t-test, and linear regression method. No statistically significant differences in the resting ECG were found between the two groups, whereas during exercise the mean QT of the CAS group was significantly longer than in the controls (p < 0.05), except at a heart rate of 140 +/- 5. Our study demonstrates that patients with CAS have transiently altered cardiac repolarization when there are sudden variations in heart rate. Such a defect could predispose patients with CAS to fatal arrhythmias and sudden death.

Pathology of atrioventricular valve dysplasia.

The congenital heart disease series of the Pathological Museum at La Sapienza University of Rome was revised in order to detect specimens featuring atrioventricular valve dysplasia (AVVD) in fetuses and infants. Selected for study were 67 specimens from a collection of 667 hearts: there were 36 cases of isolated tricuspid valve dysplasia (TVD), 11 cases of isolated mitral valve dysplasia (MVD), and 20 cases of combined atrioventricular valve dysplasia. All the valves were graded according to Becker's criteria, which were morphometrically validated. There is an increasing degree of dysplasia in terms of differentiation and detachment of the valve from the ventricular wall. The concept of AVVD is supported by a substantial morphologic and morphometric analogy between TVD and MVD, in spite of some peculiarities of each grade and of side-specific anomalies ("mitral arcade" on the left side and grade III dysplasia on the right one), probably attributable to differences in the embryonic development of the two valves. AVVD is sometimes associated with dysplasia of the semilunar valves, in the setting of a polyvalvular disease of possible genetic origin. More often it is combined with other defects that cause ventricular overload. In such cases, AVVD usually occurs within the overloaded cardiac section, as if it were a result of mechanical stress.