Factor V 1691 G-A mutation in children with intracardiac thrombosis: a prospective study.

UNLABELLED: The objective of this study was to determine the association between intracardiac thrombosis and hereditary causes of thrombophilia, including factor V 1691 G-A (factor V Leiden, FVL) and prothrombin 20210 G-A mutations. Over a period of 3 y, genetic risk factors were evaluated in 13 consecutive children (mean age 6.27 +/- 5.44 y) with intracardiac thrombosis, diagnosed by cross-sectional echocardiography. Thrombi were localized in the left heart in four patients and the right heart in nine patients. All children had predisposing factors for thrombus formation: ventriculoatrial shunt for hydrocephalus (n = 3), indwelling catheter for chemotherapy (n = 5), cardiomyopathy (n = 2), sepsis (n = 1), homocystinuria (n = 1) and tetralogy of Fallot (n = 1). Six of the 13 children with intracardiac thrombosis were heterozygotes for FVL mutation. Three of these six children with FVL mutation had ventriculoatrial shunt for hydrocephalus, two children had cardiomyopathy and one had sepsis. None of the patients carried the prothrombin 20210 G-A mutation. CONCLUSION: It is recommended that FVL mutations should be investigated in all cases of intracardiac thrombosis irrespective of whether or not a predisposing factor is identified. When a predisposing factor is found antithrombotic prophylaxis may be considered in patients carrying the FVL mutation.

QRS axis in isolated perimembranous ventricular septal defect and influences of morphological factors on QRS axis.

To detect the frequency of left axis deviation (LAD) in isolated perimembranous ventricular septal defects (VSD) we retrospectively analyzed electrocardiograms of 59 patients, aged 8 months to 15 years. Patients were grouped into those having ventricular septal aneurysm (VSA) formation (n:20) and those who did not have VSA (n:39). Patients with VSA were then stratified into 2 groups according to the presence of left ventricular-to-right atrial (LV-RA) shunt. Four hundred healthy children served as the control group. We found that 12 (20.3%) of 59 patients with isolated perimembranous VSD had a LAD. Five of 6 patients with perimembranous outlet VSD and 6 with perimembranous inlet VSD had abnormal LAD with a qR pattern in I and aVL and rS in aVF. Abnormal LAD was more prevalent in patients with VSA (40%) than without VSA (7.7%) (P <.01). We also found that mild right ventricular hypertrophy (RVH) with the rsR' or rSR' pattern in V1 was more frequent in patients with VSA, especially those who had LV-RA shunt. However, we could not find significant difference between patients with or without LV-RA shunt for the incidence of abnormal LAD and mild RVH. Localization of perimembranous VSD was not found to have an effect on frequency of abnormal LAD and mild RVH in this patient group. In patients with clinical findings of VSD, the existence of abnormal LAD especially if it is associated with mild RVH, should raise the possibility of perimembranous VSD with VSA formation.

Isolated recurrent pericarditis in a patient with familial Mediterranean fever.

Familial Mediterranean fever (FMF) should be kept in mind in the differential diagnosis of recurrent pericarditis and mutation analysis should be considered, especially in patients of Mediterranean origin.

Poststreptococcal reactive arthritis: clinical course and outcome in 15 patients.

Patients with Group A beta-hemolytic streptococcal infection and articular disease, who do not fulfill the modified Jones criteria for diagnosis of acute rheumatic fever (ARF), have been classified as having poststreptococcal reactive arthritis (PSRA). We reviewed the clinical characteristics, laboratory findings and outcome of 15 patients with PSRA. None of these patients had clinical evidence of carditis. The pattern of joint involvement was variable and included arthritis in five patients and arthralgia in the remaining ten patients. Nine patients were treated with salicylates for one to 16 weeks; the others recovered spontaneously. Usually, the patients with arthralgia responded promptly to salicylates, while the response was poor in patients with arthritis. One patient with monoarthritis developed carditis nine months after his first arthritis attack. Another patient presenting with monoarthritis later had two additional episodes of poststreptococcal reactive arthralgia. It seems there is a wide spectrum of poststreptococcal rheumatic diseases, and patients with PSRA are also at risk for cardiac disease; therefore, prophylactic antibiotic therapy should be considered in these patients.

Effects of cisapride on ventricular repolarization in children.

Life-threatening ventricular dysrhythmias mainly attributed to QTc prolongation have been reported in adults and children who were using cisapride, a prokinetic agent that facilitates gastrointestinal motility. Recent adult and paediatric case reports have suggested an association of malignant ventricular dysrhythmias with administration of cisapride in conjunction with drugs that inhibit its cytochrome P-450 metabolism. Therefore, to analyse the time- and dose-related effects of cisapride on ventricular repolarization, we prospectively studied infants and children receiving cisapride with no concomitant medications. Standard 12-lead resting ECGs were obtained from 38 patients (mean age: 6.6 +/- 4.4 y) before the first dose of cisapride (0.8-1.2 mg/kg/d) therapy, and 3 d, 7 d and 1 mo after the first dose of continuing cisapride therapy. The corrected QT interval (QTc), dispersion of QT and QTc (QTD, QTcD) were calculated. Patients were divided into two groups according to dose of cisapride: Group 1 (n = 22) (0.8 mg/kg/d), Group 2 (n = 16) (1.2 mg/ kg/d). Data obtained from these patients were compared with a control group consisting of 372 normal children. No clinical adverse effects such as palpitations, presyncope or syncope were noted during the study. Baseline QTc, QTD and QTcD measurements of the study group were not different from those of the control group. Mean QTc values of the study group on days 7 and 30 of cisapride therapy were found to be significantly higher than those of the control group (p < 0.001 and <0.0001, respectively). Mean QTc values of the study group on days 7 and 30 of therapy were also significantly higher than those of baseline value (p < 0.01 and <0.001, respectively). Mean QTD and mean QTcD values that were recorded throughout the cisapride treatment in the study group were not found to be different from the baseline values and the values of the controls. Mean QTD and QTcD were also not found to be different between Groups 1 and 2. However, mean QTc was found to be more significantly increased from baseline at the first month of therapy in Group 2 (p < 0.05). The results of this study suggest that cisapride treatment cause prolongation of ventricular repolarization without causing increased heterogeneity of repolarization (QT dispersion). However, the clinical significance of this effect is unclear, because all the patients in this study group remained asymptomatic, without signs of dysrhythmia.

Echocardiographic, morphologic, and geometric variations of the left ventricular outflow tract: possible role in the pathogenesis of discrete subaortic stenosis.

Although the clinical features and natural course of discrete subaortic stenosis (DSS) are well defined, the etiology remains speculative. The purpose of this study was to identify the echocardiographic, morphologic, and geometric variations of the left ventricular outflow tract associated with DSS in children and to determine whether these variations have a role in the pathogenesis of DSS. The aortoseptal angle (ASA), mitral-aortic valve separation (MAS), and the size of the aortic annulus were determined in two groups of children. Group 1 comprised 11 patients with isolated DSS, who were compared with an age- and body surface area- (BSA) matched healthy children (Group 1A, n: 20). Group 2 comprised 10 patients with DSS and ventricular septal defect (VSD). Group 2 was compared with an age- and BSA-matched patients with isolated perimembranous VSD (Group 2A, n: 22). Measurements were carried out from previously recorded echocardiographic studies. The ASA was steeper (119.3 +/- 6.1 degrees vs 137.5 +/- 5.6 degrees , p < 0.001), and the MAS was wider (6.1 +/- 1.6 vs 3.2 +/- 0.7 mm, p < 0.001) in patients with isolated DSS than in healthy control subjects. Similar differences were found between patients in Group 2 and Group 2A; the ASA was steeper (122.2 +/- 6.5 degrees vs 141.3 +/- 5.0 degrees, p < 0.001), and the MAS was wider (5.8 +/- 1.5 vs 3.8 +/- 1.1 mm, p < 0.001). The size of the aortic annulus was not different among the four study groups. Although the MAS was significantly wider in patients with DSS, there was significant overlap in MAS between patients and controls. However, if an ASA < or = 130 degrees was chosen as a predictive variable, it was found to be a highly sensitive, specific, and positive predictive marker for the development of DSS. This study demonstrates that DSS is associated with a steeper ASA, and a wider MAS, in patients with or without associated VSD. These morphologic abnormalities, especially a steeper ASA, may be risk factors for the development of DSS.

Plasma endothelin-1 levels in patients with left-to-right shunt with or without pulmonary hypertension.

The aim of this study was to evaluate the role of endothelin-1 (ET-1) in pathophysiology of pulmonary hypertension (PH) secondary to congenital heart disease with left-to-right shunt. Twenty-three children (12 male, 11 female) aged 0.58-13 years were enrolled the study. Blood samples were drawn from superior vena cava, right atrium, right ventricle, pulmonary artery and pulmonary wedge or pulmonary vein during cardiac catheterization. Plasma ET-1 levels were assayed by ELISA. Patients were divided into two groups according to the presence or absence of PH. Plasma ET-1 levels of the study group were compared to the peripheral venous and arterial ET-1 levels of 11 healthy infants and children (aged 0.75-13 years). Plasma ET-1 levels in patients with left-to-right shunt were found significantly higher than those of controls. However, plasma ET-1 levels were similar between the two groups of the patients. Pulmonary venous ET-1 levels were higher than the levels of superior vena cava, this suggested an increased production of ET-1 in pulmonary vascular bed in patients with PH. No correlations were found between plasma ET-1 levels and pulmonary arterial pressure, pulmonary vascular resistance and pulmonary blood flow in the patients. Plasma ET-1 levels of the patients with left-to-right shunt were increased independently from pulmonary arterial pressure and pulmonary vascular resistance. This increase was related to the production of ET-1 in pulmonary vascular bed in patients with PH. ET-1 could not be found to be directly related to the development of PH in the patients with left-to-right shunt.

QT/corrected QT (QTc) intervals and QT/QTc dispersions in children with chronic renal failure.

UNLABELLED: We aimed to examine QT/corrected QT (QTc) intervals, QT/QTc dispersions (QTD/QTcD) and also the effect of different clinical and laboratory variables on these parameters in children with chronic renal failure. Serum biochemistry, 12-lead electrocardiogram, telecardiogram, and echocardiography were performed in 50 children with chronic renal failure (23 female and 27 male; aged 12.3+/-3.6 years, range 5 to 20 years). None of them had symptoms related to arrhythmias. When compared with a control group (372 children, aged 7 to 18 years, mean 12.4+/-2.6) patients with chronic renal failure had greater QT/QTc intervals and QT/QTc dispersion values (Patient: QT = 360.9+/-53.3; QTc = 438.5+/-33.2; QTD = 42.4+/-20.8; QTcD = 57.5+/-23.8; CONTROL: QT = 325.9+/-24.1; QTc = 398.7+/-19.7; QTD = 29.9+/-10.2; QTcD = 47.3+/-16.6; P<0.01). QT, QTc, and QTcD values were significantly greater in patients who had renal failure duration longer than 2 years. Patients who had impaired left ventricular systolic function on echocardiogram had greater QTc, QTD, and QTcD values. It was found that sex, cardiomegaly on chest X-ray, and left ventricular hypertrophy on echocardiogram were not related to these parameters. It is concluded that, impaired cardiac systolic function and longer renal failure duration are related to an increase in QT, QTc, QTD, and QTcD values and hence these variables may be risk factors for ventricular arrhythmias in uremic patients.

Recurrent pericardial effusion due to gunshot wound of the heart in a hemodynamically stable child--a case report.

A 12-year-old girl presented with recurrent pericardial effusion due to firearm pellet injury to the left ventricle. The pellet was localized by two-dimensional echocardiography within the left ventricular apical wall. Since the patient was asymptomatic, left ventriculotomy was avoided to extract the pellet and only pericardial tube drainage was carried out. A slightly elevated blood lead level of the patient was alarming for potential subsequent lead poisoning due to retained pellets.

Relation of mass/volume ratio to ECG abnormalities and symptoms in children with aortic stenosis/insufficiency.

In this study, to determine whether symptoms and ECG abnormalities relate to left ventricular (LV) mass, volume, and mass/volume (M/V) ratio in children with aortic stenosis (AS) and/or insufficiency (AI), the authors examined 23 patients with echocardiography. LV volumes and mass were calculated with echocardiography. Also, the peak and mean gradients across the aortic valve and left ventricular meridional wall stress (ESWS) were determined by use of echo Doppler techniques. Fourteen patients (mean age 5.84+/-3.49 years) had AS alone. Of these, 14 had symptoms and seven had abnormal-appearing ECGs. Nine patients (mean age 6.91+/-4.35 years) had AS/AI. Of these nine, four had symptoms and two had ECG abnormalities. The authors observed that the incidences of symptoms and ECG abnormalities were higher in the patients with AS than in those with AS/AI. There was no significant correlation between symptoms and ECG abnormalities with peak gradient, mean gradient, valve area, LV mass, volume, and mass/volume ratio in patients with AS/AI. However, significant correlation was found between symptoms and ECG abnormalities and ESWS in AS/AI patients. In conclusion, ECG abnormalities and symptoms do not always indicate the severity of AS and AS/AI.

Dispersion of QT and QTc interval in healthy children, and effects of sinus arrhythmia on QT dispersion.

OBJECTIVE: To determine the normal values of QT and QTc dispersion and the effects of sinus arrhythmia on QT dispersion in healthy children. PATIENTS AND SETTING: The study was carried out in a university hospital on 372 local schoolchildren (200 male, 172 female), aged seven to 18 years. METHODS: The QT and preceding RR intervals of at least one sinus beat were measured manually in a range of nine to 12 leads on standard 12 lead surface ECGs. The corrected QT interval was computed by the method of Bazett. Dispersion of QT and QTc were defined as (1) the difference between the maximum and minimum QT and QTc intervals occurring in any of the 12 leads (QTD and QTcD), (2) the standard deviation of the QT and QTc interval in the measurable leads (QT-SD and QTc-SD). RESULTS: There was no significant difference in QT, QTc, and RR dispersion between girls and boys. Overall 53% of children had sinus arrhythmia. Although QTD and QT-SD were not affected by sinus arrhythmia, both QTcD and QTc-SD were significantly greater in children with sinus arrhythmia than in those without (QTcD: 52.9 (17.4) v 40.9 (13.1); QTc-SD: 17.5 (5.9) v 13.2 (4.0); p < 0.001). CONCLUSIONS: As calculation of QTc dispersion is affected by sinus arrhythmia, which is common in childhood, we suggest that QT dispersion should not be corrected for heart rate in children.

Premature thelarche in Kabuki make-up syndrome.

A 2 year old girl who has Kabuki make-up syndrome with isolated premature thelarche is presented. She has unique ocular abnormalities which have not been reported previously. In the literature at least 85 patients, most of them from Japan, have been reported. This is the first reported non-Japanese Asian case.