Is a shorter atrioventricular septal length an intermediate phenotype in the spectrum of nonsyndromic atrioventricular septal defects?

BACKGROUND: Atrioventricular septal defects (AVSDs) account for 7% of all congenital cardiovascular malformations. The atrioventricular septum (AVS) is the portion of the septal tissue that separates the right atrium from the left ventricle; deficiency of the AVS contributes to the AVSD phenotype. A study of case and control families was performed to identify whether an intermediate phenotype consisting of a shortened AVS existed in relatives of children with AVSDs. METHODS: AVS length (AVSL) was measured on the echocardiograms of clinically unaffected parents and siblings from families that were identified through children with nonsyndromic AVSDs and in families with no histories of congenital heart disease. RESULTS: No significant differences were seen between case and control family members in terms of gender, age, weight, and height. AVSLs were significantly shorter in case parents compared with control parents. Similar findings were noted within the sibling groups. There was significant evidence for two-component distributions in the case parent, case sibling, and control sibling groups after standardizing AVSL for age and body surface area. Heritability of AVSL standardized for age and body surface area was 0.82 and 0.71 in nonsyndromic case and control families, respectively. CONCLUSIONS: Evidence for two-component distributions from the analysis of AVSL standardized for age and body surface area for case parents and case siblings suggests the presence of an intermediate phenotype for nonsyndromic AVSD. The high heritability in the control families suggests that there may be polygenic involvement in the determination of AVSL. Broadening the definition of AVSD to include those with shortened AVSL may increase the power of genetic association and mapping studies to identify susceptibility genes for AVSD.

Acute physiological effects of packed red blood cell transfusion in preterm infants with different degrees of anaemia.

OBJECTIVE: The safe lower limit of haematocrit or haemoglobin that should trigger a red blood cell (RBC) transfusion has not been defined. The objective of this study was to examine the physiological effects of anaemia and compare the acute responses to transfusion in preterm infants who were transfused at higher or lower haematocrit thresholds. METHODS: The authors studied 41 preterm infants with birth weights 500-1300 g, who were enrolled in a clinical trial comparing high ('liberal') and low ('restrictive') haematocrit thresholds for transfusion. Measurements were performed before and after a packed RBC transfusion of 15 ml/kg, which was administered because the infant's haematocrit had fallen below the threshold defined by study protocol. Haemoglobin, haematocrit, RBC count, reticulocyte count, lactic acid and erythropoietin were measured before and after transfusion using standard methods. Cardiac output was measured by echocardiography. Oxygen consumption was determined using indirect calorimetry. Systemic oxygen transport and fractional oxygen extraction were calculated. RESULTS: Systemic oxygen transport rose in both groups following transfusion. Lactic acid was lower after transfusion in both groups. Oxygen consumption did not change significantly in either group. Cardiac output and fractional oxygen extraction fell after transfusion in the low haematocrit group only. CONCLUSIONS: These study's results demonstrate no acute physiological benefit of transfusion in the high haematocrit group. The fall in cardiac output with transfusion in the low haematocrit group shows that these infants had increased their cardiac output to maintain adequate tissue oxygen delivery in response to anaemia and, therefore, may have benefitted from transfusion.

The modified Fontan procedure and prolonged pleural effusions.

The modified Fontan procedure may be complicated by prolonged pleural drainage. Predisposing factors are not fully understood. This study examines perioperative variables associated with prolonged effusions. We examined the Fontan procedure in 41 patients. Mean age was 45 months (range, 9 to 113 months). Mean weight was 14.7 kg (range, 6.9 to 30.4 kg). Diagnoses included tricuspid atresia in 29 per cent, pulmonary atresia in 12 per cent, and double-outlet right ventricle in 12 per cent. Fontan revisions were excluded. The extracardiac Fontan was performed in 22 patients (54%) and the lateral tunnel (LT) in 18 (44%). Fenestration was performed in 56 per cent. Ten patients (24%) had prolonged pleural effusions. Mean chest tube output (24.2 vs 14.1 mL/kg/d, P < 0.01), days with chest tubes (10.2 vs 5.8 days, P < 0.01), and length of stay (20.8 vs 8.13 days, P < 0.01) were significantly greater in those with effusions. Preoperative mean pulmonary artery pressure was higher in patients with prolonged effusions (12.7 vs 9.90 mmHg, P = 0.001). No other factors were identified as risk factors. Prolonged pleural effusions (greater than 14 days) are common after the modified Fontan procedure. A higher preoperative mean pulmonary artery pressure may be predictive of these effusions. Fenestration, type of Fontan reconstruction, and size of extracardiac conduit did not predispose to postoperative effusions.

Association between a leukotriene C4 synthase gene promoter polymorphism and coronary artery calcium in young women: the Muscatine Study.

OBJECTIVE: A majority of the recognized risk factors for atherosclerosis and the development of cardiovascular disease have been derived from the study of older populations who have already manifested clinical symptoms. If risk factors can be identified earlier in life, such as genetic variation, preventive measures may be taken before overt symptoms of pathology have manifested, and when treatments may be most effective. METHODS AND RESULTS: In an effort to identify individuals at increased risk for cardiovascular disease, we genotyped 732 members of the Muscatine Study Longitudinal Adult Cohort for candidate genetic markers associated with several pathogenetic processes. We identified age-adjusted increased risks for coronary artery calcium (OR 4.29; 95% CI 1.78, 10.31) and increased mean carotid artery intimal-medial thickness associated with the (-444)A>C promoter polymorphism of Leukotriene C4 Synthase (LTC4S) in women. There were no similar associations in men. CONCLUSIONS: LTC4S plays a key role in the process of inflammation as the rate limiting enzyme in the conversion of arachidonic acid to cysteinyl-leukotrienes, important mediators of inflammatory responses. The (-444)C variant upregulates LTC4S mRNA expression, increasing the synthesis of proinflammatory leukotrienes. Our results support genetic variation modifying inflammatory pathways as an important mechanism in the development of atherosclerosis.

Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants.

OBJECTIVE: Although many centers have introduced more restrictive transfusion policies for preterm infants in recent years, the benefits and adverse consequences of allowing lower hematocrit levels have not been systematically evaluated. The objective of this study was to determine if restrictive guidelines for red blood cell (RBC) transfusions for preterm infants can reduce the number of transfusions without adverse consequences. DESIGN, SETTING, AND PATIENTS: We enrolled 100 hospitalized preterm infants with birth weights of 500 to 1300 g into a randomized clinical trial comparing 2 levels of hematocrit threshold for RBC transfusion. INTERVENTION: The infants were assigned randomly to either the liberal- or the restrictive-transfusion group. For each group, transfusions were given only when the hematocrit level fell below the assigned value. In each group, the transfusion threshold levels decreased with improving clinical status. MAIN OUTCOME MEASURES: We recorded the number of transfusions, the number of donor exposures, and various clinical and physiologic outcomes. RESULTS: Infants in the liberal-transfusion group received more RBC transfusions (5.2 +/- 4.5 [mean +/- SD] vs 3.3 +/- 2.9 in the restrictive-transfusion group). However, the number of donors to whom the infants were exposed was not significantly different (2.8 +/- 2.5 vs 2.2 +/- 2.0). There was no difference between the groups in the percentage of infants who avoided transfusions altogether (12% in the liberal-transfusion group versus 10% in the restrictive-transfusion group). Infants in the restrictive-transfusion group were more likely to have intraparenchymal brain hemorrhage or periventricular leukomalacia, and they had more frequent episodes of apnea, including both mild and severe episodes. CONCLUSIONS: Although both transfusion programs were well tolerated, our finding of more frequent major adverse neurologic events in the restrictive RBC-transfusion group suggests that the practice of restrictive transfusions may be harmful to preterm infants.

Rapid full volume data acquisition by real-time 3-dimensional echocardiography for assessment of left ventricular indexes in children: a validation study compared with magnetic resonance imaging.

OBJECTIVE: We sought to assess the feasibility, accuracy, and reproducibility of a rapid full volume acquisition strategy using real-time (RT) 3-dimensional (3D) echocardiography (3DE) for measurement of left ventricular (LV) volumes, mass, stroke volume (SV), and ejection fraction (EF) in children. METHODS: A total of 19 healthy children (mean 10.6 +/- 2.8 years, 11 male and 9 female) were prospectively enrolled in this study. RT 3DE was performed using an ultrasound system to acquire full volume 3D dataset from the apical window with electrocardiographic triggering in 8 s/dataset. The images were processed offline using software. The LV endocardial and epicardial borders were traced manually to derive LV end-systolic volume, end-diastolic volume, mass, SV, and EF. Magnetic resonance imaging (MRI) studies were performed on a 1.5-T scanner using a breath hold 2-dimensional cine-FIESTA (fast imaging employing steady-state acquisition) sequence. RESULTS: All RT 3DE and MRI data were acquired successfully for analysis. Measurements of LV end-systolic volume, end-diastolic volume, mass, SV, and EF by RT 3DE correlated well by Pearson regression ( r = 0.86-0.97, P < .001) and agreed well by Bland-Altman analysis with MRI. The interobserver and intraobserver variability of RT 3DE measurements were less than 5%. CONCLUSIONS: This prospective study demonstrated that RT 3DE measurements of LV end-systolic volume, end-diastolic volume, mass, SV, and EF in children using rapid full volume acquisition strategy are feasible, accurate, and reproducible and are comparable with MRI measurements.

Influence of body size and section level on calcium phantom measurements at coronary artery calcium CT scanning.

PURPOSE: To determine whether differences in body mass index (BMI) and image section levels representing the proximal through the distal sections of the heart are associated with attenuation differences in images of calcium phantoms scanned during computed tomographic (CT) imaging of study subjects. MATERIALS AND METHODS: Mean attenuation values for three calcium phantoms (each with a different calcium hydroxyapatite concentration), as measured at each of four different image section levels, were obtained for 691 participants in the Muscatine CT Vascular Calcium Study. The subjects were grouped according to sex-specific BMI quartiles, and the degree of attenuation in each phantom was investigated as a function of image section level and BMI quartile. Spearman rank order correlation coefficients and one-, two-, and three-factor repeated-measures analysis of variance were used to examine the association between section level and BMI and the mean phantom attenuations. RESULTS: Attenuation was, for the most part, significantly associated with both section level (P <.005) and BMI quartile (P <.0025-.05). The degree of attenuation tended to decrease in images obtained at the more distal cardiac levels and to increase with increasing BMI quartile. CONCLUSION: Differences in attenuation related to BMI and image section level appear to have a significant effect on current calcium scoring methods.

Congenital heart disease in adults: catheterization laboratory considerations.

Congenital heart defects are the most common birth defects and represent an increasing proportion of adolescent and adult patients followed by cardiologists. While many of these patients have undergone successful palliative or corrective surgery with excellent functional results, most of them still require careful follow-up. Further, even complex lesions may first be diagnosed in adolescence and adulthood. Therefore, cardiologists caring for adults need to become more familiar with these defects. Assessment of the patient with known or suspected congenital heart defects requires a careful history, physical examination, and noninvasive assessment. In addition, the catheterization laboratory remains a critical venue for diagnosis and, increasingly, therapy. Pressure measurements, oximetry, and angiography remain cornerstones of diagnosis in selected patients and a variety of interventional procedures have become viable therapeutic alternatives in both pre- and postoperative patients.

Fat-free mass as a determinant of left ventricular mass in children: The Muscatine Study.

To assess the relationship of somatic growth to heart growth, associations were examined among body composition, blood pressure, androgens, sexual maturation, and left ventricular mass (LVM) during early puberty in 123 children, 7-12 years of age. All subjects underwent anthropometry, random-zero blood pressure measurements, hormone determination of androgens, physician's examination to determine sexual maturation, and echocardiographic examinations. Subjects then repeated these procedures 1 year later. Data were examined cross-sectionally (year 1, year 2) and longitudinally (Δ = year 2 minus year 1). The strongest correlations with LVM were among weight and fat-free mass (FFM) (r = 0.60 to 0.83). In males, cross-sectional predictors of LVM were FFM and stage of sexual maturation (r2 = 0.49 to 0.65). Δ LVM was best predicted in males by Δ testosterone and Δ weight (r2 = 0.22). In females, FFM was the strongest cross-sectional predictor of LVM (r2 = 0.70). Δ LVM was best predicted in females by Δ FFM and Δ height (r2 = 0.27). When males and females were pooled, gender did not predict LVM in any of the models. The results suggest that FFM is an important predictor of LVM in circumpubertal children. Boys and girls do not significantly differ in LVM once normalized for FFM. © 1996 Wiley-Liss, Inc.