Lennie van Osch-Gevers

Reliability of echocardiographic measurements of left cardiac structures in healthy children.

BACKGROUND Echocardiographic measurements are widely used as outcomes of different studies. The aim of this study was to assess intraobserver and interobserver reliability of echocardiographic measurements in healthy children. MATERIALS AND METHODS We studied 28 children, with a median age of 7.5 years, and inter-quartile range from 3 to 11 years. Intraobserver and interobserver reliability were assessed by repeated measurements of the diameters of the aortic root, the left atrium, and left ventricular end-diastolic structure. We also measured the ventricular end-diastolic septal thickness and the end-diastolic thickness of the left ventricular posterior wall. We calculated intraclass correlation coefficients, with corresponding 95% confidence intervals, and computed Bland and Altman plots, permitting us to derive limits of agreement plus or minus 2 standard deviations for the mean differences in cardiac measurements. RESULTS We found high intraobserver and interobserver intraclass correlation coefficient, ranging from 0.91 for ventricular septal thickness, with 95% confidence intervals from 0.78 to 0.96, to 0.99 for the diameter of the aortic root, 95% confidence interval from 0.97 to 1.00. Limits of agreement in the Bland and Altman plots ranged from zero millimetres for left ventricular end-diastolic posterior wall thickness to 1.60 millimeters (6.3%) for left atrial diameter. CONCLUSIONS Our study demonstrated good repeatability and reproducibility for ultrasonic measurements of left cardiac structures in children, showing that values obtained for measurement of these structures in both clinical and epidemiological research projects can be confidently accepted.

Clinical outcome 5 to 18 years after the Fontan operation performed on children younger than 5 years.

OBJECTIVE This study assessed clinical condition at midterm follow-up after total cavopulmonary connection for a functionally univentricular heart performed on children younger than 5 years. METHODS Thirty-four Fontan patients (median age 10.4 years, range 6.8-20.7 years, 22 boys, median follow-up 7.8 years, 5.0-17.8 years) underwent electrocardiography, Holter monitoring, bicycle exercise testing, cardiac magnetic resonance imaging, and N-terminal prohormone brain natriuretic peptide (NT-pro-BNP) analysis. RESULTS Twenty-three patients (68%) were in sinus rhythm. Holter monitoring demonstrated normal mean heart rate, low maximal heart rate, and no clinically significant arrhythmias or sinus node dysfunction. With maximal bicycle ergometry (n = 19), maximum workload (60% of normal), maximum heart rate (90% of normal), and maximal oxygen uptake (69% of normal) were all significantly lower in the Fontan group than in a control group (P < .001). Variables of submaximal exercise indicated less efficient oxygen uptake during exercise in all Fontan patients. Ejection fraction was lower than in control subjects (59% +/- 13% vs 69% +/- 5%, P < .001). Mean end-diastolic and end-systolic volumes and ventricular mass were higher than in control subjects (P < .001). Mean NT-pro-BNP levels were increased relative to reference values, but only 8 patients had levels above the upper reference limit. CONCLUSION At midterm follow-up, Fontan patients were in acceptable clinical condition, with preserved global ventricular function, moderately decreased exercise capacity, and NT-pro-BNP levels within reference range. Systemic ventricular mass was elevated, however, suggesting contractility-afterload mismatch. Long-term consequences for ventricular function merit further investigation.

Growth, obesity, and cardiac structures in early childhood: the Generation R Study.

Cardiac structural adaptations in response to physical growth and obesity in older children have been identified and might have long-term consequences. We examined the associations of growth and obesity with cardiac structures during the first 2 years of life. In a population-based prospective cohort study among 974 children, left atrial diameter, left ventricular diastolic diameter, left ventricular mass, aortic root diameter, and fractional shortening were repeatedly measured by ultrasound at the ages of 1.5, 6, and 24 months. Height, weight, and subcutaneous fat mass were measured at the same visits, and blood pressure was measured at the age of 24 months. Height, weight, body mass index, and body surface area were positively associated with all of the cardiac structures during the first 2 years of life. At the age of 24 months, as compared with normal weight children, obese children had a greater left ventricular mass (1.04 SD score [95% CI: 0.20 to 1.89]) and a higher fractional shortening (0.91 SD score [95% CI: 0.02 to 1.80]). Nonsignificant tendencies were found for left atrial diameter, left ventricular diastolic diameter, and aortic root diameter. Our results suggest that normal variation in growth affects cardiac structures in early life. Overweight and obese children show cardiac adaptations already at the age of 2 years. Further studies are needed to assess whether these structural adaptations influence the risk of cardiovascular disease in later life.

Cardiac structures track during the first 2 years of life and are associated with fetal growth and hemodynamics. The Generation R Study

BACKGROUND The aim of this study is to examine whether cardiac size and function track in early childhood and are associated with fetal and early postnatal growth and blood flow characteristics. METHODS This study was embedded in a population-based prospective cohort study from fetal life onward. Fetal growth and fetal and placental blood flow parameters in second and third trimester of pregnancy were measured by ultrasound and Doppler. Left cardiac structures and shortening fraction were measured postnatally at the ages of 1.5, 6, and 24 months. Analyses were based on 1,001 children. RESULTS Left ventricular mass tended to remain in the lowest and highest quartiles from the age of 1.5 to 24 months (odds ratio 1.70, 95% confidence interval [CI] 1.10-2.63) and 2.15 (95% CI 1.41-3.30), respectively. Similar results were found for aortic root diameter and left atrial diameter. Birth weight was positively associated with aortic root diameter (0.08 mm, 95% CI 0.01-0.17; per SD increase) and left ventricular mass (0.65 g, 95% CI 0.09-1.21; per SD increase). Resistance indices of the umbilical and uterine arteries showed weak tendencies toward inverse associations with left cardiac structures. Fetal cardiac output was positively associated with both left atrial diameter (increase of 1.96 mm, 95% CI 1.28-2.64; per mL/min increase) and left ventricular mass (increase of 1.79 g, 95% CI 0.35-3.22; per mL/min increase). CONCLUSIONS This study suggest moderate tracking of left cardiac structures during the first 2 years and that small size and hemodynamic variations in fetal life have consequences for postnatal cardiac size and function.

Infant Feeding Patterns Are Associated with Cardiovascular Structures and Function in Childhood

Nutrition in infancy seems to be associated with cardiovascular disease and its risk factors in adulthood. These associations may be explained by cardiovascular developmental adaptations in childhood in response to specific infant feeding patterns. The aim of this study was to assess whether duration and exclusivity of breastfeeding and timing of introduction of solid foods affect cardiovascular development in childhood. In a population-based prospective cohort study from fetal life onward, information about duration and exclusivity of breastfeeding and timing of introduction of solid foods was obtained from delivery reports and questionnaires. Blood pressure, carotid-femoral pulse wave velocity (PWV), left atrial diameter (LAD), aortic root diameter (AOD), left ventricular (LV) mass, and fractional shortening (FS) were measured at a median age of 6.0 y (95% range: 5.6-7.4 y). Analyses were based on 5003 children. Age at introduction of solid foods was negatively associated with systolic and diastolic blood pressure at the age of 6 y. Compared with children who had ever been breast-fed, never-breast-fed children had a higher carotid-femoral PWV (β: 0.13 m/s; 95% CI: 0.03, 0.24 m/s), a smaller LAD (β: -0.29 mm; 95% CI: -0.55, -0.03 mm), and less LV mass (β:-1.46 g; 95% CI: -2.41, -0.52 g) at the age of 6 y. Among breast-fed children, duration and exclusivity were not associated with cardiovascular structures or function. Breastfeeding pattern and age at introduction of solid foods were not associated with AOD or FS. Feeding patterns in infancy may influence cardiovascular development in childhood. Further research is required to replicate these findings and to investigate whether these changes contribute to an increased risk of cardiovascular disease in later life.

Maternal anthropometrics in pregnancy are associated with left ventricular mass in infancy. The generation R study

Pregnancy and early life factors may permanently affect left ventricular growth and development in the offspring. The aim of this study was to examine the associations of maternal anthropometrics during pregnancy with left ventricular mass (LVM) in infancy. This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life onwards. Maternal anthropometrics were obtained in early (gestational age <18 wk), mid- (gestational age 18–25 wk), and late (gestational age >25 wk) pregnancy. Echocardiographic follow-up measurements were performed in 791 infants aged 6 wk and 6 mo. We found no associations of maternal height, weight, or body mass index (BMI) measured in early, mid-, and late pregnancy with longitudinally measured left ventricular mass (LVM) from 6 wk to 6 mo. Maternal weight gain until late pregnancy was associated with an increased growth of LVM from 6 wk to 6 mo [difference 0.46 g per week for the highest tertile of weight gain compared with the lowest tertile (p value <0.05)]. We concluded that maternal weight gain until late pregnancy is associated with larger LVM at the age of 6 mo, suggesting that maternal health status during pregnancy may have permanent consequences for LVM in their children. Further studies are needed to identify the underlying causal mechanisms and the long-term consequences.

Parental smoking during pregnancy and cardiovascular structures and function in childhood: The Generation R Study

BACKGROUND Foetal smoke exposure might lead to foetal developmental adaptations that permanently affect the cardiovascular system. We assessed the associations of both maternal and paternal smoking during pregnancy with childhood cardiovascular structures and function. METHOD In a prospective cohort study among 5565 children, we examined whether maternal and paternal smoking during pregnancy are associated with blood pressure, carotid-femoral pulse wave velocity and left cardiac structures and function in 6-year-old children. RESULTS As compared with children from non-smoking mothers, children from mothers who smoked more than 10 cigarettes per day had a higher diastolic blood pressure [difference 1.43 mmHg (95% confidence interval: 0.22, 2.63)]. Maternal smoking during pregnancy was not associated with systolic blood pressure, childhood carotid-femoral pulse wave velocity or left cardiac structures. Maternal smoking of 10 or more cigarettes per day was associated with a higher fractional shortening in childhood [difference 1.01% (95% confidence interval: 0.18, 1.84)]. Among mothers who did not smoke during pregnancy, paternal smoking was associated with aortic root diameter but not with other cardiovascular outcomes. CONCLUSIONS Maternal smoking during pregnancy is associated with higher diastolic blood pressure and fractional shortening, although the effect estimates are small. The stronger effect estimates for maternal smoking compared with paternal smoking might suggest that direct intrauterine adaptive responses are involved as underlying mechanisms.

Glucocorticoid receptor-9beta polymorphism is associated with systolic blood pressure and heart growth during early childhood. The Generation R Study.

BACKGROUND glucocorticoid receptor-9β polymorphism (rs6198) is associated with the susceptibility for cardiovascular disease. AIM to examine whether the GR-9 β variant is also associated with blood pressure and heart growth in early childhood. STUDY DESIGN this study was embedded in a population-based prospective cohort study from fetal life onwards. Analyses were based on 857 children. OUTCOME MEASURES Left cardiac structures (aortic root diameter, left atrial diameter and left ventricular mass), shortening fraction and heart beat were measured postnatally at the ages of 1.5, 6 and 24 months. Blood pressure was measured at 24 months of age. RESULTS the distribution of the GR-9β genotype showed 75.1% homozygous reference, 23.5% heterozygous and 1.4% homozygous variant subjects. No differences in cardiovascular outcomes were observed at the ages of 1.5 and 6 months. At the age of 24 months, homozygous variants showed an increased systolic blood pressure of 2.65 mmHg (95% CI: 0.16, 5.14), an increased heart rate of 9.10 beats per minute (95% CI: 1.28, 16.7) and an increased left ventricular mass of 4.99 g (95% CI: 1.33, 8.65) compared to homozygous references. This means an increase of 2.6%, 8.6% and 16%, respectively. GR-9 β polymorphism was significantly associated with left ventricular mass growth during the first 2 years. CONCLUSION our findings suggest that genetically determined differences in cortisol exposure affect cardiovascular development in early life.

Outcome after reoperation for atrioventricular septal defect repair

Results of surgical repair of atrioventricular septal defect (AVSD), both partial (PAVSD) and complete (CAVSD), have improved. However, reoperation is not uncommon. This report describes our experience in 59 patients who underwent reoperation after AVSD repair, between 1977 and 2008. Thirty-one patients had a PAVSD, 28 had a CAVSD. Mean interval between initial repair and reoperation was 10+/-11 years (PAVSD vs. CAVSD: 13+/-12 vs. 6+/-9 years, P=0.063). Reoperations were required for left atrioventricular valve regurgitation (LAVVR) in 53 patients (combined with right atrioventricular valve regurgitation in 10, atrial septal defect (ASD) in 11, ventricular septal defect (VSD) in 7, left ventricular outflow tract (LVOT) obstruction in 1, and aortic valve stenosis in 1), ASD in 3, and LVOT obstruction in 3. Valve repair was performed in 45 patients and replacement in 8. Repair techniques of the left-sided atrioventricular valve (LAVV) included cleft closure in 44 patients, commissuroplasty in 19, and annuloplasty in 1. Freedom from additional reoperation was 85%, and 80% at 5 and 15 years. Hospital mortality was 3%. Overall survival was 91%, and 86% after 5 and 15 years. The most common indication to undergo reoperation is LAVVR. Reoperation is safe and in the majority of cases, a durable repair of the LAVV can still be achieved.

Pulmonary artery size and function after Fontan operation at a young age

To assess pulmonary artery (PA) size, flow variables, and wall shear stress (WSS) in patients after Fontan operation at a young age.