Assessment of the mechanism of mitral valve prolapse in children: An echocardiography study.

BACKGROUND: The high complexity of mitral valve anatomy and function in mitral valve prolapse (MVP) is not yet fully understood. OBJECTIVE: The purpose of this study was to analyze each part of the mitral valve apparatus in children to determine its impact on the presence of MVP and to assess the interaction between the coaptation length (CL) and mitral regurgitation severity. METHODS: We prospectively analyzed transthoracic echocardiograms of 60 patients with MVP (mean age 9.8 ± 3.1 years). We compared these patients with 60 control patients without disease. We determined length of leaflets, chordal length, tenting area, coaptation CL, the intrapapillary muscle distance (IPMD) and relation between CL and severity of mitral regurgitation (MR). RESULTS: For patients with MVP, the posterior mitral leaflet (PML) was significantly enlarged 13.9 ± 4.1 mm versus 10.7 ± 3.5 mm (p < .01), the primary chordal length was significantly decreased 15.4 ± 3.61 mm versus 17.6 ± 3.8 mm (p < .02), and IPMD was significantly greater 18.1 ± 2.7 mm versus 16.6 ± 4.3 mm (p < .03). The difference between CL for both the anterior and posterior mitral leaflets correlated positively with MR (r = .249, p < .05). A greater than 4 mm CL correlated with at least MR (sensitivity 100%, specificity 72%) and greater than 5 mm correlated with at least moderate MR (sensitivity 100%, specificity 60%). CONCLUSION: The majority of pediatric patients with mitral valve prolapse have structural abnormalities that are defined well by echocardiography. In addition to the presence of prolapse and regurgitation, routine assessment of leaflet length, thickness, chordal length and papillary muscle distance is fundamental for patients with MVP.

Cardiac function in congenital adrenal hyperplasia: a pattern of reversible cardiomyopathy.

OBJECTIVE: To evaluate cardiac function in infants with congenital adrenal hyperplasia (CAH) before and after corticosteroid replacement therapy. STUDY DESIGN: This prospective, case-control study included 9 infants with CAH. Cardiac function was assessed by echocardiography at presentation and after corticosteroid replacement therapy. Six term infants underwent 2 echocardiograms each and served as the control group. Data on fractional shortening (FS), rate-corrected velocity of circumferential fiber shortening (Vcf), wall stress, tissue Doppler indices, myocardial performance index, left ventricular mass, and Vcf/wall stress were obtained. RESULTS: The infants with CAH exhibited myocardial dysfunction at baseline and lower systolic blood pressure (SBP) compared with the control group. FS, a measure of systolic contractility, differed significantly from before to after corticosteroid treatment (mean, 32.3%±4.7% pretreatment, 39.9%±5.0% posttreatment). Vcf, a preload-independent measure of cardiac contractility, also differed significantly before and after treatment (mean, 1.23±0.16 circumferences/second pretreatment, 1.45±0.22 circumferences/second posttreatment). SBP was also lower (mean, 84±9.3 mmHg) and improved with treatment (mean, 95±4.8 mmHg). The control group demonstrated no statistically significant changes in FS, Vcf, or SBP. There was a change in left ventricular mass in the control group between the 2 studies. CONCLUSION: Newborns with CAH have evidence for cardiac dysfunction at baseline that reverses with corticosteroid replacement therapy. These data suggest that corticosteroids play a direct role in modulating cardiac function in the newborn.

Ambient air pollution and cardiovascular malformations in Atlanta, Georgia, 1986-2003.

Associations between ambient air pollution levels during weeks 3-7 of pregnancy and risks of cardiovascular malformations were investigated among the cohort of pregnancies reaching at least 20 weeks' gestation that were conceived during January 1, 1986-March 12, 2003, in Atlanta, Georgia. Surveillance records obtained from the Metropolitan Atlanta Congenital Defects Program, which conducts active, population-based surveillance on this cohort, were reviewed to classify cardiovascular malformations. Ambient 8-hour maximum ozone and 24-hour average carbon monoxide, nitrogen dioxide, particulate matter with an average aerodynamic diameter of <10 microm (PM(10)), and sulfur dioxide measurements were obtained from centrally located stationary monitors. Temporal associations between these pollutants and daily risks of secundum atrial septal defect, aortic coarctation, hypoplastic left heart syndrome, patent ductus arteriosus, valvar pulmonary stenosis, tetralogy of Fallot, transposition of the great arteries, muscular ventricular septal defect, perimembranous ventricular septal defect, conotruncal defects, left ventricular outflow tract defect, and right ventricular outflow defect were modeled by using Poisson generalized linear models. A statistically significant association was observed between PM(10) and patent ductus arteriosus (for an interquartile range increase in PM(10) levels, risk ratio = 1.60, 95% confidence interval: 1.11, 2.31). Of the 60 associations examined in the primary analysis, no other significant associations were observed.

Prevalence of congenital heart defects in metropolitan Atlanta, 1998-2005.

OBJECTIVE: To determine an accurate estimate of the prevalence of congenital heart defects (CHD) using current standard diagnostic modalities. STUDY DESIGN: We obtained data on infants with CHD delivered during 1998 to 2005 identified by the Metropolitan Atlanta Congenital Defects Program, an active, population-based, birth defects surveillance system. Physiologic shunts in infancy and shunts associated with prematurity were excluded. Selected infant and maternal characteristics of the cases were compared with those of the overall birth cohort. RESULTS: From 1998 to 2005 there were 398 140 births, of which 3240 infants had CHD, for an overall prevalence of 81.4/10 000 births. The most common CHD were muscular ventricular septal defect, perimembranous ventricular septal defect, and secundum atrial septal defect, with prevalence of 27.5, 10.6, and 10.3/10 000 births, respectively. The prevalence of tetralogy of Fallot, the most common cyanotic CHD, was twice that of transposition of the great arteries (4.7 vs 2.3/10 000 births). Many common CHD were associated with older maternal age and multiple-gestation pregnancy; several were found to vary by sex. CONCLUSIONS: This study, using a standardized cardiac nomenclature and classification, provides current prevalence estimates of the various CHD subtypes. These estimates can be used to assess variations in prevalence across populations, time, or space.

The importance of nomenclature for congenital cardiac disease: implications for research and evaluation.

BACKGROUND: Administrative databases are often used for congenital cardiac disease research and evaluation, with little validation of the accuracy of the diagnostic codes. METHODS: Metropolitan Atlanta Congenital Defects Program surveillance records were reviewed and classified using a version of the International Pediatric and Congenital Cardiac Code. Using this clinical nomenclature as the referent, we report the sensitivity and false positive fraction (1 - positive predictive value) of the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for tetralogy of Fallot, transposition of the great arteries, and hypoplastic left heart syndrome. RESULTS: We identified 4918 infants and foetuses with congenital cardiac disease from the surveillance records. Using only the International Classification of Diseases diagnosis codes, there were 280 records with tetralogy, 317 records with transposition, and 192 records with hypoplastic left heart syndrome. Based on the International Pediatric and Congenital Cardiac Code, 330 records were classified as tetralogy, 163 records as transposition, and 179 records as hypoplastic left heart syndrome. The sensitivity of International Classification of Diseases diagnosis codes was 83% for tetralogy, 100% for transposition, and 95% for hypoplastic left heart syndrome. The false positive fraction was 2% for tetralogy, 49% for transposition, and 11% for hypoplastic left heart syndrome. CONCLUSIONS: Analyses based on International Classification of Diseases diagnosis codes may have substantial misclassification of congenital heart disease. Isolating the major defect is difficult, and certain codes do not differentiate between variants that are clinically and developmentally different.

Impact of educational video on critical congenital heart disease screening.

OBJECTIVE: To assess the status of pulse oximetry screening and barriers to implementing screening programs. METHODS: This was a prospective pre-post intervention survey of nurse managers and medical directors of hospital-based birthing centers in Oregon, Idaho, and Southern Washington. The intervention was a 7-minute video demonstrating and discussing pulse oximetry screening for critical congenital heart disease. RESULTS: Analysis of matched pairs showed a significant increase in the use of pulse oximetry screening during the study period from 52% to 73% (P < .0001). Following implementation of the video, the perception of all queried potential barriers decreased significantly among individuals from hospitals self-identified as nonscreening at baseline. Viewing the educational video was associated with an increase in the percentage of individuals from nonscreening hospitals that rated screening as "very beneficial" (45% vs 90%, P = .0001). CONCLUSIONS: An educational video was associated with improved opinions of pulse oximetry screening among hospitals not currently screening.

Accuracy of plasma B-type natriuretic peptide to diagnose significant cardiovascular disease in children: the Better Not Pout Children! Study.

OBJECTIVES: The purpose of this study was to assess the ability of plasma B-type natriuretic peptide (BNP) to diagnose significant cardiovascular disease (CVD) in the pediatric population. BACKGROUND: BNP has been shown to be reliable in detecting ventricular dysfunction and heart failure in adults. Timely and accurate identification of significant pediatric heart disease is important but challenging. A simple blood test could aid the front-line physician in this task. METHODS: Subjects without a history of heart disease with findings possibly attributable to significant CVD in the acute care setting requiring a cardiology consult were enrolled. Clinicians were blinded to the BNP result, and confirmation of disease was made by cardiology consultation. RESULTS: Subjects were divided into a neonatal (n = 42, 0 to 7 days) and older age group (n = 58, >7 days to 19 years). CVD was present in 74% of neonates and 53% of the older age group. In neonates with disease, median BNP was 526 pg/ml versus 96 pg/ml (p < 0.001) for those without disease. In older children with disease, median BNP was 122 pg/ml versus 22 pg/ml in those without disease (p < 0.001). Subjects with disease from an anatomic defect, a longer hospital stay, or who died had higher BNP. A BNP of 170 pg/ml yielded a sensitivity of 94% and specificity of 73% in the neonatal group and 87% and 70% in the older age group, respectively, using a BNP of 41 pg/ml. CONCLUSIONS: BNP is a reliable test to diagnose significant structural or functional CVD in children. Optimal cutoff values are different from adult values.

Turner syndrome is an independent risk factor for aortic dilation in the young.

OBJECTIVE: Because aortic dilation increases the risk for dissection in the general adult population, and dissection occurs with greater frequency at a young age with Turner syndrome, we studied the prevalence, magnitude, and determinants of aortic dilation in a large group of girls and young women with Turner syndrome. PATIENTS AND METHODS: Participants at annual Turner syndrome society meetings completed a questionnaire regarding their medical history. Echocardiographic measurements of their aorta were converted to z scores by using data from a larger group of normal control female subjects. Bivariable and multivariable analyses evaluated the effects of Turner syndrome features, such as a bicuspid aortic valve, coarctation, growth-hormone therapy, blood pressure, and karyotype, on aortic size. RESULTS: Among 138 individuals with Turner syndrome <18 years old, 49% had the 45,X karyotype, 26% had bicuspid aortic valve, 17% had a history of coarctation, 78% had a history of growth-hormone therapy, and 40% had hypertension. Aortic z scores were calculated by using data from 407 control subjects. Bivariable analyses revealed that a bicuspid aortic valve, growth hormone, and 45,X karyotype predicted a larger proximal aorta at >/=1 level. Multivariable analysis predicted a larger proximal aorta at all of the levels only for bicuspid aortic valve individuals and at the annular level for those who received growth hormone. Importantly, all of the analyses revealed that Turner syndrome predicted a larger proximal aorta independent of these characteristics. CONCLUSIONS: Among young individuals with Turner syndrome, a bicuspid aortic valve predicts a larger proximal aorta, and growth-hormone use may predict a larger aortic annulus. Compared with a control population, Turner syndrome alone is an independent risk factor for aortic dilation.

Population-based perspective of long-term outcomes after surgical repair of partial atrioventricular septal defect.

BACKGROUND: This investigation was designed to determine long-term survival, reoperation rates, and functional status after surgical repair of partial atrioventricular septal defect (PAVSD). METHODS: This population-based cohort study with cumulative, prospective follow-up by questionnaire and medical record review included all patients aged younger than 19 years old in the state of Oregon who underwent surgical repair of a PAVSD from 1958 to 2000. The incidence of early death, late death, and reoperation for left atrioventricular valve pathology were determined. Patient-reported health status as measured by the Medical Outcomes Study Short Form 12 (SF-12) was obtained for patients without Down syndrome when they were aged older than 15 years. RESULTS: Repair of PAVSD was done in 133 patients. Median follow-up was 8.7 years for a total of 1541 person-years. Mean age at the initial operation was 5.2 +/- 5.1 years (median, 3.4 years). Mean weight was 19.2 +/- 16.0 kg (median, 13.2 kg). Survival was 95% at 30 days, 87% at 10 years, and 78% at 30 years. Reoperation for left atrioventricular valve pathology was done 15 patients (11.3%). Lower weight, absence of Down syndrome, and lack of mitral valve cleft repair were significantly associated with undergoing reoperation. Patient-reported health status was obtained in 35 patients. For this group, the mean SF-12 summary scores for the physical component (52.8 +/- 9.0) and the mean mental component (50.3 +/- 11.0) were not significantly different from age-adjusted norms. CONCLUSIONS: The survival rate for this simple cardiac defect is lower than the general population. In addition, the reoperation rate is significant. Despite this, in general, patients without Down syndrome can expect normal functional health status.

Improving the quality of surveillance data on congenital heart defects in the metropolitan Atlanta congenital defects program.

BACKGROUND: One of the challenges in epidemiologic studies of congenital heart defects (CHDs) has been the lack of a current, standard nomenclature and classification system. Recently such a standard nomenclature became available from the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database. This study reports the classification of cases of CHDs in a birth defects surveillance database using modified STS nomenclature. METHODS: Records of infants and fetuses in the Metropolitan Atlanta Congenital Defects Program delivered during 1968-2003 with CHD diagnoses were reviewed by a team of pediatric cardiologists. The cases were assigned one or more STS codes and subsequently grouped into successively broader levels of aggregation. Aggregation was based on presumed morphogenetically similar developmental mechanisms. RESULTS: There were 12,639 cases reviewed, of which 89% had a single, primary STS code. Structural CHDs were found in 7,749 infants, while 4,890 were considered to have structurally normal hearts. Application of clinical CHD nomenclature improved the clinical accuracy of surveillance data by eliminating normal physiologic variants and obligatory shunt lesions. Classification also aggregated specific CHDs into groups appropriate for research and surveillance. CONCLUSIONS: Application of a current, standard CHD nomenclature and classification system to cases in a birth defects surveillance database improves the specificity of cardiac diagnoses and allows for the development of a flexible case aggregation system for monitoring of CHD prevalence.

Nitric oxide and fetal coronary regulation.

The determinants of coronary flow in the heart were studied using the chronic near-term fetal sheep model. Coronary flows were measured using implanted Doppler probes on the fetal circumflex artery calibrated with radiolabelled microspheres. Experiments were conducted to calculate maximal coronary flow under conditions of systolic work, chronic, and acute hypoxemia. Pressure-flow conductance curves were also constructed during adenosine administration. These studied showed that maximal right ventricular systolic work increases flow from a resting level of some 200 mL x min(-1) x 100 g(-1) to only about 60% of the maximal coronary flow under chemical vasodilation with adenosine (800 mL x min(-1) x 100 g(-1)). Chronic hypoxemia leads to a resting flow of some 800 mL x min(-1) x 100 g(-1) but with a remaining reserve of some 400 mL x min(-1) x 100 g(-1). Nitric oxide synthase blockade with N(ú)-nitro-L-arginine (L-NNA) depresses coronary flow at all levels of oxygen content and depresses myocardial oxygen consumption even under normoxemic conditions. Fetal coronary flow increases dramatically during severe acute hypoxemia and may exceed the maximal levels found during adenosine administration without a loss of ventricular function. However, in the presence of L-NNA and severe hypoxemia, coronary flow does not exceed flows found during adenosine administration.

Missense mutations in CRELD1 are associated with cardiac atrioventricular septal defects.

Atrioventricular septal defects (AVSD) are common cardiovascular malformations, occurring in 3.5/10,000 births. Although frequently associated with trisomy 21, autosomal dominant AVSD has also been described. Recently we identified and characterized the cell adhesion molecule CRELD1 (previously known as "cirrin") as a candidate gene for the AVSD2 locus mapping to chromosome 3p25. Analysis of the CRELD1 gene from individuals with non-trisomy 21-associated AVSD identified heterozygous missense mutations in nearly 6% of this population, including mutations in isolated AVSD and AVSD associated with heterotaxy syndrome. CRELD1 is the first human gene to be implicated in the pathogenesis of isolated AVSD and AVSD in the context of heterotaxy, which provides an important step in unraveling the pathogenesis of AVSD.