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ABSTRACT: OBJECTIVE: The purpose of this study was to evaluate the association between fetal development of congenital heart defects (CHD) and maternal prepregnancy body mass index (BMI, kg/m(2) ) in the largest population-based case-control study to date. BACKGROUND: Mounting evidence implicates maternal obesity as a risk factor for birth defects. However, the association between maternal obesity and CHD in offspring has been less completely described. METHODS: We conducted a study of CHD using linked birth-hospital discharge records for Washington State between 1992-2007. All infants with CHD (n = 14 142) were identified based on ICD9-CM discharge diagnosis codes. 141 420 controls, frequency matched on year of delivery, were selected at random from among infants without CHD. Maternal BMI was calculated from maternal prepregnancy data. Odds ratios (OR) and 95% confidence intervals (CI) for the association of CHD relative to maternal BMI were calculated, adjusted for gestational diabetes. RESULTS: Infants with CHD were more likely to have an obese mother (OR 1.22, 95% CI 1.15-1.30). The strength of association increased with increasing BMI (BMI 30-34.9: OR 1.16, 95% CI 1.07-1.25; BMI 35-39.9: OR 1.25, 95% CI 1.13-1.39; BMI > = 40: OR 1.49, 95% CI 1.32-1.69). The association was greatest for left and right ventricular outflow tract defects (OR 1.27, 95% CI 1.02-1.59 and OR 1.43, 95% CI 1.20-1.69, respectively). Hypoplastic left heart syndrome was markedly associated (OR 1.86, 95% CI 1.13-3.05). There was no association with conotruncal defects (OR 1.04, 95% CI: 0.82-1.33). CONCLUSIONS: We confirmed the association between CHD and maternal obesity and observed increasing risk with increasing obesity. Outflow tract defects appear uniquely associated. A greater risk of CHD among offspring is an important outcome of maternal obesity, and suggests a need for targeted medical management strategies.
Congenital Heart Disease 09/2012; · 0.90 Impact Factor
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ABSTRACT: To establish a classification of bicuspid aortic valve (BAV) that includes both leaflet morphology and aortic shape.
Two academic medical centres of the University of Washington, Seattle.
191 adult patients with BAV.
Review of clinical data and transthoracic echocardiograms.
Assessment of leaflet morphology; valve function; aortic shape and dimensions.
We identified three morphologies: type 1, fusion of right and left coronary cusp (n = 152); type 2, right and non-coronary fusion (n = 39); and type 3, left and non-coronary fusion (n = 1). Comparing type 1 and 2 BAV, there were no significant differences in age, height, weight, blood pressure or aortic valve function. Type 1 was more common in men (69 vs 45%). The aortic sinuses were larger in type 1, while type 2 had larger arch dimensions. Myxomatous mitral valves were more common in type 2 BAV (13% vs 2.6%, p<0.05). Three aortic shapes were defined: normal (N), sinus effacement (E), and ascending dilatation (A). Comparing type 1 to type 2 BAV, shape N was more common in type 1 (60% vs 32%), and type A was more common in type 2 (35% vs 54%,); type E was rare (p<0.01 across all groups).
A comprehensive BAV phenotype includes aortic shape. Type 1 BAV is associated with male gender and normal aortic shape but a larger sinus diameter. Type 2 leaflet morphology is associated with ascending aorta dilatation , larger arch dimensions and higher prevalence of myxomatous mitral valve disease.
Heart (British Cardiac Society) 02/2008; 94(12):1634-8. · 4.22 Impact Factor
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ABSTRACT: Bicuspid aortic valve (BAV) affects about 0.5% to 2% of the population and predisposes patients to aortic dilation and dissection. We hypothesized that aortic size and elastic properties are related to BAV phenotype. In a retrospective study of 158 consecutive patients with BAV referred for echocardiography, the phenotype was defined as anterior-posterior (A-P) leaflet orientation or right-left (R-L) leaflet orientation. The 29 subjects with R-L BAV were matched 1:1 for age, gender, and grade of aortic valve dysfunction with 29 subjects with A-P BAV. Aortic dimensions were measured at the sinuses of Valsalva, ascending aorta, and aortic arch. Distensibility and stiffness index were calculated using cuff blood pressure. Mean age was 41.5 years (range 21 to 67), and 59% were men. Aortic diameter was larger with A-P BAV than R-L at the sinuses (mean +/- 1 SD 3.48 +/- 0.49 vs 3.06 +/- 0.59, p <0 .01) and smaller at the arch (2.34 +/- 0.40 vs 2.83 +/- 0.45, p <0.001). At the sinuses, A-P BAV had a higher stiffness index (median 12.98, range 2.78 to 42.07 vs 6.41, range 2.75 to 59.72, p <0.01) and lower distensibility. Stiffness index in the ascending aorta and arch (but not at the sinus) increased with age. In conclusion, A-P BAV is associated with a larger stiffer sinus of Valsalva and smaller arch diameter. The potential impact of BAV phenotype and aortic elasticity on clinical outcomes merits further study.
The American Journal of Cardiology 03/2007; 99(5):686-90. · 3.37 Impact Factor
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Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital 02/2006; 33(3):404-5. · 0.65 Impact Factor
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Circulation 03/2005; 111(7):832-4. · 14.74 Impact Factor
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Mark B Lewin,
Kim L McBride,
Ricardo Pignatelli,
Susan Fernbach,
Ana Combes,
Andres Menesses,
Wilbur Lam,
Louis I Bezold,
Norman Kaplan,
Jeffrey A Towbin,
John W Belmont
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ABSTRACT: Left ventricular outflow tract obstructive (LVOTO) malformations are a leading cause of infant mortality from birth defects. Genetic mechanisms are likely, and there may be a higher rate of asymptomatic LVOTO anomalies in relatives of affected children. This study sought to define the incidence of cardiac anomalies in first-degree relatives of children with congenital aortic valve stenosis (AVS), coarctation of the aorta (CoA), and hypoplastic left heart syndrome (HLHS).
A total of 113 probands with a nonsyndromic LVOTO malformation of AVS (n = 25), BAV (n = 3), CoA (n = 52), HLHS (n = 30), and aortic hypoplasia with mitral valve atresia (n = 2) were ascertained through chart review or enrolled at the time of diagnosis. Echocardiography was performed on 282 asymptomatic first-degree relatives.
Four studies had poor acoustic windows, leaving 278 studies for analysis. BAV were found in 13 (4.68%) first-degree relatives. The relative risk of BAV in the relatives was 5.05 (95% confidence interval: 2.2-11.7), and the broad sense heritability was 0.49, based on a general population frequency of 0.9%. BAV was more common in multiplex families compared with sporadic cases. An additional 32 relatives had anomalies of the aorta, aortic valve, left ventricle, or mitral valve.
The presence of an LVOTO lesion greatly increases the risk of identifying BAV in a parent or sibling, providing additional support for a complex genetic cause. The parents and siblings of affected patients should be screened by echocardiography as the presence of an asymptomatic BAV may carry a significant long-term health risk.
PEDIATRICS 10/2004; 114(3):691-6. · 4.47 Impact Factor
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ABSTRACT: The understanding of the etiology of congenital cardiac lesions is rapidly progressing from the recognition of embryologic origins to insight into the genetic basis for these disorders. Concurrently, in this era, great effort is being expended to gather data that will generate clinically useful genotype-phenotype correlation. This rapidly evolving area of inquiry, in which the clinical implications of mutation status are fully explored, makes available information applicable to those involved in all aspects of congenital cardiac disease.
Three syndromes with cardiovascular phenotypes were selected for review. Each has received a great deal of attention in the recent past based on improved understanding of the range of mutations expressed and the relation of these mutations to clinical findings. These three syndromes--Noonan, Marfan, and long QT syndrome--span the range of congenital heart disease and provide examples of genotype-phenotype correlation.
Better understanding of the clinical implications of specific mutations should allow not only for more sensitive and specific diagnoses to be made but also for improvements in therapeutic options and efficacy.
Current Opinion in Cardiology 06/2004; 19(3):221-7. · 2.33 Impact Factor
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Journal of the American Society of Echocardiography 04/2004; 17(3):284-5. · 3.71 Impact Factor
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ABSTRACT: The cardiovascular effects of volatile anesthetics in children with congenital heart disease have been studied, but there are limited data on the effects of anesthetics on pulmonary-to-systemic blood flow ratio (Qp:Qs) in patients with intracardiac shunting. In this study, we compared the effects of halothane, isoflurane, sevoflurane, and fentanyl/midazolam on Qp:Qs and myocardial contractility in patients with atrial (ASD) or ventricular (VSD) septal defects. Forty patients younger than 14 yr old scheduled to undergo repair of ASD or VSD were randomized to receive halothane, sevoflurane, isoflurane, or fentanyl/midazolam. Cardiovascular and echocardiographic data were recorded at baseline, randomly ordered 1 and 1.5 mean alveolar anesthetic concentration (MAC) levels, or predicted equivalent fentanyl/midazolam plasma levels. Ejection fraction (using the modified Simpson's rule) was calculated. Systemic (Qs) and pulmonary (Qp) blood flow was echocardiographically assessed by the velocity-time integral method. Qp:Qs was not significantly affected by any of the four regimens at either anesthetic level. Left ventricular systolic function was mildly depressed by isoflurane and sevoflurane at 1.5 MAC and depressed by halothane at 1 and 1.5 MAC. Sevoflurane, halothane, isoflurane, or fentanyl/midazolam in 1 or 1.5 MAC concentrations or their equivalent do not change Qp:Qs in patients with isolated ASD or VSD. IMPLICATIONS: Sevoflurane, halothane, isoflurane, and fentanyl/midazolam do not change pulmonary-to-systemic blood flow ratio in children with atrial and ventricular septal defects when administered at standard anesthetic doses with 100% oxygen.
Anesthesia & Analgesia 12/2002; 95(5):1200-6, table of contents. · 3.29 Impact Factor
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ABSTRACT: Molecular analysis of the gene encoding the protein tyrosine phospatase, nonreceptor type 11 (PTPN11), identified a single base change at nucleotide 228 in an individual manifesting Noonan syndrome with aortic root widening and dysplastic aortic and mitral valves. This missense mutation changes glutamate to aspartate at position 76 of the protein (E76D or Glu76Asp), which likely disrupts intramolecular hydrogen bonding of this protein. There are few reports of aortic root dilatation in Noonan syndrome, and to our knowledge this is the first case with a confirmed PTPN11 mutation.
Pediatric Cardiology 27(4):478-80. · 1.30 Impact Factor
