Thrombus formation in the native aortic root in patients with hypoplastic left heart syndrome.

Thrombus formation in the native aortic root is a rare but potentially life-threatening complication in patients with hypoplastic left heart syndrome. The native aortic root in these patients serves as a conduit for the retrograde filling of the coronary arteries. Thrombus in this location could result in myocardial ischemia. We present three cases of native aortic root thrombosis at our institution with clinical presentations ranging from asymptomatic to sudden cardiac arrest. Our experience with these patients argues for careful and consistent evaluation of the native aortic root regardless of clinical symptoms.

99mTc-SnF2 colloid "LLK": particle size, morphology and leucocyte labelling behaviour.

99mTc-SnF2 colloid (Radpharm LLK) leucocyte labelling agent is used in whole blood, exploiting phagocytosis. The objectives of this work were to optimize leucocyte labelling in leucocyte-enriched plasma, and to investigate: (i) the effect of temperature and other factors on labelling efficiency; (ii) the selectivity for different leucocyte types; (iii) the viability of the labelled cells and efflux of the radiolabel; and (iv) the physical characteristics of the colloid. Density gradient centrifugation was used to investigate the labelling efficiency, cell selectivity and efflux, Trypan blue to study the viability, and laser scattering, electron microscopy and membrane filtration to investigate particle size and morphology. Particles appeared as loose, coiled, chain-like aggregates of much smaller particles (<0.05 microm). The aggregate diameter ranged from <0.1 to >5 microm and increased with time. The distribution of radioactivity amongst the particle sizes varied widely. The labelling efficiency in leucocyte-rich plasma was enhanced at 37 degrees C compared to room temperature, and by centrifuging during labelling. The selectivity for different leucocyte types varied markedly between batches and blood samples, in some cases showing preference for mononuclear cells and in others for granulocytes. Viability was excellent and comparable with 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO)-labelled cells. A significant fraction of radiolabel, comparable to that observed with 99mTc-HMPAO, was lost from leucocytes during incubation in vitro over 4 h. Thus, 99mTc-SnF2 is a convenient, efficient labelling agent for leucocytes, but shows variable cell selectivity which may be linked to particle size variability, and there is significant efflux of radioactivity from labelled cells.

The influence of a restrictive atrial septal defect on pulmonary vascular morphology in patients with hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) with a restrictive atrial septal defect (ASD) is a form of congenital heart disease with considerable morbidity and mortality. This morphologic analysis assesses the pulmonary vasculature in this patient population. Pulmonary arteries, the persistence of high-resistance fetal arterioles, pulmonary veins, and lymphatics from multiple lung sections from each of five patients with HLHS and a restrictive ASD were compared to those of five patients with HLHS and nonrestrictive ASD. Lung sections from each patient were qualitatively graded in severity of pathology from 0 to 3 for each of the structures described previously, with the pathologist blinded to the status of the ASD. Patients with a restrictive ASD exhibited more significant pulmonary venous thickening and lymphatic dilatation (p = 0.02), with a tendency toward persistence of high-resistance fetal vessels (p = 0.2), compared to patients with a nonrestrictive ASD. These findings imply that patients with HLHS and a restrictive ASD possess pulmonary vascular abnormalities that place them at higher risk for the current surgical interventions available compared to patients with a nonrestrictive ASD.

Use of peak Doppler gradient across ventricular septal defects leads to underestimation of right-sided pressures in patients with "sloped" Doppler signals.

In patients with "sloped" appearance of the Doppler signal across a ventricular septal defect (VSD), the peak Doppler velocity seems to overestimate the catheterization-derived peak-to-peak gradient, resulting in underestimation of right-sided heart pressures. In 11 patients with sloped Doppler signals across the VSD, ventricular pressure tracings were compared with simultaneous recordings of the Doppler signal. The average peak Doppler gradient (40.2 +/- 19.2 mm Hg) overestimated the catheterization-derived peak-to-peak gradient (20.2 +/- 13.6 mm Hg) significantly (P < or =.001). Doppler mean gradient (20.2 +/- 11.3 mm Hg; P = ns) and end-systolic gradient (17.0 +/- 12.5 mm Hg; P < or =.05) were closer estimates of the catheterization peak-to-peak gradient. All Doppler gradients showed good correlation to the catheterization peak-to-peak gradient with r2 values of 0.77, 0.73, and 0.91. We conclude that Doppler mean or end-systolic gradients should be used for calculation of right-sided heart pressures in this patient population.

Energy expenditure after surgical repair in children with cyanotic congenital heart disease.

OBJECTIVE: Infants with cyanotic congenital heart disease (CCHD) have previously been shown to have similar resting energy expenditures (REEs) and elevated total energy expenditures (TEEs) compared with age-matched healthy infants. The purpose of this investigation was to re-examine the REE and TEE of the same individuals at 5 years of age, after surgical repair of the heart defect was done, to determine whether metabolic differences persist. STUDY DESIGN: Seven children were studied approximately 2.6 years after they underwent surgical repair of CCHD along with 10 age-matched healthy children. Indirect calorimetry was used to determine REE, and the doubly labeled water method was used to determine TEE and body composition. RESULTS: Results were compared with single-factor repeated measures analysis of variance. No significant differences were found between groups in weight or body composition. No significant differences were found between groups in REE, TEE, or the energy expended in physical activity. CONCLUSION: We conclude that differences in TEE observed during infancy are no longer present in 5-year-old children after they undergo surgical repair of CCHD. Furthermore, the individual components of energy expenditure of children with CCHD after repair are indistinguishable from those of healthy age-matched children.

Increased energy expenditure in infants with cyanotic congenital heart disease.

Infants with cyanotic congenital heart disease (CCHD) often have reduced weight gain compared with infants in control groups. Our purpose was to conduct a longitudinal study of energy intake, resting energy expenditure (REE), and total energy expenditure (TEE) of a group of infants with CCHD. We hypothesized that increased REE and TEE and decreased energy intake in these infants would lead to reduced growth. Ten infants with uncorrected CCHD and 12 infants in a control group were studied at 2 weeks of age and again at 3 months. Indirect calorimetry was used to determine REE; the doubly labeled water method was used to determine TEE and intake. At 2 weeks and 3 months of age, infants with CCHD weighed significantly less than infants in the control group. No significant difference was seen in energy intake or REE between groups during either period. TEE was slightly but not statistically increased in the CCHD group at 2 weeks (72.6 +/- 17.4 vs 59.8 +/- 10.9 kcal/kg/d) and significantly increased at 3 months (93.6 +/- 23.3 vs 72.2 +/- 13.2 kcal/kg/d, P

Total but not resting energy expenditure is increased in infants with ventricular septal defects.

OBJECTIVE: The purpose of this study was to determine the effect of left-to-right shunting on the resting energy expenditure (REE), total energy expenditure (TEE), and energy intake in a group of 3- to 5-month-old infants with moderate to large unrepaired ventricular septal defects (VSDs) compared with age-matched, healthy infants. METHODS: Eight infants with VSDs and 10 healthy controls between 3 to 5 months of age participated in the study. Indirect calorimetry was used to measure REE and the doubly-labeled water method was used to measure TEE and energy intake. An echocardiogram and anthropometric measurements were performed on all study participants. Daily urine samples were collected at home for 7 days. Samples were analyzed by isotope ratio mass spectrometry. Data were compared using analysis of variance. RESULTS: No significant differences were found in REE (VSD, 42.2 +/- 8.7 kcal/kg/d; control, 43.9 +/- 14.1 kcal/kg/d) or energy intake (VSD, 90.8 +/- 19.9 kcal/kg/d; control, 87.1 +/- 11.7 kcal/kg/d) between the groups. The percent total body water was significantly higher in the VSD infants and the percent fat mass was significantly lower. TEE was 40% higher in the VSD group (VSD, 87.6 +/- 10.8 kcal/kg/d; control, 61.9 +/- 10.3 kcal/kg/d). The difference between TEE and REE, reflecting the energy of activity, was 2.5 times greater in the VSD group. CONCLUSIONS: REE and energy intake are virtually identical between the two groups. Despite this, infants with VSDs have substantially higher TEE than age-matched healthy infants. The large difference between TEE and REE in VSD infants suggests a substantially elevated energy cost of physical activity in these infants. These results demonstrate that, although infants with VSDs may match the energy intake of healthy infants, they are unable to meet their increased energy demands, resulting in growth retardation.

Dilutional and modified ultrafiltration reduces pulmonary hypertension after operations for congenital heart disease: a prospective randomized study.

OBJECTIVE: A prospective randomized study was performed to test whether removal of endothelin-1, by ultrafiltration techniques, will reduce pulmonary hypertension after operations for congenital heart disease. METHODS: Twenty-four patients with pulmonary hypertension (systolic pulmonary/systemic arterial pressure ratio > 60%) undergoing cardiac operations were randomized into a control group (n = 12) having conventional ultrafiltration and an experimental group (n = 12) undergoing dilutional ultrafiltration during and modified ultrafiltration after cardiopulmonary bypass. Plasma endothelin-1, nitric oxide metabolites, and cyclic guanosine monophosphate were assayed before bypass, 10 minutes into bypass, after bypass, and 0, 3, 6, and 12 hours after the operation in both groups, as well as in the ultrafiltrates and after modified ultrafiltration in the experimental group. Both groups received alpha-blockers (chlorpromazine and/or prazosin) postoperatively using the same guidelines. RESULTS: The ultrafiltrates contained significant amounts of endothelin-1 (1.81 +/- 0.86 pg/ml, dilutional, and 6.44 +/- 1.82 pg/ml, modified ultrafiltrate). Endothelin-1 and the pulmonary/systemic pressure ratio were significantly lower in experimental compared with control patients. Nitric oxide metabolites and cyclic guanosine monophosphate increased similarly in both groups for 12 hours after the operation (p = not significant). Three of 12 control patients (25%) but no experimental patients had pulmonary hypertensive crises (p = 0.07). The experimental patients required significantly less ventilatory support (67 +/- 47 hours vs 178 +/- 139 hours for control patients, p = 0.048). CONCLUSIONS: Dilutional and modified ultrafiltration reduce endothelin-1 and the pulmonary/systemic pressure ratio postoperatively and may become an important adjunct for preventing pulmonary hypertension after operations for congenital heart disease in high-risk patients.

Dynamic changes of endothelin-1, nitric oxide, and cyclic GMP in patients with congenital heart disease.

BACKGROUND: Pulmonary hypertension causes major morbidity and mortality after congenital heart surgery, but its mechanism remains unclear. METHODS AND RESULTS: Plasma endothelin-1 (ET-1), nitric oxide (NO), and cyclic GMP (cGMP) were assayed at 6 intervals in 50 children undergoing cardiopulmonary bypass (CPB): before CPB, 10 minutes into CPB, and 0, 3, 6, and 12 hours after CPB. Three groups based on pulmonary flow and pressure were analyzed: low flow (LF, n=21), high flow/low pressure (systolic pulmonary pressure/systemic pressure ratio, Pp/Ps<50%, HF-LP, n=11), and high flow/high pressure (Pp/Ps> or =50%, HF-HP, n=19). HF-HP and HF-LP received alpha-blockers (chlorpromazine and/or prazosin). HF-HP patients received nitric oxide donors (nitroglycerin/sodium nitroprusside). ET-1 peaked at 6 hours, with its highest level in the HF-HP group (P<.01, by ANOVA). ET-1 correlated significantly with Pp/Ps at 6 hours (r2=.43, P<.005). In the HF-HP group, ET-1 remained above the other groups at 12 hours (12.7+/-2.5 pg/mL versus 6.4+/-1.1 pg/mL versus 6.5+/-3.8 pg/mL P<.05 by ANOVA). NO metabolites were elevated equivalently for the HF-HP and HF-LP groups (5.7+/-2.6 micromol/L versus 0.3.5+/-2.5 micromol/L at 12 hours, P=NS) despite nitric oxide donors and the excess ET-1 in HF-HP patients. Levels of cGMP were similarly elevated in HF-HP and HF-LP patients during this study. CONCLUSIONS: Endogenous NO may decrease vascular tone and maintain low pulmonary pressure in HF-LP patients. High levels of ET-1, inadequate NO production, and/or impaired responses to NO may increase pulmonary pressure in HF-HP patients.

Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis.

Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.

Dynamic three-dimensional echocardiographic reconstruction of congenital cardiac septation defects.

Dynamic three-dimensional echocardiographic reconstructions of 27 cardiac septation defects were performed in 19 sedated infants and children. Using a subxiphoid rotational scanning approach, complete visualization of the entire shape and breadth of the defect was attained in 11 of 16 ventricular septal defects and 9 of 11 atrial septal defects. This technique enabled the operator to cut slices from the three-dimensional block of echocardiographic data in order to present septation defects in a region- or lesion-oriented fashion. Poor baseline two-dimensional image quality and certain small septation defects that were readily obscured by nearby structures led to inadequate three-dimensional reconstructions. The application of dynamic three-dimensional echocardiography for assessment of cardiac septation defects uniquely provided (1) the ability to present en face views of atrial and ventricular septal defects; and (2) a means by which intracardiac anatomy can be displayed in a region- and lesion-oriented fashion for interventional and surgical planning purposes.

Biodistribution of 123I-labeled 4-hydroxytamoxifen derivatives in rats with dimethylbenzanthracene-induced mammary carcinomas.

A 123I-labeled tamoxifen derivative with a high affinity for the antiestrogen-binding site (AEBS) has been prepared. Biodistribution studies in rats showed a good linear correlation between the AEBS contents of tissue in fmol/g and the accumulated amount of radioactivity in percent dose per gram at 24 h.

Doppler derivation of complete pulmonary artery pressure curves in patent ductus arteriosus.

Doppler echocardiography can be used in patients with a patent ductus arteriosus to generate complete pulmonary artery pressure curves. This technique provides a dynamic evaluation of changes in pulmonary artery pressures throughout the cardiac cycle and provides more hemodynamic information than single-point Doppler velocity methods of estimating pulmonary artery pressures.

Surgical management of total anomalous pulmonary venous connection. Thirty-year trends.

BACKGROUND: Reports of surgical correction of total anomalous pulmonary venous connection (TAPVC) over the past 30 years indicate a general improvement in operative survival. However, prevention of late pulmonary venous obstruction continues to be a cornerstone of successful repair. The purpose of the study was to identify factors associated with improvement in perioperative mortality and to determine risk factors for death and reoperation due to pulmonary vein stenosis after repair of TAPVC. METHODS AND RESULTS: Using univariate and multiple regression analysis, we analyzed risk of early and late mortality and need for reoperation in 105 patients operated on between April 1966 and June 1995. Despite increased frequency of neonatal repair in the most recent time period (29% in 1966 through 1985; 55% in 1991 through 1995, P < .05), operative mortality declined (13% in 1966 through 1985; 0% in 1991 through 1995). The incidence of postoperative pulmonary hypertensive episodes and death related to pulmonary hypertension decreased significantly over the study period (P < .001). Aggressive preoperative elective medical stabilization and prophylaxis of postoperative pulmonary hypertensive episodes may have contributed to this improvement. By univariate analysis, preoperative pulmonary hypertension (P < .02) and preoperative pulmonary vein obstruction (P < .01) correlated with early mortality up to 1990 but not in the past 5 years. Multiple logistic regression analysis showed that only a small pulmonary confluence associated with diffuse pulmonary vein stenosis was an independent risk factor for early (P < .001) and late (P = .01) death as well as need for reoperation (P = .007). Type of TAPVC was not a significant risk factor throughout the three decades of our experience. At a median follow-up of 87 months, late survival was 98% (93 of 95 operative survivors), and all are NYHA class I. CONCLUSIONS: Improvements on surgical technique as well as preoperative and postoperative management account for the reduction in mortality and need for reoperation for most types of TAPVC. However, the presence of a small venous confluence and diffuse pulmonary vein stenosis remains a risk factor for adverse outcome.

LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition.

To identify genes important for human cognitive development, we studied Williams syndrome (WS), a developmental disorder that includes poor visuospatial constructive cognition. Here we describe two families with a partial WS phenotype; affected members have the specific WS cognitive profile and vascular disease, but lack other WS features. Submicroscopic chromosome 7q11.23 deletions cosegregate with this phenotype in both families. DNA sequence analyses of the region affected by the smallest deletion (83.6 kb) revealed two genes, elastin (ELN) and LIM-kinase1 (LIMK1). The latter encodes a novel protein kinase with LIM domains and is strongly expressed in the brain. Because ELN mutations cause vascular disease but not cognitive abnormalities, these data implicate LIMK1 hemizygosity in imparied visuospatial constructive cognition.

Surgical management of hypoplastic left heart syndrome.

BACKGROUND: The treatment of infants with hypoplastic left heart syndrome has been challenging and controversial. METHODS: To assess the operative management and intermediate-term outcome, we retrospectively analyzed our surgical experience with 50 newborns with hypoplastic left heart syndrome operated on between January 1989 and June 1995. RESULTS: Surgical palliation with a first-stage Norwood operation was offered to 28 patients. The remaining 22 infants were initially listed for heart transplantation, and 15 underwent the operation. Ten of the 15 recipients are alive, and all are in New York Heart Association class I. Seven infants underwent a Norwood procedure after being on the list for transplantation for 12 to 42 days. A total of 34 patients underwent Norwood procedures with one operation aborted because of inoperable anatomy. Two infants who survived the first-stage Norwood operation underwent subsequent heart transplantation and are currently doing well. The 1-year mortality rate for heart transplantation was 18% (3/17) versus 50% (17/34) for the Norwood procedure. Risk factors for early mortality after a Norwood procedure include longer circulatory arrest time (> 50 minutes), preoperative acidosis (pH < 7.20), larger systemic-pulmonary artery shunt (> or = 4 mm), diminutive ascending aorta (< or = 2.0 mm), and anatomic subtype of aortic and mitral atresia. The 1-year survival rate for the Norwood procedure improved from 36% for the patients operated on during 1989 through 1992 to 75% during 1993 to mid-1995 (p = 0.005). Of the 17 survivors of a first-stage Norwood operation, 10 have undergone the second stage (bidirectional Glenn procedure), and 7 have completed a Fontan procedure. Heart transplantation results have also improved, with no deaths since 1992. CONCLUSIONS: Both the Norwood procedure and heart transplantation have encouraging early to intermediate results in infants with hypoplastic left heart syndrome. Hypoplastic left heart syndrome should be managed selectively on the basis of cardiac morphology, donor availability, and family wishes. Development of a flexible program involving the use of both procedures may aid in the successful management of infants with hypoplastic left heart syndrome.

Ventricular septal aneurysm after atrioventricular septal repair with pericardium.

A 2-month-old infant underwent a two-patch repair of a type C atrioventricular septal defect using autologous pericardium. Several months later a large, symptomatic aneurysm of the ventricular septal patch developed, requiring resection. The use of untreated autologous pericardium for large, congenital ventricular septal defects is unpredictable and should be avoided.

A systematic approach to echocardiographic image acquisition and three-dimensional reconstruction with a subxiphoid rotational scan.

Rotational scanning from the subxiphoid position is an image acquisition technique used for reconstruction of dynamic three-dimensional echocardiographic images in infants and small children. The orientation of the heart within the three-dimensional data set is variable and dependent on the image plane at which rotational scanning was initiated. We describe an image acquisition technique that standardizes the orientation of the heart within the three-dimensional data set, thereby permitting a systematic approach to the reconstruction of three-dimensional renderings. Thirteen infants and small children with congenital heart disease were studied by this approach. Illustrative examples are provided. The average time required to derive a three-dimensional rendering was 37 +/- 9 minutes. We conclude that subxiphoid rotational scanning by a systematic approach to image acquisition and reconstruction can be applied successfully to the derivation of three-dimensional renderings of congenital cardiac defects.

Surgical management of complete atrioventricular septal defects. A twenty-year experience.

Creation of a competent left atrioventricular valve is a cornerstone in surgical repair of complete atrioventricular septal defects. To identify risk factors for mortality and failure of left atrioventricular valve repair and to determine the impact of cleft closure on postoperative atrioventricular valve function, we retrospectively analyzed hospital records of 203 patients between January 1974 and January 1995. Overall early mortality was 7.9%. Operative mortality decreased significantly over the period of the study from 19% (4/21) before 1980 to 3% (2/67) after 1990 (p = 0.03). Ten-year survival including operative mortality was 91.3% +/- 0.004% (95% confidence limit): all survivors are in New York Heart Association class I or II. Preoperative atrioventricular valve regurgitation was assessed in 203 patients by angiography or echocardiography and was trivial or mild in 103 (52%), moderate in 82 (41%), and severe in 18 (8%). Left atrioventricular valve cleft was closed in 93% (189/203) but left alone when valve leaflet tissue was inadequate and closure of the cleft might cause significant stenosis. Reoperation for severe postoperative left atrioventricular valve regurgitation was necessary in eight patients, five of whom initially did not have closure of the cleft and three of whom had cleft closure. Six patients had reoperation with annuloplasty and two patients required left atrioventricular valve replacement. Five patients survived reoperation and are currently in New York Heart Association class I or II. On most recent evaluation assessed by angiography or echocardiography (a mean of 59 months after repair), left atrioventricular valve regurgitation was trivial or mild in 137 of the 146 survivors (94%) examined; none had moderate or severe left atrioventricular valve stenosis. By multiple logistic regression analysis, strong risk factors for early death and need for reoperation included postoperative pulmonary hypertensive crisis, immediate postoperative severe left atrioventricular valve regurgitation, and double-orifice left atrioventricular valve. These results indicate that complete atrioventricular septal defects can be repaired with low mortality and good intermediate to long-term results. Routine approximation of the cleft is safe and has a low incidence of reoperation for left atrioventricular valve regurgitation.