Evaluation of systolic and diastolic ventricular performance of the right ventricle in fetuses with ductal constriction using the Doppler Tei index.

Fetal ductal constriction (DC) can depress right ventricular (RV) function. However, noninvasive assessment of fetal RV function remains difficult. We evaluated RV and left ventricular (LV) performance in fetuses with DC using the Doppler-derived Tei index. The Tei index measures the ratio of total time spent in isovolumic contraction and relaxation (isovolumic time) to the ejection time. Tricuspid inflow and RV outflow Doppler traces for the derivation of RV Tei indexes and mitral inflow and LV outflow traces for LV Tei indexes were measured in 78 fetuses of pregnant women who received indomethacin and 70 normal fetuses (gestational ages ranging from 20 to 39 weeks). DC occurred in 23 fetuses, defined as pulsatility index <1.9. In fetuses with DC, the RV isovolumic time was prolonged and RV ejection time was shortened, and the RV Tei index was high compared with those in fetuses that received indomethacin without DC and normal fetuses. Also, the RV Tei index clearly separated the fetuses with DC from normal and fetuses that received indomethacin without DC (0.74 +/- 0.14 vs 0.35 +/- 0.07 and 0.37 +/- 0.06, respectively; p <0.0001). The LV Tei index was not affected by DC. Serial study in 7 fetuses with DC showed that the RV Tei index decreased from 0.69 +/- 0.12 to 0.38 +/- 0.04 (p = 0.0002) after discontinuation of indomethacin coincident with ductal relaxation, although it remained elevated in 2 cases at the time of ductal relaxation. Thus, the Tei index is a useful and sensitive indicator for detecting abnormal RV performance in fetuses with DC.

Congenital heart disease: current indications for antithrombotic therapy in pediatric patients.

This report reviews the current status of antithrombotic therapy, including anti-platelet therapy, in pediatric patients with congenital heart disease. The current medications utilized and dose recommendations are emphasized, and indications for their use are reviewed.

Right ventricular systolic pressure load alters myocyte maturation in fetal sheep.

The effects of right ventricular (RV) systolic pressure (RVSP) load on fetal myocyte size and maturation were studied. Pulmonary artery (PA) pressure was increased by PA occlusion from mean 47.4 +/- 5.0 (+/-SD) to 71 +/- 13.6 mmHg (P < 0.0001) in eight RVSP-loaded near-term fetal sheep for 10 days. The maximal pressure generated by the RV with acute PA occlusion increased after RVSP load: 78 +/- 7 to 101 +/- 15 mmHg (P < 0.005). RVSP-load hearts were heavier (44.7 +/- 8.4 g) than five nonloaded hearts (31.8 +/- 0.2 g; P < 0.03); heart-to-body weight ratio (10.9 +/- 1.1 and 6.5 +/- 0.9 g/kg, respectively; P < 0.0001). RVSP-RV myocytes were longer (101.3 +/- 10.2 microm) than nonloaded RV myocytes (88.2 +/- 8.1 microm; P < 0. 02) and were more often binucleated (82 +/- 13%) than nonloaded myocytes (63 +/- 7%; P < 0.02). RVSP-loaded myocytes had less myofibrillar volume than did nonloaded hearts (44.1 +/- 4.4% and 56. 1 +/- 2.6%; P < 0.002). We conclude that RV systolic load 1) leads to RV myocyte enlargement, 2) has minor effects on left ventricular myocyte size, and 3) stimulates maturation (increased RV myocyte binucleation). Myocyte volume data suggest that RV systolic loading stimulates both hyperplastic and hypertrophic growth.

Coronary flow regulation in the fetal sheep.

The two ventricles of the fetal sheep heart have anatomic and biochemical differences that account for their differing functional capabilities and blood flows. Coronary flows to both ventricles have been measured using radiolabeled microspheres [or left ventricular (LV) flow, by Doppler sensor on the circumflex coronary artery] during experiments of pressure loading and chronic and acute hypoxemia. Blood flow to the left ventricle with its lower wall tension is about two-thirds the flow per gram compared with the right ventricle (RV). Acute systolic pressure loading of the RV to its maximal work capability stimulates flow to double (from approximately 250 to 500 ml. min(-1). 100 g(-1)), but to a level less than stimulated by adenosine (750 ml. min(-1). 100 g(-1)). At all RV work loads, LV flow remains at two-thirds RV flow. Resting myocardial flow levels in fetuses that have been chronically hypoxemic are similar to maximal adenosine-stimulated flows of normal fetal sheep. This flow augmentation is evidently due to vascular remodeling because a normal "flow reserve" of approximately 500 ml. min(-1). 100 g(-1) during adenosine administration remains. Acute hypoxemia stimulates myocardial flow to extraordinary levels (>1.5 l. min(-1). 100 g(-1)), levels larger than can be obtained with chemical dilation alone. LV flows do not exceed adenosine-stimulated flows when nitric oxide synthase is antagonized. We conclude 1) fetal RV coronary flow increases with RV work but to levels less than during adenosine stimulation; 2) the fetal heart is designed to accommodate extremely high flows in response to acute hypoxemia, partially through large production of nitric oxide; and 3) the fetal coronary tree is dramatically remodeled in response to chronic hypoxemia.

Is Down syndrome a risk factor for poor outcome after repair of congenital heart defects?

Down syndrome is commonly associated with significant congenital heart disease with the potential for early development of pulmonary hypertension. As such, children with Down syndrome may be at increased risk for both perioperative and long-term mortality. The purpose of this study, using data collected from a population-based outcomes study, is to analyze the potential role that Down syndrome plays in the outcome of surgically "corrected" congenital heart disease. Data were collected from a registry of all Oregon residents who, in the period 1958 to the present, had a reparative operation for one of 14 congenital cardiac malformations when younger than 18 years (N = 3965 patients). Down syndrome was present in 289 (7%) of the total registry patients. In evaluating the cardiac mortality associated with Down syndrome for each of the repaired cardiac malformations, only complete atrioventricular septal defect was associated with significantly higher perioperative (13% vs 5%) as well as higher overall late cardiac mortality through 20 years after the operation (20% vs 5%; p = 0.04). The survival outcomes for each of the other cardiac malformations were similar for children with and without Down syndrome.

Thirty-year incidence of infective endocarditis after surgery for congenital heart defect.

CONTEXT: The incidence of infective endocarditis after surgical repair of congenital heart defects is unknown. OBJECTIVE: To determine the long-term incidence of endocarditis after repair of any of 12 congenital heart defects in childhood. DESIGN: Population-based registry started in 1982. SETTING: State of Oregon. PARTICIPANTS: All Oregon residents who underwent surgical repair for 1 of 12 major congenital defects at the age of 18 years or younger from 1958 to the present. MAIN OUTCOME MEASURE: Diagnosis of infective endocarditis confirmed by hospital or autopsy records. RESULTS: Follow-up data were obtained from 88% of this cohort of 3860 individuals through 1993. At 25 years after surgery, the cumulative incidence of infective endocarditis was 1.3% for tetralogy of Fallot, 2.7% for isolated ventricular septal defect, 3.5% for coarctation of the aorta, 13.3% for valvular aortic stenosis, and 2.8% for primum atrial septal defect. In the cohorts with shorter follow-up, at 20 years after surgery the cumulative incidence was 4.0% for dextrotransposition of the great arteries; at 10 years, the cumulative incidence was 1.1% for complete atrioventricular septal defect, 5.3% for pulmonary atresia with an intact ventricular septum, and 6.4% for pulmonary atresia with ventricular septal defect. No children with secundum atrial septal defect, patent ductus arteriosus, or pulmonic stenosis have had infective endocarditis after surgery. CONCLUSION: The continuing incidence of endocarditis after surgery for congenital heart defect, particularly valvular aortic stenosis, merits education about endocarditis prophylaxis for children and adults with repaired congenital heart defects.

Two-dimensional echocardiographic evaluation of ventricular systolic function in human fetuses with ductal constriction.

Ventricular systolic function was assessed in fetuses, 18 with and 18 without constriction of the ductus arteriosus by serial two-dimensional and Doppler echocardiographic studies. Ductal constriction was defined as maximum systolic velocity of > 140 cm/s and diastolic flow velocity of > 30 cm/s. Ventricular end-diastolic and end-systolic areas were measured from a four-chamber view and area shortening fraction (SF) was calculated: area SF = (area in end-diastole--area in end-systole)/area in end-diastole. In fetuses with ductal constriction, right ventricular end-diastolic and end-systolic areas were significantly increased and right ventricular area SF decreased significantly compared with those values in fetuses without ductal constriction (186 +/- 48 vs. 150 +/- 30 mm2, 112 +/- 34 vs. 81 +/- 19 mm2 and 0.40 +/- 0.05 vs. 0.47 +/- 0.03, respectively, p < 0.01) without any significant changes in left ventricular area SF. Serial studies were available in eight ductal constriction fetuses before and during indomethacin administration, and after withdrawal of the drug for a mean of 24 h. Both systolic and diastolic ductal flow velocities in all fetuses returned to normal range after discontinuation of the drug. During ductal constriction during indomethacin therapy, right ventricular end-diastolic and end-systolic cavity areas were significantly larger and area SF was significantly less than those values before and after the therapy (179 +/- 38 vs. 157 +/- 30 and 154 +/- 27 mm2, 108 +/- 33 vs. 82 +/- 15 and 83 +/- 15 mm2 and 0.40 +/- 0.07 vs. 0.48 +/- 0.03 and 0.46 +/- 0.03, respectively, p < 0.01). This study suggests that ductal constriction influences right ventricular systolic performance.

Development of systemic to pulmonary collateral arteries in premature infants.

Infants with congenital heart disease and chronic lung disease are at risk for development of systemic-to-pulmonary collateral arteries (SPCA). This study characterizes associated clinical findings in 20 premature infants without CHD who were diagnosed as having SPCA with echocardiography. SPCA can occur in premature infants without chronic lung disease and may represent a transient phenomenon.

Transballoon intravascular ultrasound imaging during balloon angioplasty in animal models with coarctation and branch pulmonary stenosis.

BACKGROUND: Intravascular ultrasound (IVUS) studies performed after balloon dilation provide a method for evaluating the adequacy of angioplasty and the nature of associated changes in vessel walls. Previously, IVUS studies required the use of separate scanning catheters inserted independently before and after balloon angioplasty. We tested a 0.035-in, 30-MHz IVUS transducer wire that images from within commercially available 5F balloon dilation catheters. METHODS AND RESULTS: Seven stenoses were created in the left pulmonary artery (n = 3) and in the aortic isthmus (n = 4) in six lambs (weight, 3.4 to 12.5 kg). The balloon catheter selected was advanced across the stenotic area and the IVUS wire advanced in the guide lumen to the center of the balloon. Continuous IVUS images were obtained through balloons before, during, and after dilation. Transballoon imaging confirmed balloon location within the stenotic segment. Luminal diameters of stenotic and adjacent vessel segments before and after angioplasty by IVUS showed good correlation with angiographic measurements (r = .93, P < or = .001). After successful dilation, imaging during deflation allowed the assessment of vascular elastic recoil, mural dissection, and luminal size without requiring changes in balloon position. Repeat dilation could be undertaken and the inflation pressure and technique modified on the basis of the observed results. CONCLUSIONS: This transballoon IVUS system provides important on-line information about lumen diameter and wall structure for evaluation of angioplasty without the need for catheter changes, providing a method to possibly reduce the likelihood of excessive wall damage and to potentially reduce the number of angiograms required to accomplish and confirm results.

Echocardiographic indexes of rejection in pediatric cardiac transplant recipients managed without maintenance steroid immunosuppression.

Several noninvasive echocardiographic indexes were found to correlate with biopsy-confirmed cardiac rejection. Of these, changes in the diastolic flow profile across the mitral valve showed the best correlation.

Doppler echocardiographic evaluation of ventricular diastolic filling in fetuses with ductal constriction.

To assess ventricular diastolic filling in fetuses with constriction of ducts arterious, 43 fetuses of pregnant women receiving indomethacin (100 to 150 mg/day) were examined with Doppler echocardiography. Ductal constriction occurred in 21 fetuses, defined as maximal systolic velocity > 140 cm/s and diastolic flow velocity > 30 cm/s. The variables measured to assess diastolic function were peak velocity during early diastole (peak E wave), peak velocity during atrial contraction (peak A wave), and the velocity ratio (peak E/A ratio); these were compared to maximal ductal flow velocity during systole and diastole. The mitral peak E wave, peak A wave, and peak E/A ratio in fetuses with ductal constriction showed no significant difference from those in fetuses without ductal constriction. In fetuses with ductal constriction, the tricuspid A wave increased significantly without changes in the peak E wave (57 +/- 9 vs 50 +/- 6 cm/s, p < 0.01) and the peak E/A ratio was significantly lower than in fetuses without ductal constriction (0.57 +/- 0.10 vs 0.65 +/- 0.08, p < 0.05). In 9 fetuses with ductal constriction, we compared the Doppler tricuspid E wave, A wave, and E/A ratio during indomethacin administration with those after withdrawal of the drug for a mean of 24 hours. Both systolic and diastolic ductal flow velocities in the fetuses returned to normal range after discontinuation of indomethacin. The tricuspid peak A wave decreased (59 +/- 9 vs 50 +/- 11 cm/s) and the E/ A ratio increased significantly (0.56 +/- 0.07 vs 0.69 +/- 0.07) (both p < 0.01) without any significant change in peak E wave after discontinuation of indomethacin. This study suggests that ductal constriction influences Doppler patterns of right ventricular diastolic filling. These changes could be related to the increased afterload presented to the right ventricle which might affect diastolic function.

Gestational age- and growth-related alterations in fetal right and left ventricular diastolic filling patterns.

To evaluate the effects of gestational age on left and right ventricular diastolic filling in human fetuses, we retrospectively reviewed the diastolic flow velocity patterns through mitral and tricuspid valves in 307 normal fetuses aged 17 to 39 weeks' gestation. The subjects were divided into 3 age groups; 17 to 24 weeks, 25 to 31 weeks, and 32 to 39 weeks. The variables measured were peak flow velocities of early diastole (peak E wave), of atrial contraction (peak A wave), and the velocity ratio (peak E/A ratio). As a whole, the transmitral peak E wave and peak E/A ratio correlated with age using a second-order polynomial curve fit. The strength of the linear correlation between age and transmitral peak E wave and peak E/A ratio and the slope of the relation were greater in the group aged 32 to 39 weeks than in group aged 25 to 31 weeks. Similar temporal change was observed in the relation between age, transtricuspid peak E wave, and peak E/A ratio. The peak A wave for both atrioventricular valves showed little change with gestational age. Contrary to the accepted concept that fetal peak E wave and peak E/A ratio increases linearly with aging, this study shows that early diastolic filling increases mainly after 25 weeks' gestation. We speculate that the maturational changes in ventricular properties in human fetuses accelerate after midgestation.

Right ventricular function in chronically anemic fetal lambs.

OBJECTIVE: Our purpose was to determine whether the increase in extravascular fluid in chronic fetal anemia occurs either because of heart failure or despite successful cardiac adaptation. STUDY DESIGN: Right ventricular function curves were obtained in five ovine fetuses at the start, midpoint, and end of 5 to 8 days of anemia induced by isovolemic daily hemorrhage. Least-squares fit of the ascending and plateau lines of stroke volume versus right atrial pressure were used to establish breakpoints (intersection of the ascending and plateau lines), which were compared by analysis of variance for repeated measures. Myocardial blood flow was measured by microspheres. RESULTS: Carotid arterial oxygen content was reduced from 7.0 +/- 0.3 to 2.1 +/- 0.1 ml/dl and the hematocrit from 29% +/- 1.8% to 13% +/- 0.6%. Breakpoint analysis of function curves showed that although right atrial pressure remained unchanged (3.4 +/- 0.7 and 3.6 +/- 0.6 mm Hg) stroke volume increased from 1.03 +/- 0.14 to 1.62 +/- 0.25 ml/kg. Both right and left ventricular coronary blood flow were increased, 1351 +/- 313 and 1166 +/- 264 ml/min per 100 gm. Excess fluid was present in abdomen and chest of most animals at autopsy. CONCLUSION: Tissue edema during severe anemia occurs despite normal right atrial pressure, increased stroke volume, and markedly increased coronary blood flow, markers of successful cardiac adaptation.

Echocardiographic imaging techniques with subcostal and right parasternal longitudinal views in detecting sinus venosus atrial septal defects.

Sinus venosus atrial septal defects are frequently missed and difficult to visualize with conventional two-dimensional echocardiographic views. Using modified subcostal and right parasternal longitudinal views, nine patients were found to have a sinus venosus atrial septal defect. The modified subcostal view showed a sinus venosus atrial septal defect in all nine patients; three patients had secundum atrial septal defects as well. The right parasternal view detected only six patients with sinus venosus atrial septal defect. Partial anomalous pulmonary venous return was diagnosed in seven patients using these views. The combination of subcostal and right parasternal longitudinal imaging views will improve the detection of sinus venosus atrial septal defects.

Pediatric echocardiography: current role and a review of technical advances.

Advances in echocardiography have enhanced our diagnostic imaging capabilities for congenital heart defects. In addition to improved resolution of two-dimensional images, cardiac hemodynamic assessment is possible with the use of Doppler, color Doppler, and stress echocardiography. Transesophageal echocardiography has allowed intraoperative assessment of cardiac repairs, and fetal echocardiography has allowed development of the field of fetal cardiology. The developing areas of intravascular ultrasonography and three-dimensional echocardiography show promise for the future. Echocardiography continues to revolutionize our ability to diagnose congenital heart defects accurately.

Nitric oxide is an important determinant of coronary flow at rest and during hypoxemic stress in fetal lambs.

Fourteen fetal lambs were instrumented with atrial, coronary sinus, and arterial catheters and a proximal left circumflex coronary artery Doppler probe and were studied at a mean gestational age of 130 +/- 3 (SD) days, 7 +/- 2 days after surgery. Myocardial blood flow was assessed using 15-microns microspheres and Doppler flow velocities. In 11 fetuses, the maximal myocardial flow response to left atrial adenosine infusion was 802 +/- 215 ml.min-1 x 100 g-1, 3.5-fold greater than baseline flow. Acute fetal hypoxemia in six fetuses to an arterial PO2 of 8.8 +/- 0.8 mmHg and an arterial O2 content (CaO2) of 1.7 +/- 0.2 ml/dl was not associated with significant change in coronary perfusion pressure; yet left ventricular myocardial flow increased to 1,020 +/- 198 ml.min-1 x 100 g-1, a value significantly greater than that seen with adenosine (P < 0.05). Left atrial N omega-nitro-L-arginine (L-NNA), a competitive inhibitor of nitric oxide synthase (NOS), was infused at a dosage of approximately 1 mg.kg-1.min-1 for 60 min in 10 fetuses. Although L-NNA was associated with a significant increase in arterial pressure, left ventricular myocardial flow decreased (162 +/- 79 ml.min-1 x 100 g-1) as did myocardial O2 consumption (P < 0.05). Acute hypoxemia in five fetuses that received L-NNA was associated with significant further increases in systemic arterial pressure; however, left ventricular myocardial flow was only 771 +/- 237 ml.min-1 x 100 g-1, a value similar to that seen with adenosine and approximately 75% of that seen with acute hypoxemia alone. We conclude that nitric oxide plays an important role in the regulation of fetal myocardial flow during basal conditions as well as in the exuberant vasodilatory response associated with acute hypoxemic stress.

Balloon aortic valvuloplasty for aortic stenosis in neonates, children, and young adults.

Balloon aortic valvuloplasty is a safe and effective treatment for aortic stenosis in neonates, children, and young adults. The indication for balloon valvuloplasty in children is a peak systolic gradient > 70 mmHg or > 50 mmHg in any patient with symptoms. Published results indicate that the procedure results in an acute reduction in gradient ranging from 49%-70%, and this reduction appears to persist through at least an intermediate follow-up. The percentage reduction in gradient is similar for neonates as well as older children. In neonates, it is imperative to evaluate the size of the left ventricle prior to balloon valvuloplasty since mortality is highest in those with variants of hypoplastic left heart syndrome. Though morbidity and mortality is higher in the neonatal age group, the results are similar to those following surgical intervention. In children older than 1 month of age, the major complication is the development of aortic regurgitation, although it usually appears to be well-tolerated. Previous surgical valvotomy is not a contraindication to balloon aortic valvuloplasty. In the current era, we believe that balloon aortic valvuloplasty should be considered as the first option in neonates, children and young adults with significant aortic valve obstruction.

Comparison of four Doppler echocardiographic methods for calculating pulmonary-to-systemic shunt flow ratios in patients with ventricular septal defect.

Several methods currently exist for quantifying pulmonary (Qp) and systemic (Qs) shunt flow using Doppler echocardiography, although none is widely utilized. In this study, 39 patients (age 2 months to 12 years, mean 2.1 years) underwent an echocardiographic examination within 1 month of Qp:Qs shunt flow determination by oximetry at catheterization. Qp:Qs was determined by 4 methods that utilized: (1) velocity time integrals and luminal areas to estimate volume flow of the pulmonary artery and aorta; (2) the square of the ratios of pulmonary artery to aorta, multiplied by the ratio of pulmonary to aortic peak flow velocities; (3) inclusion of mitral and tricuspid valve volume flow to pulmonary and aortic volume flow; and (4) ventricular septal defect (VSD) diameter and velocity time integral to calculate left-to-right shunt, which, when added to aortic volume flow (Qs), can be used to estimate Qp. Each of the first 3 methods was statistically correlated to the oximetry Qp:Qs, with r values ranging from 0.54 to 0.66 (p < 0.001). However, the fourth method, based on direct computation of flow across the VSD, had the best correlation to catheterization data (r = 0.82), and further improved when 7 patients with a large VSD (> 9 mm/m2), all of whom had bidirectional shunting, were removed (r = 0.90). Thus, we concluded that this latter method demonstrated the best correlation to catheterization-derived shunt flow data, and because this method is somewhat less labor-intensive than the others, should provide clinically useful data well suited for serial evaluation in infants and children with VSD.

Effects of ductus arteriosus occlusion on pulmonary artery pressure during in utero ventilation in fetal sheep.

Seven fetal sheep were prepared to study the short-term effects of in utero ventilation and ductus arteriosus occlusion on pulmonary artery pressure and on fetal right ventricular function assessed using the right atrial pressure-right ventricular stroke volume relationship. Nine days post-surgery (140 days gestation), blood gas and haemodynamic values were obtained before and during in utero ventilation with 100% O2, and during ventilation with the ductus arteriosus occluded. Oxygen content increased significantly from 7.2 to 14.5 ml dl-1 with ventilation and remained elevated at 14.4 ml dl-1 with ventilation with the ductus arteriosus occluded. In utero ventilation produced a left to right atrial pressure gradient and depression of the right atrial pressure-right ventricular stroke volume relationship. Ductus arteriosus occlusion during in utero ventilation reduced the left to right atrial pressure gradient, and along with a decrease in pulmonary artery pressure, resulted in an upward shift of the right atrial pressure-right ventricular stroke volume relationship, but only to the preventilation level. This study indicates that the fetal right atrial pressure-right ventricular stroke volume relationship is significantly altered, both by changes in the left to right atrial pressure gradient and by changes in pulmonary artery pressure seen with in utero ventilation and subsequent ductus arteriosus occlusion.