Population-based review of tetralogy of Fallot with absent pulmonary valve: is prenatal diagnosis really associated with a poor prognosis?

OBJECTIVES: Tetralogy of Fallot with absent pulmonary valve syndrome (TETAPV) is reported in obstetric literature to have an extremely poor prognosis. We sought to determine the clinical outcome associated with TETAPV and whether prenatal diagnosis confers a poor prognosis. METHODS: All cases of TETAPV diagnosed in British Columbia between 1980 and 2009 were reviewed and grouped according to time of diagnosis, either prenatal or postnatal. The groups were compared with respect to mortality, respiratory problems, number of interventions and functional capacity at last follow-up. RESULTS: Eight and 11 patients were included in the prenatally and postnatally diagnosed groups, with overall long-term survival of 71% and 82%, respectively. There was no significant difference in mortality, frequency of preoperative intubation, number of interventions or functional capacity between groups. CONCLUSION: From a population-based retrospective analysis of TETAPV cases identified over three decades it is concluded that the prognosis for TETAPV is better than that previously reported in the obstetric literature. This information should be used to guide prenatal counseling.

Endothelial dysfunction and compromised eNOS/Akt signaling in the thoracic aorta during the progression of Marfan syndrome.

BACKGROUND AND PURPOSE: Aortic complications account for the major mortality in Marfan syndrome (MFS), a connective tissue disorder caused by mutations in FBN1 encoding fibrillin-1. We hypothesized that MFS impaired endothelial function and nitric oxide (NO) production in the aorta. EXPERIMENTAL APPROACH: Mice (at 3, 6, 9 and 12 months of age) heterozygous for the Fbn1 allele encoding a cysteine substitution (Fbn1 (C1039G/+), Marfan mice, n=75), the most common class of mutation in MFS, were compared with age-matched control littermates (n=75). Thoracic and abdominal aortas from the two groups were studied. KEY RESULTS: Isometric force measurements revealed that relaxation to ACh (but not to sodium nitroprusside) was diminished in the phenylephrine-precontracted Marfan thoracic aorta at 6 months of age (pEC(50)=6.12+/-0.22; maximal response, E(max)=52.7+/-6.8%; control: pEC(50)=7.34+/-0.19; E(max)=84.8+/-2.2%). At one year, both inhibition of NO production with N(omega)-nitro-L-arginine methyl ester, or denudation of endothelium increased the phenylephrine-stimulated contraction in the control thoracic aorta by 35%, but had no effect in the Marfan aorta, indicating a loss of basal NO production in the Marfan vessel. From 6 months, a reduced phosphorylation of endothelial NOS (eNOS)(Ser1177) and Akt(Thr308) detected by Western blotting was observed in the Marfan thoracic aorta, which was accompanied by decreased levels of cGMP. Expressions of Akt and eNOS in the abdominal aorta were not different between the two groups. CONCLUSIONS AND IMPLICATIONS: MFS impairs endothelial function and signaling of NO production in the thoracic aorta, suggesting the importance of NO in the age-related progression of thoracic aortic manifestations.

Effect of pressure loading, volume loading and surgery on left ventricular chamber and myocardial stiffness in congenital heart disease, with a reevaluation of normal pediatric values.

This study assessed the effect of pressure load, volume load and surgery on left ventricular chamber stiffness (b) and myocardial stiffness (k). A normal range for chamber stiffness and myocardial stiffness was also established. A total of 44 patients were studied: 8 were control subjects, 12 had volume load and 24 had pressure load. At cardiac catheterization simultaneous high fidelity pressures (P) and left ventricular volumes (V) were obtained in one diastolic cycle. From the relation P = aVb, operant chamber stiffness (b) was estimated for each patient. Similarly, the relation between stress (sigma) and radius (B) was approximated by sigma = cBf and the myocardial stiffness (k) derived for each patient. Mean values for chamber or myocardial stiffness for the diagnostic groups were not significantly different but differed within the operative groups. Mean values for b and k were greater in the post-open heart surgery group than in the post-closed heart surgery or nonsurgical group. Although the mean values for chamber stiffness and myocardial stiffness for the diagnostic groups were not different, there were more abnormal patients in the pressure load group (9 of 24) than in the volume load group (2 of 8) when the normal range was obtained from the control group. Thus, left ventricular operant chamber and myocardial stiffness are often preserved with volume loading, less frequently with pressure loading and rarely after open heart surgery.

Noninvasive assessment of left ventricular function related to serum digoxin levels in neonates.

Eighteen neonates in heart failure were investigated to assess whether high or low serum digoxin levels had differing effects on left ventricular function as determined by systolic time intervals obtained by echocardiography. Nine patients had digoxin levels of 1.99 +/- 0.35 ng/ml (group 1). Nine others had levels of 3.62 +/- 0.95 ng/ml (group 2). Systolic time intervals were obtained by echocardiography before and at 5 days after digoxin and correlated with serum levels. The heart rate, preejection period (PEP), left ventricular ejection time (LVET), electromechanical systole (QS2) and the PEP/LVET ratio were measured. LVET and electromechanical systole were indexed. These measurements were analyzed and the two groups were compared using Student's t test. The clinical improvement in both groups was similar and no difference in ECG changes were noted. Therapy with digoxin produced changes in heart rate and systolic time intervals in both groups. Both showed significant shortening of electromechanical systole index; group 1 significantly shortened the LVET index and PEP/LVET ratio, whereas group 2 significantly shortened the PEP. Statistical analysis comparing the two groups showed no difference between them. Digoxin produces measurable changes in the indices of left ventricular function. The magnitude of these changes suggests no therapeutic advantage to the higher levels.

Determination of left ventricular diastolic chamber stiffness and myocardial stiffness in patients with congenital heart disease.

Left ventricular diastolic indexes were derived in 13 patients aged 5 to 21 years. Three had a normal heart, three had lesions causing volume overload and seven had coarctation of the aorta, including one whose main lesion was severe endocardial fibroelastosis. At cardiac catheterization simultaneous high fidelity pressure (P) and left ventricular volume (V) measurements were obtained and several points in one diastolic cycle taken. With use of a monoexponential formula (P = aebv) for P versus V, dP/dv and the operant chamber stiffness b were obtained. Similarly, with use of sigma = alpha e beta epsilon, d sigma/d epsilon, elastic stiffness (E) and the muscle stiffness constant KE were obtained. Values for b were 0.0273 +/- 0.0065 in normal subjects, 0.017 +/- 0.0043 in those with volume overload, 0.0369 +/- 0.0173 in those with coarctation (without endocardial fibroelastosis) and 0.0192 in the child with endocardial fibroelastosis. The plot of P versus V for coarctation was to the left and steeper than normal and the patients with volume overload had a flattened rightward curve, whereas the curve for those with endocardial fibroelastosis was extremely rightward. The stress-radii curves of the normal subjects and those with coarctation were similar whereas the curves for patients with volume overload and endocardial fibroelastosis were rightward of normal. The value for KE was 8.92 +/- 0.87 for the normal subjects, 8.26 +/- 0.75 for those with volume overload, 9.2 +/- 2.5 for those with coarctation and 22.75 for those with endocardial fibroelastosis. Thus, the pressure-loaded ventricle is stiffer than the normal, which in turn, is stiffer than the volume-loaded ventricle. This response, due to hypertrophy, appears to be appropriate in that diastolic stress was normalized and muscle stiffness was not increased except in the patient with endocardial fibroelastosis.

Systolic and diastolic function in tricuspid valve atresia before the Fontan operation.

Systolic and diastolic function were assessed at preoperative cardiac catheterization in 6 patients with classic tricuspid atresia and were compared with those in control subjects. All patients had systemic-to-pulmonary shunts. Left ventricular end-systolic and end-diastolic volumes and masses were significantly larger in the patient group; stroke volume and the ratio of volume to mass were also higher, but not significantly. Mean end-diastolic, peak systolic and end-systolic pressures were similar. Mean stress at end-systole and peak systole were significantly higher in the patient group. Operant chamber stiffness tended to be lower than normal, but was not statistically significant, and myocardial stiffness was normal for the patient group also. Indexes of systolic function were compared. The rate-corrected mean velocity of fiber shortening in the patient group was lower and its relation with stress at end-systole was variable with 4 abnormal patients. The ratio of stress at end-systole/end-systolic volume was significantly lower in patients. The duration of hospital stay did not correlate with end-diastolic volume or any parameter. Thus, this study found abnormalities of load-dependent and independent indexes of systolic function with normal diastolic function in young preoperative patients with tricuspid atresia.

Left ventricular systolic and diastolic function after total correction of tetralogy of Fallot.

Left ventricular (LV) systolic and diastolic function was assessed in 12 patients after total correction of tetralogy of Fallot (age range 5 to 18 years, mean 10) and compared with 10 control patients. Only 1 patient had a shunt before total correction that was performed at a mean age of 3.5 years, (range 0.3 to 8). At cardiac catheterization the following indexed LV parameters were measured: end-diastolic and end-systolic volumes, wall mass, ejection fraction, stroke volume and end-diastolic and end-systolic pressures and stresses. The rate-corrected mean velocity of fiber shortening was calculated. LV diastolic operant chamber stiffness and myocardial stiffness were calculated from simultaneous diastolic pressures and volumes in mid- and late diastole using monoexponential formulas. The 2 groups were compared by unpaired t tests. The tetralogy group had higher mean end-diastolic (93 vs 74 ml/m2), end-systolic (29 vs 19 ml/m2) and stroke (64 vs 55 ml/m2) volumes than controls. Rate-corrected mean velocity of fiber shortening was lower in the tetralogy group (1.07 vs 1.24). Myocardial stiffness was higher in the tetralogy group (16 vs 11). Other indexes were not significantly different. Thus, LV function after total correction of tetralogy of Fallot may be abnormal with larger than normal LV size, decreased contractile function and increased myocardial stiffness.

Rate-corrected mean velocity of fiber shortening-stress at peak systole as a load-independent measure of contractility.

The relation of mean velocity of fiber shortening-stress at end-systole is a good load-independent index of left ventricular contractility, but involves simultaneous M-mode echocardiography, carotid tracing and blood pressure determination, which may be impractical in children. As stress at peak systole and end-systole are closely related, this study examined whether the relation of mean velocity of fiber shortening-stress at peak systole could be used as a simpler method of assessing left ventricular contractility in a normal population of children. In addition, the cross-sectional normal range for a pediatric population was obtained. In 25 normal children aged 4 to 17 years (mean age 11), rate-corrected mean velocity of fiber shortening (MVCFc), stress at peak systole (sigma PS), and end-systolic stress (sigma ES) were determined using echocardiography, carotid pulse tracing and blood pressure measurement. Six patients with cardiomyopathy (mean age 8 years) were also studied. The relation of stress at peak systole and end-systolic stress was sigma PS = 1.004 sigma ES + 12.0 (r = 0.91, SEE = 4.98; p less than 0.001) for the normal group, and sigma PS = 1.083 sigma ES + 7.7 (r = 0.99, SEE = 4.07; p less than .001) for the cardiomyopathic group. This slope of the regression line was slightly higher and the difference was statistically significant. The slope of MVCFc = 0.0066 sigma PS + 1.55 (SEE = 0.131, r = -0.52) was nearly identical to that of MVCFc = 0.0065 sigma ES + 1.46, (SEE = 0.135, r = -0.46), with no difference in the regression coefficients.(ABSTRACT TRUNCATED AT 250 WORDS)

Congenital heart disease and Robinow syndrome: coincidence or an additional component of the syndrome?

We report on a girl with Robinow syndrome and pulmonary atresia with ventricular septal defect (VSD). Seven cases of Robinow syndrome with congenital heart defect (CHD) have now been described, 5 of whom had stenosis or atresia of the pulmonic valve. This suggests that CHD, especially right ventricular outlow obstruction, may be a component manifestation of this syndrome in some cases. Since early recognition of this type of heart lesion can minimize morbidity by facilitating optimal surgical therapy, thorough cardiac evaluation of all patients with Robinow syndrome seems warranted.

Vascular abnormalities in Adams-Oliver syndrome: cause or effect?

We describe a young girl diagnosed with the Adams-Oliver syndrome (AOS) associated with double outlet right ventricle, portal hypertension, and pulmonary hypertension. We hypothesize that a congenital vascular abnormality is the underlying pathogenesis and that the cutaneous defects characteristically seen in AOS represent the most common manifestation of this. We suggest that AOS should not merely be considered a syndrome consisting of aplasia cutis congenita and terminal transverse limb defects but rather a constellation of clinical findings resulting from an early embryonic vascular abnormality.

The clinical value and risks of lung biopsy in children with congenital heart disease.

A retrospective review was made of 59 open lung biopsy specimens taken between 1984 and 1988 from children with congenital heart disease who were at risk for pulmonary vascular disease. Thirty-seven patients (ranging in age from 3.5 months to 23 years; median age, 14 months) had a primary left-to-right shunt (group A) and 22 patients (ages 1 to 15 years) had palliated cyanotic heart disease (group B). Forty-five of the lung biopsy specimens were requested as frozen sections. In both groups lung biopsy specimens were graded by the Heath-Edwards classification and correlated against preoperative hemodynamic data and outcome. In group A patients, carefully measured pulmonary vascular resistance and pulmonary/systemic vascular resistance ratio were reliable indicators of the structural state of the pulmonary vascular bed, obviating the need for routine lung biopsy. Pulmonary/systemic vascular resistance ratios greater than 0.45 accurately predicted all patients with irreversible pulmonary vascular disease, and pulmonary vascular resistance greater than 7 units.m2 accurately predicted all but one case of disease. Reversibility of pulmonary vascular changes is not synonymous with immediate postoperative survival: Fatal postoperative pulmonary hypertensive crises occurred in the presence of reversible pulmonary disease. Of those considered for the Fontan procedure, a mean pulmonary artery pressure less than 30 mm Hg and pulmonary vascular resistance less than 3 units.m2 correlated with Heath-Edwards grade I or normal lung biopsy results. In 36% of group B patients, reliable assessment of pulmonary vascular resistance could not be made, indicating a possible need for open lung biopsy procedures. When lung biopsy procedures were used as an isolated procedure, they were more dangerous (20% mortality, 13% morbidity) than previously reported. Intraoperative frozen sections are not adequate to accurately assess pulmonary vascular changes (9% error); serial paraffin sections are required.

Successful palliation by pulmonary artery banding in absent pulmonary valve syndrome with aneurysmal pulmonary arteries.

Three infants with absent pulmonary valve syndrome were treated between 1977 and 1980. All infants were in critical cardiorespiratory failure refractory to medical therapy. Pulmonary artery banding was performed to reduce the volume occupied by the large pulsating pulmonary artery in a limited mediastinal space. The band reduced tracheobronchial compression and increased effective cardiac output. All three infants survived the procedure and, at follow-up, significant improvement in cardiorespiratory function has been noted, with satisfactory growth. This experience suggests that pulmonary artery banding has a place in the initial management of absent pulmonary valve syndrome, allowing survival so that total correction can be undertaken more safely at a later stage.

Outcome of fetuses diagnosed with atrioventricular septal defect.

OBJECTIVE: To quantify the association of prenatally diagnosed atrioventricular septal defect with Down syndrome and to evaluate its impact on obstetric and neonatal outcomes. METHODS: Charts of 42 cases of atrioventricular septal defect diagnosed by fetal echocardiography from July 1985 to July 1997 were reviewed for prenatal history and outcome data (pregnancy outcome, pathologic confirmation, postnatal echocardiographic findings, and neonatal outcome). Statistical analysis was done using Fisher exact test and odds ratios. RESULTS: The mean gestational age at diagnosis was 26 weeks. Four cases could not be confirmed antenatally on repeat echocardiograms and were excluded. Reasons for referral of the remaining 38 fetuses included an abnormal four-chamber view in 76%. Twenty-two fetuses (58%) had abnormal karyotypes: 19 trisomy 21, one trisomy 18, one trisomy 13, and one mosaicism. The cardiac lesions were isolated in 20 fetuses (53%). After excluding cases of termination, ten of 12 fetuses (83%) with Down syndrome survived, compared with seven of 13 (54%) with normal karyotypes (P = .125). The odds of trisomy 21 were 16 times higher (95% confidence interval 3.0, 85.3) in fetuses with isolated cardiac lesions compared with those with associated cardiac anomalies. CONCLUSION: Prenatal diagnosis of atrioventricular septal defect was associated with a 58% risk of aneuploidy (mainly trisomy 21). Down syndrome fetuses with this cardiac anomaly appeared to have a better survival rate than fetuses with normal karyotypes. Our sample did not have enough power to show a statistically significant difference. When an isolated atrioventricular septal defect was diagnosed prenatally, the odds of trisomy 21 were significantly higher than when other associated cardiac lesions were diagnosed. This information should be considered in prenatal counseling for atrioventricular septal defect.

Fetal echocardiography: results in high-risk patients.

The results of 140 fetal cardiac scans in 124 high-risk obstetric patients (16 to 40 weeks' gestation) are presented. Sixty patients were scanned for high genetic or environmental risk (group 1); 31 because of fetal abnormality detected on routine ultrasound scanning (group 2) and 37 because of arrhythmias (group 3). Three patients were in two groups. The standard echocardiography views, ie, long-axis, great vessel short axis, four chamber, and aortic arch were obtained in 72, 95, 96, and 55%, respectively. All scans in group 1 were diagnosed as normal. In group 2, complex cardiac abnormalities were detected, the presence of fetal cardiac failure and its cause were clarified, and serious cardiac malformations were excluded. Arrhythmias in group 3 were diagnosed correctly and fetal hemodynamics assessed. A small number of lesions were not detected or diagnosed. The factors interfering with detection of lesions were abnormalities of the intrathoracic or abdominal cavity, inadequate amniotic fluid, and size of lesions. Major cardiac structures or abnormalities could be identified, and abnormal hemodynamics caused by arrhythmias and structural lesions assessed. Unnecessary intervention was prevented in five cases and conversely the need for acute intervention was indicated in seven cases. Fetal echocardiography remains a specialized investigation that has an important role in the management of some high-risk pregnancies.

Pulmonary artery banding: results and current indications in pediatric cardiac surgery.

The results of pulmonary artery banding in 144 patients seen from 1971 to 1984 were reviewed. Age ranged from 1 week to 4 years (median, 8 weeks) and weight, from 1.1 to 16 kg (median, 4 kg). The patients were divided into three major groups: Group 1, defects without mixing disorders (ventricular septal defect, double-outlet right ventricle [DORV], atrioventricular septal defect); Group 2, defects with mixing disorders (transposition of the great arteries, DORV, single ventricle, tricuspid atresia); and Group 3, miscellaneous (mitral atresia, left ventricular hypoplasia, truncus complex). The diagnostic group influenced survival (p = 0.0035). In Group 1, 88.8% survived, but only 64.9% survived in Groups 2 and 3 combined. The presence of patent ductus arteriosus or coarctation of the aorta had no effect on survival (p = 0.61 and p = 0.7, respectively). The clinical condition at thirty days after pulmonary artery banding was good in 35.1% and fair in 46.9% of the patients. When the data were divided into the three periods 1971 through 1974, 1975 through 1979, and 1980 through 1984, which included 28, 49, and 67 patients, respectively, a significant improvement in survival was observed from the early (64.3%) to the late period (92.5%) (p = 0.0009). Patients weighing less than 4 kg had a significantly lower survival in the period 1971 through 1974 (37.5% versus 91.67%). No significant difference in survival was detected in the late period, 1980 to 1984 (90% versus 94.6%), between patients weighing less than and those weighing more than 4 kg. Pulmonary artery banding is clinically satisfactory in small infants and children with complex anomalies.

Treatment of grafts and major vessel thrombosis with low-dose streptokinase in children.

Low-dose streptokinase infusions have been used in 8 of our patients. Five of these were newborns who had major vessel occlusion. Four babies had extensive aortic thrombosis and hypertension producing congestive aortic thrombosis and hypertension producing congestive heart failure. One baby had caval and renal vein thrombosis and was in renal failure. Two infants with cyanotic heart disease and 1 with arteritis had occluded prosthetic grafts, which were reopened completely. Two grafts were between the subclavian and pulmonary arteries (Blalock-Taussig shunt), and one was between the abdominal aorta and right renal artery. In each patient, the thrombolytic agent was delivered directly to the area of thrombosis by three or four percutaneously inserted French catheters. The dose of streptokinase used was between 50 and 100 U/kg/hr. Therapy lasted for 2 to 11 days. Major bleeding was anticipated, and it occurred in 1 patient. Low-dose streptokinase infusion is a safe and effective treatment for a variety of thrombotic problems in infants and children.

Short- and long-term variability of echocardiographic stress-velocity indexes of cardiac function in a pediatric population.

This study determined the short- and long-term variability of stress-velocity relationships at end systole and peak systole. A prospective study during the short term (0 to 15 and 0 to 30 minutes) and long term (0 to 1 and 0 to 12 months) was performed calculating variability by the limits of agreement method. The study was performed in a tertiary-care pediatric echocardiographic laboratory. Twenty-five normal children underwent repeat testing as described. Standard blood pressure, carotid pulse tracing, and M-echocardiography of the left ventricle was performed at the intervals described. The rate-corrected mean velocity of fiber shortening (MVCFC), echocardiographic stress at end systole (SES), and echocardiographic stress at peak systole (SPS) were calculated for all recordings. The slopes of MVCFC-SES and MVCFC-SPS were determined by regression and plotted. With these slopes, the second and third stress values were normalized to the first stress value for the short and long term. The differences in normalized MVCFC and MVCFC (delta MVCFC) for 15 to 0 minutes, 30 to 0 months, 1 to 0 month, and 12 to 1 month were obtained for both SES and SPS, and 95% limits of agreement were estimated. The mean delta MVCFC for SES and SPS for the short and long term were not different from 0 or each other, indicating no bias. The 95% limits of agreement of delta MVCFCs (i.e., variability for SES at 15 to 0 minutes, 30 to 0 minutes, 1 to 0 month, and 12 to 0 month) were +/- 0.18, +/- 0.24, +/- 0.34, and +/- 0.27, respectively, and for SPS +/- 0.18, +/- 0.24, +/- 0.33, and +/- 0.28. Variability showed an increasing trend with time but was significant only from 15 to 0 minutes and 1 to 0 month (p = 0.006). This study has established short- and long-term variability in the stress-velocity relationship that is essential for monitoring acute and chronic changes in ventricular contractility in an individual patient.

Assessment of bedside umbilical vein balloon septostomy using two-dimensional echocardiographic guidance in transposition of great arteries.

The effectiveness of "bedside" balloon atrial septostomy via the umbilical vein using 2-dimensional echocardiography was compared to the traditional femoral vein approach using fluoroscopy in a series of neonates with transposition of great arteries from March, 1984 to April, 1987. There were 7 neonates who had balloon septostomy performed at the "bedside" (Group I) compared to 13 who had the procedure performed in the catheterization laboratory (Group II). Group II consisted of 7 newborns who had elective femoral vein catheterization under fluoroscopy (Group IIA) and 6 who failed "bedside" umbilical vein balloon septostomy and subsequently had the femoral vein approach under fluoroscopy (Group IIB). Results showed that adequacy of balloon septostomy was not related to the approach used, with 4 of 7 in Group I and 9 of 13 in Group II with an adequate atrial tear and clinical response. The Delay time to septostomy (i.e. time elapsed from initial assessment to commencement of balloon septostomy) and Procedure time (i.e. time taken to complete the balloon septostomy) was significantly shorter for Group I (mean time = 0.7 hours and 0.26 hours respectively) compared with Group IIA (mean time = 2.6 hours and 1.8 hours) and Group IIB (mean time = 2.4 hours and 1.4 hours). Of note, there was no significant increase in Delay time between Group IIA and IIB.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of echocardiography in pre-operative cardiac catheterization in congenital heart disease.

The influence of echocardiography on pre-operative cardiac catheterization was assessed in a retrospective analysis comparing two 12-month periods. Of 245 operations in 1983, 200 (82%) had pre-operative cardiac catheterization when two-dimensional echocardiography only was used in the pre-operative assessment compared to 162 of 238 (68%) operations in July 1985-June 1986 when pulsed Doppler echocardiography also was used (P less than 0.001). Significant reductions in pre-operative cardiac catheterization were present in both open (87/87 vs 89/102, P less than 0.001) and closed (113/158 vs 73/136, P less than 0.005) heart procedures. The group with the most significant reduction in pre-operative cardiac catheterization before open heart surgery were children with atrial septal defects; of the closed heart surgical groups, the greatest reductions were in patent ductus arteriosus, coarctation of the aorta and tetralogy of Fallot. Echocardiogram diagnostic errors occurred in 22/245 (9%) in 1983 compared to 9/238 (4%) in 1985/86 (P less than 0.05). Echocardiography has resulted in a significant reduction in pre-operative cardiac catheterization and has become more accurate in diagnosis.