Cardiovascular symptoms and signs in evaluating cardiac murmurs in children.

BACKGROUND: The aim of the present study was to determine the usefulness of cardiovascular symptoms and signs in the recognition of significant congenital heart lesions that required surgical or catheter interventions in different pediatric age groups. METHODS: A retrospective chart review was carried out of 110 patients with significant heart anomalies that required surgical or catheter interventions (group I) and 113 children, presenting with cardiac murmurs, with congenital heart conditions not requiring any interventions. (group II). RESULTS: Clinical symptoms or signs were significantly more common in group I than in group II subjects (85% vs 32%, P < 0.0001). The odds of having significant lesions requiring interventions in the presence of either cardiovascular symptoms or signs were 37.5 (95% confidence interval [CI]: 6.5-218.1) for neonates, 14.5 (95%CI: 4.7-51.7) for infants, and 8.0 (95%CI: 3.3-19.2) for children and adolescents. In neonates, the negative predictive values of the absence of symptoms or signs in isolation were relatively low at 64% and 65%, respectively. In children beyond infancy, the positive predictive values of the presence of symptoms or signs in isolation were also low at 62% and 68%, respectively. CONCLUSIONS: Clinical assessment of cardiovascular symptoms and signs remains useful in the evaluation of the significance of pathological cardiac murmurs in children in the present era of technology. Nonetheless, the predictive values vary with different pediatric age groups.

De novo large rare copy-number variations contribute to conotruncal heart disease in Chinese patients.

Conotruncal heart anomalies (CTDs) are particularly prevalent congenital heart diseases (CHD) in Hong Kong. We surveyed large (>500 kb), rare (<1% frequency in controls) copy-number variations (CNVs) in Chinese patients with CTDs to identify potentially disease-causing variations. Adults who tested negative for 22q11.2 deletions were recruited from the adult CHD clinic in Hong Kong. Using a stringent calling criteria, high-confidence CNV calls were obtained, and a large control set comprising 3,987 Caucasian and 1,945 Singapore Chinese subjects was used to identify rare CNVs. Ten large rare CNVs were identified, and 3 in 108 individuals were confirmed to harbour de novo CNVs. All three patients were syndromic with a more complex phenotype, and each of these CNVs overlapped regions likely to be important in CHD. One was a 611 kb deletion at 17p13.3, telomeric to the Miller-Dieker syndrome (MDS) critical region, overlapping the NXN gene. Another was a 5 Mb deletion at 13q33.3, within a previously described critical region for CHD. A third CNV, previously unreported, was a large duplication at 2q22.3 overlapping the ZEB2 gene. The commonly reported 1q21.1 recurrent duplication was not observed in this Chinese cohort. We provide detailed phenotypic and genotypic descriptions of large rare genic CNVs that may represent CHD loci in the East Asian population. Larger samples of Chinese origin will be required to determine whether the genome-wide distribution differs from that found in predominantly European CHD cohorts.

Novel and traditional cardiovascular risk factors in children after Kawasaki disease: implications for premature atherosclerosis.

OBJECTIVES: We determined the profile of cardiovascular risk factors in children late after Kawasaki disease (KD) and compared it with that of age-matched healthy children. BACKGROUND: Concerns have been raised regarding the possibility of a predisposition of KD to premature atherosclerosis later in life. METHODS: A cohort of 102 subjects were studied: 37 KD patients with coronary aneurysms (group I), 29 KD patients with normal coronary arteries (group II), and 36 healthy age-matched children (group III). The fasting total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein (apo) A-I, apoB, and homocysteine levels were compared among the three groups. In addition, blood pressure and brachioradial arterial stiffness, as determined by pulse wave velocity (PWV), were measured and compared. RESULTS: Group I subjects had lower HDL cholesterol (p = 0.016) and apoA-I levels (p = 0.044) and higher apoB levels (p = 0.029) and PWV (p = 0.001) than group III control subjects. Likewise, the apoB levels (p = 0.007) and PWV (p = 0.042) were higher in group II than in III subjects, although their HDL cholesterol (p = 0.54) and apoA-I (p = 0.52) levels were similar. The LDL cholesterol levels were higher in group I and II patients than in controls, although not statistically significant (p = 0.17). Blood pressure and homocysteine levels did not differ among the groups. CONCLUSIONS: An adverse cardiovascular risk profile, as characterized by a proatherogenic alteration of the lipid profile and increased arterial stiffness, occurs in children after KD. The profile is worse in those with than in those without coronary aneurysms.

Doppler tissue imaging analysis of ventricular function after surgical and transcatheter closure of atrial septal defect.

The long-term ventricular function of children after surgical and transcatheter closure of secundum atrial septal defects was assessed by Doppler tissue imaging and compared with that of age-matched controls. Long-term right ventricular function was impaired in patients after surgical repair, as reflected by decreased systolic and diastolic tricuspid annular velocities and an increased Tei index. In contrast, right ventricular function was preserved after transcatheter device closure.

Impact of preoperative aortic cusp prolapse on long-term outcome after surgical closure of subarterial ventricular septal defect.

BACKGROUND: Previous reports on the long-term outcome of surgical closure of subarterial ventricular septal defect were based on a relatively small number of patients. METHODS: We reviewed the long-term outcome of 135 patients who underwent closure of their defect and, in light of the findings, assessed the impact of preoperative aortic cusp prolapse and surgical interventions on occurrence of aortic regurgitation (AR) in the long-term. The patients were categorized into three groups for comparison: group I consisted of 79 patients with no aortic cusp prolapse and underwent simple closure of ventricular septal defect, group II comprised 39 patients with mild to moderate cusp prolapse who similarly had only closure of the defect performed, whereas group III comprised 17 patients who had additional aortic valvoplasty for greater than moderate to severe cusp prolapse. RESULTS: Group I patients had significantly higher pulmonary arterial pressure (p < 0.001) and ratio of pulmonary blood flow to systemic blood flow (p < 0.001). None of these patients had AR before their operation, and none experienced AR afterward at a median follow-up of 6.1 years. Of the 39 group II patients, 30 (77%) had trivial or mild AR preoperatively. The AR improved in 15 patients, remained trivial or mild in 14 and absent in 7, but progressed to trivial or mild in 3 at a median follow-up of 3.1 years. None required further interventions. In contrast, 14 (82%) of the 17 group III patients had moderate to severe AR before operation. The regurgitation improved in 10, but remained moderate or severe in 4 and worsened further in 3 at a median follow-up of 4.6 years. The freedom from failure of aortic valvoplasty was (mean +/- standard error of the mean) 71%+/-11%, 64%+/-12%, and 43%+/-19% at 1, 5, and 10 years, respectively. An older age at latest follow-up was the only identifiable significant risk factor (p = 0.03). CONCLUSIONS: Our data do not support the need of aortic valvoplasty for mild to moderate aortic cusp prolapse. Close follow-up is warranted in those with greater than moderate to severe cusp prolapse despite valvoplasty as there is continued failure on follow-up. Nothing, however, is better than early closure of defects before development of aortic valve complications.

Under-recognition of 22q11.2 deletion in adult Chinese patients with conotruncal anomalies: implications in transitional care.

22q11.2 deletion syndrome (22q11.2DS) is a multi-systemic disorder with high phenotypic variability. Under-diagnosis in adults is common and recognition of facial dysmorphic features can be affected by age and ethnicity. This study aims to determine the prevalence of undiagnosed 22q11.2DS in adult Chinese patients with conotruncal anomalies and to delineate their facial dysmorphisms and extra-cardiac manifestations. We recruited consecutively 156 patients with conotruncal anomalies in an adult congenital heart disease (CHD) clinic in Hong Kong and screened for 22q11.2DS using fluorescence-PCR and fluorescence in-situ hybridization. Assessment for dysmorphic features was performed by a cardiologist at initial screening and then by a clinical geneticist upon result disclosure. Clinical photographs were taken and childhood photographs collected. Eighteen patients (11.5%) were diagnosed with 22q11.2DS, translating into 1 previously unrecognized diagnosis of 22q11.2DS in every 10 adult patients with conotruncal anomalies. While dysmorphic features were detected by our clinical geneticist in all patients, only two-thirds were considered dysmorphic by our cardiologist upon first assessment. Evolution of facial dysmorphic features was noted with age. Extra-cardiac manifestations included velopharyngeal incompetence or cleft palate (44%), hypocalcemia (39%), neurodevelopmental anomalies (33%), thrombocytopenia (28%), psychiatric disorders (17%), epilepsy (17%) and hearing loss (17%). We conclude that under-diagnosis of 22q11.2DS in Chinese adults with conotruncal defects is common and facial dysmorphic features may not be reliably recognized in the setting of adult CHD clinic, referral for genetic evaluation and molecular testing for 22q11.2DS should be offered to patients with conotruncal defects.

Plasma brain natriuretic peptide levels, right ventricular volume overload and exercise capacity in adolescents after surgical repair of tetralogy of Fallot.

BACKGROUND: Right ventricular (RV) volume overload secondary to pulmonary regurgitation contributes to long-term morbidities in patients after tetralogy of Fallot (TOF) repair. We tested the hypothesis that plasma brain natriuretic peptide (BNP) levels relate to RV volume overload, pulmonary regurgitation, and exercise capacity in adolescents after TOF repair. METHODS: We assessed the RV function echocardiographically and plasma BNP levels in 32 postoperative TOF patients aged 14.7+/-3.1 years and 20 age-matched controls. Eighteen patients further underwent cardiovascular magnetic resonance imaging and 26 had exercise testing. RESULTS: Compared with controls, patients had significantly higher BNP levels (p=0.027), greater indexed RV end-diastolic dimension (p<0.001), increased RV myocardial performance index (p=0.005), and reduced tricuspid annular systolic velocity (p=0.008). Multivariate analysis identified indexed RV end-diastolic dimension as the only significant determinant of plasma BNP levels (beta=0.69, p<0.001). Plasma BNP levels correlated positively with indexed RV end-diastolic volume (r=0.6, p=0.009) and pulmonary regurgitant fraction (r=0.54, p=0.026), and negatively with exercise duration (r=-0.45, p=0.021), peak oxygen consumption (r=-0.43, p=0.03), and minute ventilation at maximal exercise (r=-0.52, p=0.006). Multivariate analysis demonstrated BNP levels (beta=-0.43, p=0.034) and body mass index (beta=-0.40, p=0.036) to be independent predictors of peak oxygen consumption. No relations were found between BNP levels and RV myocardial performance index, tricuspid annular velocities and RV ejection fraction. CONCLUSIONS: In adolescent patients after TOF repair, plasma BNP levels relate to RV volume overload, pulmonary regurgitation and exercise capacity.

Chylothorax in children after congenital heart surgery.

BACKGROUND: A definitive management strategy for postoperative chylothorax remains elusive. We reviewed our experience in the management of chylothorax in children after congenital heart surgery. METHODS: The case records of 51 patients, with a median age of 11 months (range, 4 days to 19.6 years), diagnosed to have postoperative chylothorax between 1981 and 2004 were reviewed. The responses of patients to nutritional modifications, octreotide therapy, and surgical interventions were noted. RESULTS: The prevalence of postoperative chylothorax, which developed at a median of 9 days after operation (range, 0 to 24 days), was 0.85% (51 of 5,995). Four patients died, and among the 47 survivors the median duration and total volume of chylous drainage was 15 days (range, 1 to 89 days) and 156 mL/kg (range, 3 to 6,476), respectively. The duration of chyle output was significantly longer after the Fontan-type procedures (p = 0.0006). Twenty-one patients were diagnosed between 1981 and 1999 and managed by nutritional modifications, 2 of whom required further surgical interventions. Of the 30 patients diagnosed between 2000 and 2004, 12 responded to nutritional modifications alone while 18 were started on octreotide therapy at a median of 19.5 days (range, 7 to 35 days) after the onset of chylothorax. Fifteen of the 18 (83%) patients responded to octreotide therapy at 15.3 +/- 5.5 days after starting octreotide, while 3 required further surgical interventions. None developed side effects from octreotide therapy. CONCLUSIONS: Octreotide has been incorporated into the management algorithm of postoperative chylothorax and appears to be a useful adjunctive therapy.

Fate of the unligated vertical vein after repair of supracardiac anomalous pulmonary venous connection.

OBJECTIVE: To determine the fate of the unligated vertical vein after repair of isolated supracardiac total anomalous pulmonary venous connection (TAPVC). METHODS: We reviewed the outcome of 28 patients who were diagnosed to have isolated supracardiac TAPVC and determined the fate of the unligated vertical vein. RESULTS: Of the 28 patients, four died before surgery. The remaining 24 patients underwent surgical correction of TAPVC with (n = 5) or without (n = 19) ligation of vertical vein at a median age of 20 days (range: 1-574 days). There were no significant differences in age, weight, presence of pulmonary venous obstruction, need for preoperative inotropic and ventilatory support, cardiopulmonary bypass duration, postoperative pulmonary hypertensive crisis and requirement of peritoneal dialysis between patients with and those without vertical vein ligation. The in-hospital surgical mortality was 50% (12/24), with 83% (10/12) of deaths occurring before 1990. Patients who died after surgery were significantly younger (median age: 5.5 days vs 37 days, P = 0.005), lighter (3.3 +/- 0.5 kg vs 3.9 +/- 0.6 kg, P = 0.016), more likely to have pulmonary venous obstruction preoperatively (75% vs 12%, P = 0.039) and have undergone surgery before 1990 (83% vs 33%, P = 0.036). The 12 survivors were followed up for a median of 4.7 years (range: 2.3-18.1 years), 10 of whom had their vertical vein unligated. The vertical vein remained patent in five (50%) patients, while stenosis of pulmonary venous anastomosis was only present in one patient. Of these five patients, three had subsequently undergone surgical ligation of the vertical vein to eliminate a large left-to-right shunt. CONCLUSIONS: Patency of the unligated vertical vein is common after the repair of supracardiac TAPVC, even in the absence of pulmonary venous obstruction. The degree of left-to-right shunt through the patent vertical vein may be so significant as to warrant surgical ligation.