Severe Cyanotic Congenital Heart Disease Research Articles

Novel rare genetic variants of familial and sporadic pulmonary atresia identified by whole-exome sequencing.

Pulmonary atresia (PA) is a severe cyanotic congenital heart disease. Although some genetic mutations have been described to be associated with PA, the knowledge of pathogenesis is insufficient. The aim of this research was to use whole-exome sequencing (WES) to determine novel rare genetic variants in PA patients. We performed WES in 33 patients (27 patient-parent trios and 6 single probands) and 300 healthy control individuals. By applying an enhanced analytical framework to incorporate de novo and case-control rare variation, we identified 176 risk genes (100 de novo variants and 87 rare variants). Protein‒protein interaction (PPI) analysis and Genotype-Tissue Expression analysis revealed that 35 putative candidate genes had PPIs with known PA genes with high expression in the human heart. Expression quantitative trait loci analysis revealed that 27 genes that were identified as novel PA genes that could be affected by the surrounding single nucleotide polymorphism were screened. Furthermore, we screened rare damaging variants with a threshold of minor allele frequency at 0.5% in the ExAC_EAS and GnomAD_exome_EAS databases, and the deleteriousness was predicted by bioinformatics tools. For the first time, 18 rare variants in 11 new candidate genes have been identified that may play a role in the pathogenesis of PA. Our research provides new insights into the pathogenesis of PA and helps to identify the critical genes for PA.

A Case of Successful Palliative Care With Peritoneal Dialysis for Severe Cyanotic Congenital Heart Disease

A Case of Successful Palliative Care With Peritoneal Dialysis for Severe Cyanotic Congenital Heart Disease

A case of right sided cardiosplenic heterotaxy syndrome

Heterotaxy is said to exist when the internal thoracoabdominal organs demonstrate abnormal arrangement across the left-right axis of the body. It is categorized into asplenia and polysplenia syndrome variants. Asplenia syndrome is characterized by complex congenital heart defects, asplenia and abdominal heterotaxy. Evidence with regard to the incidence of isomerism is sparse. However, recent studies show that it is commoner in Asians compared to Western populations. Most cases of right isomerism are recognized in early infancy because of the presence of severe forms of complex cyanotic heart disease. Infants with right isomerism invariably have obstruction of the pulmonary outflow tract, as well as common mixing at atria and ventricles, and pulmonary atresia is present in 67% of cases. Here we report an unusual and relatively late presentation of an infant with right sided cardiosplenic heterotaxy syndrome associated with severe cyanotic congenital heart disease.

The Optimum Level of Sevoflurane in Pediatric Echocardiography.

Sevoflurane is shown to be safe and effective in pediatric echocardiography. This study explores the optimum level in pediatric echocardiography. One hundred and twenty children, with an age range of 35days-3years, were included in this study. The children with severe cyanotic congenital heart disease or severe pneumonia, which was Grade I or II according to the American College of Physicians Guideline Grading, were excluded. All children received the anesthesia with sevoflurane. The inhalation anesthesia level decreased from 2.5 to 1.0%, with a decrement of 0.5%. The induction time (T0), echocardiography time (T1), and time to awakening (T2) in each child were recorded, and the changes in the blood pressure, heart rate, breath, and oxygen saturation in each child were also monitored. The Ramsay scale scoring during anesthesia and the case number of failure in echocardiography in each group were also recorded. When the level of sevoflurane inhalation was maintained at 1.0%, the childrens' scores were low, including 8 incompliant children, and p<0.05 in comparison with other groups. The scores increased as the sevoflurane inhalation level increased. When the sevoflurane inhalation increased to 1.5%, the children could sleep with stable blood pressure, and no dysphoria occurred during the echocardiography. When the sevoflurane inhalation level increased to 2.5%, the Ramsay scores did not increase. However, the T2 significantly increased (p<0.05). The blood pressure and heart rate in each group did not change significantly. With the premise of safety and efficacy in children, the optimum level of sevoflurane in pediatric echocardiography was 1.5-2.0%.

Sevoflurane Used for Color Doppler Ultrasound Examination in Children.

The objective of this study is to investigate the feasibility of sevoflurane inhalation in pediatric color doppler ultrasound examination. In this study, 30 cases of children under 1 year were selected. They were all I or II levels according to American Society of Anesthesiology. Children with severe cyanotic congenital heart disease or severe pneumonia were excluded. All the children received anesthesia with sevoflurane. The University of Michigan Sedation Scale was assessed and bispectral index (BIS) was recorded before induction (T0), after induction (T1), when maintaining (T2), and when waking-up (T3). Blood pressure and heart rate were monitored during the color doppler ultrasound examination, the time to receive sedation examination and anesthesia recovery time were also recorded. (1) Score for UMSS was zero at T0 and 3 at T1; (2) BIS value was 93.18 ± 2.94 at T0 and decreased to 87.6 ± 3.9 at T1; (3) Blood pressure or heart rate did not decline obviously; (4) The time to receive sedation examination was 46.4 ± 13.1 s and anesthesia recovery time was 7.8 ± 5.3 min. In conclusion, sevoflurane can be used in pediatric color doppler ultrasound examination safely and effectively.

Executive Function in Children and Adolescents with Critical Cyanotic Congenital Heart Disease.

Children and adolescents with critical cyanotic congenital heart disease (CHD) are at risk for deficits in aspects of executive function (EF). The primary aim of this investigation was to compare EF outcomes in three groups of children/adolescents with severe CHD and controls (ages 10-19 years). Participants included 463 children/adolescents with CHD [dextro-transposition of the great arteries (TGA), n=139; tetralogy of Fallot (TOF), n=68; and, single-ventricle anatomy requiring Fontan procedure (SVF), n=145] and 111 controls, who underwent laboratory and informant-based evaluation of EF skills. Rates of EF impairment on D-KEFS measures were nearly twice as high for CHD groups (75-81%) than controls (43%). Distinct EF profiles were documented between CHD groups on D-KEFS tasks. Deficits in flexibility/problem-solving and verbally mediated EF skills were documented in all three CHD groups; visuo-spatially mediated EF abilities were impaired in TOF and SVF groups, but preserved in TGA. Parent, teacher, and self-report ratings on the BRIEF highlighted unique patterns of metacognitive and self-regulatory concerns across informants. CHD poses a serious threat to EF development. Greater severity of CHD is associated with worse EF outcomes. With increased understanding of the cognitive and self-regulatory vulnerabilities experienced by children and adolescents with CHD, it may be possible to identify risks early and provide individualized supports to promote optimal neurodevelopment.

Intentional use of intra‐arterial medications when venous access is not available

The difficult or impossible establishment of venous access is occasionally encountered in the pediatric population, especially in patients exposed to repeated surgical procedures or those with underlying comorbid features. Potential options in such situations include the intramuscular, intraosseous (IO), and intratracheal administration of medications. Although IO access is accepted as the route of choice in emergency situations, its use is not universally accepted in the operating room setting when the administration of medications is nonemergent. We report the intentional and elective use of the intra-arterial (IA) administration of vecuronium, atropine, fentanyl, and fluid during the provision of anesthesia for two infants with severe cyanotic congenital heart disease in whom venous access could not readily be obtained. The potential role of IA administration of medications is discussed and previous reports from the literature are reviewed.

Delayed primary anastomosis for wide-defect esophageal atresia: a 17-year experience

Fifteen infants with wide-defect esophageal atresia treated by delayed primary anastomosis since 1975 were reviewed. Nine had an associated tracheoesophageal fistula: 6 lower-pouch.and 3 upper-pouch. All underwent initial gastrostomy and division of a lower-pouch fistula when present. Anastomosis was achieved in all cases at 18–252 days, but with circular myotomy in 4 and upper-pouch elongation in 4. Two had anastomotic leaks and 2 had chylothorax, which all healed with conservative management. Fourteen have needed esophageal dilatation and 2 have had anastomotic strictures resected. One developed an upper-pouch diverticulum, which has been resected. Five had symptomatic gastroesophageal reflux, 2 of whom have had fundoplication. One died from associated severe cyanotic congenital heart disease at the age of 12 months. The 14 survivors are well and making good progress. Delayed primary anastomosis remains our preferred approach for all infants with wide-defect esophageal atresia.

Β-Adrenoceptor density on mononuclear leukocytes and right atrial myocardium in infants and children with congenital heart disease

Sympathetic regulation of myocardial performance has been shown to be altered in congestive heart failure. Right atrial tissue of children with severe acyanotic and cyanotic congenital heart disease (CHD) showed a significantly lower beta-receptor density than that of children with less severe defects. Since mononuclear leukocytes (MNL) contain a homogeneous population of beta 2-adrenoceptors which have similar properties to those of cardiac beta 2-adrenoceptors, they are frequently used for studying the beta-adrenergic system. In a group of 37 children with CHD of different types and severity who underwent cardiac surgery, we compared the MNL beta-adrenoceptor density to the type and severity of CHD and looked for a possible relationship to plasma catecholamine levels and to the right atrial beta-adrenoceptor density. Membranes of MNL and myocardial cells were radiolabeled with (-)3-[125I]Iodocyanopindolol [( 125I]ICYP). A significantly higher beta-adrenoceptor density on MNL was found in patients with moderate acyanotic CHD (group I) than in those with severe acyanotic (group II) and cyanotic CHD (group III). Patients of group I showed approximately 50% higher myocardial beta-receptor density than those of groups II and III. ICI 118.551-[125I]ICYP competition studies revealed that in groups II and III significantly lower proportions and densities of beta 1-receptors were found compared to group I. Noradrenaline (NA) plasma levels in group II and group III were significantly higher than those in group I. The adrenaline plasma levels were found to be very high in all children with CHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Rhabdomyoma in a Newborn. Two-Dimensional Echocardiographic Diagnosis.

Primary cardiac tumors are quite rare in the newborn period. Prior to surgery, cardiac catheterization and angiocardiography have been performed to confirm the two-dimensional echocardiographic findings. In this report a 2-day-old baby with the clinical impression of severe cyanotic congenital heart disease diagnosed by two-dimensional echocardiography as multiple rhabdomyoma and confirmed by surgery is presented. It is emphasized that two-dimensional echocardiography is a very useful technique for the diagnosis of primary cardiac tumors. By means of this method severely symptomatic newborns may be taken directly to surgery without prior cardiac catheterization, thus minimizing complications.

Palliative Surgery for Cyanotic Congenital Heart Disease

Recently, there has been an increasing emphasis on definitive correction of congenital heart defects at an early age. Nevertheless, in the presence of severe cyanotic congenital heart disease, survival may depend on palliative techniques designed either (1) to promote increased pulmonary blood flow by means of a systemic-pulmonary artery shunt or (2) to promote mixing of blood by means of a left-to-right shunt. For some patients with other cases, palliative techniques serve to "buy time" until the patient attains a more desirable age and body size. Whether subsequent definitive repair is performed, the above-described procedures allow the salvage of numerous patients whose cyanotic anomalies would otherwise be incompatible with life.

Cardiovascular effects of d-tubocurarine and pancuronium in newborn lambs during normoxia and hypoxia.

Nondepolarizing muscle relaxants are administered to hypoxic neonates (including those with severe cyanotic congenital heart disease) to reduce oxygen consumption. However, it is unknown whether paralysis actually reduces oxygen consumption or whether the drugs used affect the cardiovascular system of neonates. Therefore, we studied the effects of d-tubocurarine and pancuronium induced muscle paralysis on oxygen consumption, cardiac output, and tissue oxygen delivery in healthy normoxic and hypoxic 1- to 3-day-old lambs. We measured intravascular pressures, cardiac output and its distribution (microspheres), and blood gases and pH during: 1) spontaneous respiration with room air (control); 2) spontaneous respiration with a Pao2 of 27-33 mm Hg (hypoxia); 3) mechanical ventilation with room air; 4) mechanical ventilation with room air and paralysis with d-tubocurarine (0.3 mg/kg) or pancuronium (0.1 mg/kg); and 5) mechanical ventilation with hypoxia and paralysis. Mechanical ventilation, with or without muscle paralysis, had no effect on the oxygen delivery or oxygen consumption of normoxic animals. Hypoxia and spontaneous ventilation had no effect on oxygen consumption, but hypoxia, paralysis, and mechanical ventilation reduced it 35% (p less than 0.002 d-tubocurarine) and 50% (p less than 0.001 pancuronium). Cardiac output was unaffected by oxygenation, mechanical ventilation, or muscle paralysis. However, blood flow to the brain and heart increased during hypoxia, which maintained normal oxygen delivery to these organs. During hypoxia and spontaneous ventilation, mean pulmonary arterial pressures increased 34% (d-tubocurarine) and 54% (pancuronium) above control; during hypoxia, muscle paralysis, and mechanical ventilation, it increased 81%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute myocardial infarction secondary to polycythaemia in a case of cyanotic congenital heart disease

A case of coronary thrombosis resulting from secondary polycythaemia due to severe cyanotic congenital heart disease in a young girl of 19 years of age is described. This resulted in a fatal myocardial infarction. There was no evidence of coronary atheroma.

169 NON-INVASIVE DETERMINATION OF ARTERIAL OXYGEN SATURATION IN CYANOTIC CONGENITAL HEART DISEASE

We evaluated non-invasive transcutaneous pulse oximetry (NIPO) in 28 pediatric pts, ages 3 mos.-11 yrs, wts. 2.5-36 kgs. with moderate to severe cyanotic congenital heart disease (CyCHD) during cardiac catheterization, intra-operatively during closed heart surgery and in the ICU. O2 saturations (sats) from (NIPO), using the Nellcor Pulse Oximeter #100, were compared with simultaneously obtained arterial blood samples analyzed by the IL282 CO-oximeter. Comparison of 94 data pairs showed excellent agreement between the 2 methods over a wide range of O2 sats (38-90%) with r=.93 SEE 3.62. Even in the low range of O2 sats (38-75%) 34 data pairs showed good agreement between the 2 methods, r=.81 SEE 5.14. The accuracy of the NIPO was independent of the pts wt., heart rate or blood pressure. In 3 pts, the sharp decrease in O2 sats allowed the diagnosis of hypoxic tetralogy spells before the onset of any clinical findings. Intra-operatively the use of NIPO confirmed the patency of aorto-pulmonary shunts and changes in arterial O2 sats accompanying general anesthesia. Post operatively in the ICU, NIPO allowed accurate management of ventilatory support during varying hemodynamic states. Thus, in children with CyCHD, NIPO is an accurate method of determining O2 sats and contributes to improved management during cardiac catheterization, heart surgery and recovery in the ICU. This study establishes a new application of NIPO in the care of children with CyCHD.

Glucose homeostasis in children with severe cyanotic congenital heart disease

Six children with severe forms of cyanotic congenital heart disease underwent a series of challenge studies in an attempt to clarify the pathophysiology of the hypoglycemia observed in these disorders. The glycemic response to intravenous glucagon positively correlated with the fasting glucose concentration (P<0.01). Following a 26-to 30-hour fast, two of six CCHD children developed hypoglycemia in the absence of significant differences in ketone body, alanine, or insulin concentrations when compared with controls. Blood lactate (P<0.05), pyruvate (P<0.02), plasma glucagon (P<0.05), and cortisol (P<0.01) values were increased at the end of the fast when compared to those in normal fasting children. Intravenous alanine challenge at the end of the fast demonstrated normal glycemic responses in all subjects, regardless of initial plasma glucose or lactate concentrations. One subject had an abnormal rise in lactate and β-hydroxybutyrate following alanine administration. Glucose and alanine turnover studies utilizing stable isotopes revealed normal glucose kinetics but lower alanine flux (8.4±1.1 μmol/kg·min vs 12.3±1.15 μmol/kg/min, P<0.05) and metabolic clearance rates (28.0±3.5 vs 51.0±7.4 ml/kg·min) in the CCHD subjects when compared to normal children. We conclude that hepatic glycogenolytic and glyconeogenic enzyme mechanisms are intact in patients with CCHD. The hypoglycemia is associated with glycogen depletion but not with abnormal secretion of glycoregulatory hormones. The decreased alanine metabolic clearance rate and the increased fasting lactate and pyruvate concentrations may reflect decreased hepatic uptake of these potential gluconeogenic substrates, leading to a functional defect in hepatic gluconeogenesis. These abnormalities may be secondary to decreased hepatic perfusion, but other mechanisms cannot be directly excluded. Six children with severe forms of cyanotic congenital heart disease underwent a series of challenge studies in an attempt to clarify the pathophysiology of the hypoglycemia observed in these disorders. The glycemic response to intravenous glucagon positively correlated with the fasting glucose concentration (P<0.01). Following a 26-to 30-hour fast, two of six CCHD children developed hypoglycemia in the absence of significant differences in ketone body, alanine, or insulin concentrations when compared with controls. Blood lactate (P<0.05), pyruvate (P<0.02), plasma glucagon (P<0.05), and cortisol (P<0.01) values were increased at the end of the fast when compared to those in normal fasting children. Intravenous alanine challenge at the end of the fast demonstrated normal glycemic responses in all subjects, regardless of initial plasma glucose or lactate concentrations. One subject had an abnormal rise in lactate and β-hydroxybutyrate following alanine administration. Glucose and alanine turnover studies utilizing stable isotopes revealed normal glucose kinetics but lower alanine flux (8.4±1.1 μmol/kg·min vs 12.3±1.15 μmol/kg/min, P<0.05) and metabolic clearance rates (28.0±3.5 vs 51.0±7.4 ml/kg·min) in the CCHD subjects when compared to normal children. We conclude that hepatic glycogenolytic and glyconeogenic enzyme mechanisms are intact in patients with CCHD. The hypoglycemia is associated with glycogen depletion but not with abnormal secretion of glycoregulatory hormones. The decreased alanine metabolic clearance rate and the increased fasting lactate and pyruvate concentrations may reflect decreased hepatic uptake of these potential gluconeogenic substrates, leading to a functional defect in hepatic gluconeogenesis. These abnormalities may be secondary to decreased hepatic perfusion, but other mechanisms cannot be directly excluded.

Congenital Levojuxtaposition of the Right Atrial Appendage: Association with Persistent Truncus Arteriosus, Type 4

Congenital levojuxtaposition of the right atrial appendage is a rare malformation most commonly associated with a transposition of the great arteries. We report a case of levojuxtaposition of the right atrial appendage associated with a persistant truncus arteriosus, type 4. Juxtaposition of the atrial appendage is a sign of severe cyanotic congenital heart disease, and this is best diagnosed by a selective right atriogram or superior venacavogram.

Correction of platelet dysfunction and bleeding in cyanotic congenital heart disease by simple red cell volume reduction

Red cell volume reduction corrected the platelet aggregation abnormality and bleeding tendency in four boys, aged 5 to 16 years, with severe cyanotic congenital heart disease and polycythemia. Red cell volume was reduced by replacing 15 to 20 ml/kg body weight of the patient's blood with plasma in 50 ml increments over a 1 to 2 hour period. Within 3 days, platelet aggregation was restored essentially to normal, and previous bleeding symptoms disappeared. Platelet aggregation remained normal during 3 weeks of follow-up study and hematocrit values remained at palliative levels. The procedure was safe and simple, and it had beneficial effects not only on bleeding but also on other symptoms related to polycythemia. These preliminary observations suggest that red cell volume reduction may be useful preoperatively in patients with cyanotic heart disease and defects in platelet function to lessen the risk of serious bleeding during the early postoperative period. Palliation in severely cyanotic children whose condition is inoperable is another possible indication for this procedure.

CORRECTION OF PLATELET DYSFUNCTION AND BLEEDING IN CYANOTIC CONGENITAL HEART DISEASE BY SIMPLE RED CELL VOLUME REDUCTION

Red cell volume reduction corrected the platelet aggregation abnormality and bleeding tendency exhibited by 4 boys, ages 5 to 16, with severe cyanotic congenital heart disease and polycythemia (Hcts 68-75%). Red cell volume was lowered by replacing 15 to 20 ml/Kg of the patient's blood with plasma in 50 ml increments over a 1 to 2 hour period. Within 3 days, platelet aggregation was restored to normal, and previous bleeding symptoms disappeared. Platelet aggregation remained normal during 3 weeks of follow-up while hematocrits remained at palliative levels. The procedure was safe, simple, and produced beneficial effects not only on bleeding, but, also on other symptoms related to polycythemia and high blood viscosity.The mechanism by which platelet function is corrected is not yet understood. In vitro studies showed no corrective effects of donor plasma on the abnormal platelets.For polycythemic patients with cyanotic heart disease and platelet defects who require surgery, red cell volume reduction is recommended preoperatively to lessen the risk of serious bleeding during the early postoperative period. Palliation of severely cyanotic children who are inoperable is another indication for this procedure.

Macroaggregated RISA lung scan in congenital heart disease.

Macroaggregated RISA lung scans in 60 children with various congenital heart diseases were correlated with abnormal patterns of certain specific types of abnormality. Renal activity in patients with right-to-left cardiovascular shunts and its amount could be used as an index to shunt magnitude. Scans following surgery helped evaluate its effectiveness. Patency of a sub-clavian-pulmonary anastomosis was verified by demonstrating diminished activity in the lung on the side of the shunt and in the kidneys. In severe cyanotic congenital heart disease, the lung scan served as an additional guide when findings suggestive of thrombosis were observed.

Technique and preliminary results of selective catheterization of patients with Blalock-Taussig shunts.

A technique for retrograde catheterization of the pulmonary artery through patent Blalock-Taussig shunts is described. Pulmonary artery pressure and oxygen saturation are determined and pulmonary angiography is performed via this catheter. The angiographic anatomy of the main pulmonary artery and its branches was demonstrated better by this technique than by conventional right ventriculography in 11 patients with severe cyanotic congenital heart disease.