Hyperammonemia and neonatal cardiac failure.

Severe hyperammonemia (hyperNH3) in neonatal cardiac failure after cardiac surgery is rare. We report a case of a 2470-g female infant born at the week 37 of gestation with complex congenital heart disease (truncus arteriosus type III, interrupted aortic arch and tricuspid valve insufficiency) and hemodynamically non-significant intrahepatic arterio-venous malformation. She developed hyperNH3 (highest NH3 blood level: 467 µmol/L) without severe liver failure (INR of 1.9). The origin of the hyperNH3 was multifactorial including limited capacity of liver detoxification function due to congenital porto-caval shunt, liver ischemia, excessive protein intake and increased protein catabolic rate. HyperNH3 treatment partially succeeded in decreasing ammonia level and included discontinuation of protein intake, administration of phenylacetate and sodium benzoate. This case highlights the fact that NH3 detoxification by the liver has limitations for a neonate with multifactorial causes that decrease liver perfusion.

Resetting of the cardiopulmonary baroreflex 10 years after surgical repair of coarctation of the aorta.

OBJECTIVE: To characterise cardiopulmonary baroreflex responses and examine the effects of a 45 minute cycling bout late after successful repair of coarctation of the aorta. SUBJECTS: 10 young adults (mean (SEM) age 18.1 (2.6 years)) operated on for coarctation of the aorta 12.7 (3.5) years earlier, and 10 healthy controls. DESIGN: Forearm blood flow (venous occlusion plethysmography) and vascular resistance, left ventricular internal diastolic diameter, and central venous pressure estimated from an antecubital vein were measured in the supine position at baseline and during five minute applications of lower body negative pressure (LBNP) at -15 mm Hg (LBNP(-15)) and -40 mm Hg (LBNP(-40)). Venous samples were obtained at baseline and during LBNP(-40) for noradrenaline (norepinephrine), adrenaline (epinephrine), renin activity, and aldosterone. The tests were repeated after 45 minutes of moderate exercise. RESULTS: Baseline heart rate (78 (9) v 64 (6) beats/min), echocardiographic cardiac output (6.9 (1.1) v 5.0 (0.2) l/min), shortening fraction (41.7 (1.8)% v 33.3 (1.3)%), and forearm blood flow (3.4 (0.4) v 2.3 (0.3) ml/100 g/min) were higher in the coarctation group than in the controls (p < 0.05). Changes in forearm blood flow and forearm vascular resistance from baseline to LBNP(-40) were similar in both groups, but the relation between forearm vascular resistance and estimated central venous pressure or left ventricular internal diastolic diameter was shifted downward in the coarctation group. Plasma adrenaline was increased in the coarctation group (baseline: 3.2 (0.6) v 2.4 (0.3) pmol/l in controls; LBNP(-40): 687 (151) v 332 (42) pmol/l) (p < 0.05). Both groups showed a similar downward displacement of forearm vascular resistance (p < 0.05) after exercise. CONCLUSIONS: There appears to be resetting of the cardiopulmonary baroreflex to a lower forearm vascular resistance in young adults operated on for coarctation of the aorta, associated with hyperdynamic left ventricular function. Raised circulating adrenaline could contribute to the lower forearm vascular resistance.

[Growth and pubertal development following pediatric heart transplantation]. / Croissance et développement pubertaire après transplantation cardiaque pédiatrique.

STUDY AIM: Prospective study of growth and pubertal development following pediatric heart transplantation in 25 children. PATIENTS AND METHOD: Twenty-five children underwent orthotopic cardiac transplantation at Ste-Justine Hospital from July 1984 to August 1996. Systematic evaluation of anthropometric parameters (weight, height, bone age), hormonal profile (LH, FSH, testosterone, oestradiol, DHEAS), and pubertal development according to Marshall and Tanner were done yearly. RESULTS: Six patients had severe growth retardation at transplantation and only one patient was obese. All patients showed normal height increment following cardiac transplantation. Only 3 patients will not reach genetic target height. The 6 children suffering from congenital cardiomyopathy and showing severe growth delay before surgery did not show any significant catch up growth. Significant weight gain was observed during the first post-operative year (113 +/- 27% ideal body weight p = 0.0002) with evolution towards normal values at 2 years (100 +/- 18%). Thirteen patients were in the prepubertal stage at the time of transplant. Since then, one girl had her menarche at 11 years of age and 3 boys started their pubertal onset at 12 years old. The elevation of blood gonadotrophins during pubertal development correlated with progression of secondary sexual characteristics in both sexes. CONCLUSION: This pediatric population showed normal growth and normal onset and progression of puberty following cardiac transplantation. However, no catch-up growth was observed. The most important factor influencing attainment of maximal growth potential following heart transplantation was the degree of staturoponderal growth retardation at the time of surgery.

Growth and pubertal development following pediatric heart transplantation: a 15-year experience at Ste-Justine Hospital.

BACKGROUND: Thirty-one children and adolescents have undergone allograft heart transplantation at Ste-Justine Hospital from July 1984 to August 1996. Twenty-five patients were followed prospectively more than 3 years to document their growth and pubertal development. METHODS: Parameters surveyed were clinical (height, weight, pubertal staging, and bone age) and biochemical (luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, dehydroepiandrosterone sulphate (DHEAS), IGF-1, and fasting insulin). RESULTS: At surgery, there were 18 boys and 7 girls aged 11 months to 17 years (median 13 years); 14 had congenital heart defects (CHDs) and 11 had a cardiomyopathy (CM). Immunosuppressive therapy included cyclosporine, azathioprine, and prednisone. Eighteen patients were still growing (15 boys, 3 girls): 8 had a retarded bone age and 6 with CHD had severe growth failure. Following surgery, most patients maintained their height within one sodium dodecyl sulfate (SDS) score of that initially observed. Patients reaching their target heights do so mainly in the lower range. Three patients not reaching target height had a CHD. Weight was greatest 1 year postoperatively (113 +/- 27% ideal body weight) with normalization at 2 years (100 +/- 18%). Of the 13 prepubertal patients, menarche occurred at age 12 in 1 girl, while 3 boys began puberty at age 12 years. In both sexes, serum levels of gonadotropins and IGF-1 increased during puberty, moderate hyperinsulinism was observed, and DHEAS levels decreased. CONCLUSIONS: Our results indicate that children and adolescents grow normally following cardiac transplantation and that they attain their target height despite a lack of catch-up growth. They gain weight significantly in the first postoperative year with normalization of their weight at 2 years. Furthermore, the clinical and biochemical indices of puberty are overall within the norms. However, the severity of growth delay at the time of transplantation inherent to the cardiac pathology has a major impact on adult height.

Influence of the postoperative period and surgical procedure on ambulatory blood pressure-determination of hypertension load after successful surgical repair of coarctation of the aorta.

AIMS: This study quantified hypertension load using 24-h ambulatory blood pressure monitoring after successful repair of coarctation of the aorta less than (1) or more than 10 years previously (2) and examined the influence of the surgical procedure (anastomosis or subclavian flap). METHODS AND RESULTS: Ambulatory blood pressure recordings were obtained using an Accutracker II monitor every 30 min during the day and hourly, at night. Day and night systolic and diastolic values were higher in coarctation of the aorta than in controls: (day: systolic blood pressure/diastolic blood pressure: 133/71 +/- 6/4 vs 115/66 +/- 3/2 night: systolic blood pressure/diastolic blood pressure: 117/61 +/- 4/4 vs 107/57 +/- 3/2 mmHg, P < 0.01) and at all times, were higher in coarctation of the aorta (2) than in coarctation of the aorta (1). Clinical daytime systolic hypertension was observed in 20% of recordings from coarctation of the aorta (1) and 49% from coarctation of the aorta (2) while diastolic hypertension was not observed. However, systolic blood pressure and diastolic blood pressure responses to daily activities were significantly higher in coarctation of the aorta than in controls and this was more marked in coarctation of the aorta (2) than in coarctation of the aorta (1). Type of surgery did not affect either hypertension prevalence or blood pressure reactivity. CONCLUSIONS: These observations indicate exaggerated systolic blood pressure and diastolic blood pressure reactivity after repair of coarctation of the aorta, the prevalence of systolic hypertension doubling 10 years after surgery.

Succinyl CoA: 3-oxoacid CoA transferase (SCOT): human cDNA cloning, human chromosomal mapping to 5p13, and mutation detection in a SCOT-deficient patient.

Succinyl CoA: 3-oxoacid CoA transferase (SCOT; E.C.2.8.3.5) mediates the rate-determining step of ketolysis in extrahepatic tissues, the esterification of acetoacetate to CoA for use in energy production. Hereditary SCOT deficiency in humans causes episodes of severe ketoacidosis. We obtained human-heart SCOT cDNA clones spanning the entire 1,560-nt coding sequence. Sequence alignment of the human SCOT peptides with other known CoA transferases revealed several conserved regions of potential functional importance. A single approximately 3.2-kb SCOT mRNA is present in human tissues (heart > leukocytes >> fibroblasts), but no signal is detectable in the human hepatoma cell line HepG2. We mapped the human SCOT locus (OXCT) to the cytogenetic band 5p13 by in situ hybridization. From fibroblasts of a patient with hereditary SCOT deficiency, we amplified and cloned cDNA fragments containing the entire SCOT coding sequence. We found a homozygous C-to-G transversion at nt 848, which changes the Ser 283 codon to a stop codon. This mutation (S283X) is incompatible with normal enzyme function and represents the first documentation of a pathogenic mutation in SCOT deficiency.

[Pubertal development after pediatric heart transplantation]. / Développement pubertaire après la greffe cardiaque pédiatrique.

Twenty-one children and adolescents underwent orthotopic cardiac transplantation at the Hôpital Sainte-Justine between July 1984 and June 1993. Of those patients, 16 (4 girls and 12 boys) who survived more than one year after the procedure were followed prospectively for documentation of onset and progression of puberty. The immunosuppressive therapy included cyclosporine, azathioprine and prednisone. Subjects were evaluated at 6 month intervals for the study of: pubertal development according to staging by the method of Marshall and Tanner and hormonal profile (FSH, LH, testosterone, DHEAS). Despite a stagnation of pubertal signs before surgery, puberty carried on and progressed normally postoperatively. The urinary levels of gonadotropins rose to adequate levels for age. Testosterone levels in boys were related to the progression of secondary sexual characteristics. Levels of DHEAS were drastically reduced, most likely because of the supraphysiological doses of oral glucocorticoids. Our results indicate that after pediatric heart transplantation, puberty progresses normally at adolescence.

[Pulmonary valve replacement in children]. / Remplacement valvulaire pulmonaire chez l'enfant.

From February 1988 to October 1994, 15 pulmonary valve replacements (PVR) have been performed at St-Justine Hospital in children with a mean age of 145.7 months. Ten children previously had a correction of tetralogy of Fallot; two had absent pulmonary valve syndrome; one had been operated on for pulmonary atresia with intact ventricular septum, one other had a correction for a ventricular septal defect with pulmonary artery banding; the last patient developed degeneration of a pulmonary bioprosthesis. The time between the primary repair and the PVR ranged from 61 to 221 months. Fourteen bioprosthesis and one aortic homograft were implanted. All patients had antiplatelet treatment. There was one operative death due to a fatal anaphylactic reaction and one late death occurred unrelated to valvular surgery. At follow-up from 1 to 187 months (mean, 40.7 months) all patients were in New York Heart Association Class 1. No hemorrhagic nor thromboembolic complication have been observed and no reoperation for bioprosthesis failure was necessary. Nevertheless in subsequent echocardiographic studies, two patients with the smallest bioprosthesis (21 mm) have developed pulmonary gradients of 80 and 85 mmHg, 65 and 80 months following PVR. While our results with PVR in children have been satisfactory, this operation should be performed only in symptomatic patients with severe pulmonary regurgitation because of progressive deterioration of the available bioprosthesis.

Peripheral blood flow responses to exercise after successful correction of coarctation of the aorta.

OBJECTIVES: The purpose of this study was to characterize peripheral flow kinetics in response to progressive discontinuous maximal exercise in 10 patients who underwent repair of coarctation of the aorta and 11 age-matched healthy adolescents. BACKGROUND: An impairment of leg blood flow has been suggested on the basis of exaggerated femoral muscle lactate accumulation in patients with successful repair of coarctation. Few data are available describing blood flow kinetics of the exercising leg in such patients. METHODS: Duplex ultrasound provided transcutaneous measurements of peak systolic and end-diastolic flow velocities of the femoral, humeral and renal arteries at rest and immediately after mild, moderate and maximal exercise intensities for computation of mean velocity, resistance index and femoral blood flow. RESULTS: Femoral mean velocity and femoral blood flow increased linearly with exercise intensity in both groups, but the slope of this increase was significantly lower in patients. Similarly, humeral mean velocity increased significantly less in patients than in control subjects. Femoral resistance index sharply decreased from that at rest (patients [mean +/- SE] 1.4 +/- 0.04; control subjects 1.4 +/- 0.03) to mild exercise intensity in both groups (patients 0.69 +/- 0.03; control subjects 0.72 +/- 0.03). A further decrease was observed at maximal exercise in patients (0.60 +/- 0.04, p = 0.08) but not in control subjects (0.69 +/- 0.02). CONCLUSIONS: These observations suggest that despite a greater exercise-induced femoral vasodilation, patients with successful correction of coarctation of the aorta demonstrate an impaired lower limb blood flow in response to strenuous dynamic exercise. In the absence of stenosis at rest, this alteration could result from exaggerated flow turbulence in the descending aorta distal to the site of correction because of loss of elasticity at the site of the resection of the coarcted segment.

Total anomalous pulmonary venous return complicating portoenterostomy for biliary atresia.

Cardiovascular anomalies such as absent inferior vena cava and preduodenal portal vein are reported in cases of biliary atresia and make hepatic portoenterostomy a technical challenge. The authors present the case of a severe cardiac anomaly that significantly altered the functional outcome of a Kasai procedure. Baby M., an 8-week-old boy born with total anomalous pulmonary venous return (TAPVR), underwent hepatic portoenterostomy for biliary atresia. Over the next 3 months he remained icteric and febrile, and failed to gain weight. After multiple antibiotic treatments for suspected cholangitis, he underwent reexploration of the portoenterostomy, with no improvement in his overall condition. His prognosis was considered dismal because correction of the cardiac anomaly is associated with a high mortality rate (> 90%). The cardiac surgeon agreed to attempt a cure of the TAPVR, provided liver transplantation is contemplated if the patient survived. Within 48 hours postoperatively, his hepatic function had improved drastically. He became afebrile, had an improved appetite and weight gain, and was finally discharged 203 days after admission. One year later, he is thriving and remains anicteric. The exact reason for this drastic improvement is not well understood, but the right-sided cardiac failure caused by the TAPVR had a significant effect on the functional outcome of the portoenterostomy.

[Aortic valve replacement in children]. / Remplacement valvulaire aortique chez l'enfant.

From January 1970 to January 1993, 47 aortic valve replacements have been performed in children aged 166.8 +/- 50 months. The valvular pathology was congenital in 39 patients and associated cardiac anomalies were present in 31 cases. 30 children had a previous surgical procedure on the aortic outflow. Seven bioprosthesis and 40 mechanical valves have been implanted. At the time of surgery, an additional major cardiac correction has been performed on 17 occasions (Konno, Bentall, Fontan, correction of truncus arteriosus etc.). While no death occurred in the group subjected only to aortic valve replacement, 7 of the 17 patients where a major cardiac procedure was added died. During a mean follow-up of 61.2 +/- 59.1 months, 3 late deaths occurred, 2 of them non related to valvular surgery. Three reoperations have been performed, in two instances for replacing a degenerated bioprosthesis. One thromboembolic event occurred as well as one temporary episode of haemolytic anaemia. No haemorrhagic complication has been observed. While the results of isolated aortic valve replacement in children are excellent, the risk for hospital death is increased substantially when a major cardiovascular procedure is added to valve replacement, and because of rapid deterioration, the heterografts are now contra-indicated in children.

Survival analysis of infants under age 18 months presenting with tetralogy of Fallot.

The trend to perform early primary repair of tetralogy of Fallot prompted us to review our experience in the current era with the traditional protocol consisting of palliation during infancy, if required, and repair after infancy. During a 10-year period, 270 infants with tetralogy of Fallot presented aged less than 18 months. Thirteen infants (4.8%) had major noncardiac lesions that precluded definitive care for their congenital heart disease. Twenty infants (7.4%) had major associated cardiac lesions (atrioventricular septal defect or absent pulmonary valve syndrome, or both). Survival in this group was poor, with only 58% +/- 12% reaching the age of 10 years. Four of the seven deaths occurred before intracardiac repair was performed. The remaining 237 infants presented with isolated tetralogy of Fallot. Eight-nine percent +/- 2.3% survived to age 10 years. Sixty percent of these infants required palliation, and survival in these infants did not differ from that in those who never required palliation. However, 19 infants (8%) required palliation in the first month of life. In these children, survival to age 10 years was significantly lower (77%), secondary palliation was frequently required (n = 11), and a transannular patch or conduit at the time of repair (10 of 14 patients) was more likely needed than it was in children who had not undergone a palliative procedure during the neonatal period. The survival in infants with tetralogy of Fallot is unlikely to be different, regardless of whether primary repair or a staged repair is carried out. The quality of survival, including the exercise capability and absence of arrhythmias, must be assessed to determine which protocol is superior.

[Critical aortic stenosis in newborn infants. Twenty-five years' experience]. / Sténose aortique critique du nouveau-né. Expérience de vingt-cinq ans.

Operative mortality for critical aortic stenosis in newborn having been reported as high as 20-80%, the percutaneous aortic valvuloplasty is looked upon as an alternative therapy. We elected to review our surgical experience in the last 25 years before changing our therapeutic approach. Among 37 infants included in the study, 28 were boys and 9 girls. Mean age at diagnosis was 14.5 days (1 to 113 days) and decreased to 4.1 days in the last 5 years. Surgery was done at a mean of 37.2 days; 22 infants were operated on before one month of age and 9 in their first week of life. Five died from ventricular fibrillation at incision. Trans-ventricular valvulotomy was attempted in 4 and remaining 28 had trans aortic valvuloplasty. The overall survival of 40% had improved in last five years to 75%. All patients with trans-ventricular approach died and also did the only child with percutaneous angioplasty. Only 13% patients weighing less than 3 kg survived the operation. Follow-up was of 93.3% with a mean time of 66 months. All but one are in NYHA class 1 or 2. Our study identified the following risk factors: preoperative hemodynamic state, surgical weight, associated anomalies of the left ventricle, transventricular valvulotomy and the year of surgery. In view of improved survival, surgery remains a good therapeutic choice.

Hindgut dysgenesis as a cause of constipation with delayed colonic transit.

In a patient complaining of constipation since birth, delayed transit time in the ascending colon was related to a congenital malformation of the hindgut, different from Hirschsprung's disease. This was associated with absence of the left lobe of the liver. There was no propagating electrical muscular activity in the distal bowel.

Acute necrosis of the intestinal mucosa with high serum levels of diamine oxidase.

A patient with acute necrosis of the intestinal mucosa and high serum diamine oxidase activity is described. The 71-year-old woman, with a history of hypertension and cardiovascular and peripheral arteriosclerotic disease, presented with acute epigastric pain, vomiting, and a deteriorating hemodynamic condition. Serum level of the intestinal enzyme diamine oxidase (DAO) obtained on admission, approximately 24 hr after the onset of symptoms, was 7.4 times above the normal value. An exploratory laparotomy performed 6 hr later revealed cyanosis and areas of transmural necrosis involving the entire small bowel. The bowel was not resected because of the extent of lesion. Thirty hours after the first sample was taken and 2 hr before death, the serum DAO level was only slightly above normal. It is suggested that this biochemical marker could provide a valuable tool for the early diagnosis of intestinal ischemia.

Ischemic fecal incontinence and rectal angina.

In 36 patients who consulted for fecal incontinence or rectal pain, or both, there was grossly visible scarring of the rectum and biopsy revealed mucosal atrophy and fibrosis. A steal from the hemorrhoidal arteries to the iliac vessels was demonstrated in 3 subjects. Maximum tolerable volumes within a rectal balloon were smaller than in control subjects, both in men (192 vs. 273 ml) and in women (142 vs. 217 ml) (p less than 0.01). The rectoanal inhibitory reflex was abnormal in all but 1 patient. Specific abnormalities were a decreased amplitude or a prolonged duration of the reflex. It was totally absent in 2 patients. This study is compatible with the hypothesis that chronic ischemia of the rectum may cause fecal incontinence or rectal pain.