Results of exercise testing at a mean age of 10 years after neonatal arterial switch operation.

AIM: This prospective follow-up study investigated long-term exercise capacity at a mean age of 10 y after neonatal arterial switch operation for transposition of the great arteries in a large group of homogeneous unselected children. METHODS: 56 asymptomatic children, aged 7.9-14.3 y (10.5 +/- 1.6, mean +/- SD), were examined with respect to exercise tolerance, electrocardiographic (ECG) response and activity of biochemical markers for myocardial injury. The protocol included standard electrocardiography, M-mode and two-dimensional echocardiography at rest, a Bruce walking treadmill test to voluntary exhaustion, and determination of cardiac troponin I and T, creatine kinase and myoglobin from venous blood samples at rest and 4 h after exercise. Heart rate, blood-pressure response to exercise stress and endurance time were compared with published results of age-matched normal children. RESULTS: 54 patients (96.4%) had normal exercise capacity; a reduction in 2 patients was not due to cardiac disease. Heart rate and systolic blood pressure rose significantly between rest and peak exercise and did not differ from normal controls, whereas diastolic blood pressure was lower. ECG remained normal at rest and on exercise in 54 children (96.4%). Serum values of cardiac troponin I and T, creatine kinase and myoglobin were normal at rest and after exercise in all patients. CONCLUSION: The study demonstrates excellent long-term exercise capacity after neonatal arterial switch operation. Exercise testing is a useful and non-invasive screening method to detect patients with clinically relevant exercise-induced myocardial ischaemia and should be routinely performed in growing patients.

Long term behavioural outcome after neonatal arterial switch operation for transposition of the great arteries.

AIMS: To evaluate behavioural outcome and quality of life in children aged 8-14 years after neonatal arterial switch operation for transposition of the great arteries. METHODS: Sixty children operated as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass were evaluated at age 7.9-14.3 years by the Child Behaviour Checklist (CBCL) and the Inventory for the Assessment of the Quality of Life in Children and Adolescents (IQCL). RESULTS: Parent reported behavioural outcome on all CBCL problem and competence scores was worse, whereas quality of life on self reported IQCL scores was not reduced compared to the normal population. On multivariate analysis, severe preoperative hypoxia was related to parent reported social problems; peri- and postoperative cardiocirculatory insufficiency was associated with internalizing, externalizing, attention, and total behavioural problems. Reduced expressive language was associated with total behavioural problems, and poor academic achievement was related to parent reported deficits in school performance. Impaired neurological status and reduced endurance capacity both predicted self reported stress by illness. CONCLUSIONS: The neonatal arterial switch operation with combined circulatory arrest and low flow bypass is associated with parent reported long term behavioural impairment, but not with self reported general reduction in quality of life. This discrepancy may be a result of different perception of illness. In our experience, increased risk of long term psychosocial maladjustment after neonatal corrective cardiac surgery is related to the presence of neurological impairment and reduced endurance capacity.

Effect of biologically active coating on biocompatibility of Nitinol devices designed for the closure of intra-atrial communications.

Anti-thrombogenicity and rapid endothelialisation are prerequisites for the use of closure devices of intra-atrial communications in order to reduce the risk of cerebral embolism. The purpose of this study was therefore to assess the effect of bioactive coatings on biocompatibility of Nitinol coils designed for the closure of intra-atrial communications. Nitinol coils (n = 10, each) and flat Nitinol bands (n = 3, each) were treated by basic coating with poly(amino-p-xylylene-co-p-xylylene) and then coated with either heparin, r-hirudin or fibronectin. Anti-thrombogenicity was studied in vitro in a dynamic model with whole blood by partial thromboplastin time (PTT), platelet binding and thrombin generation, respectively, and cytotoxicity by hemolysis. Endothelialisation was studied on Nitinol bands with human umbilical venous endothelial cells (HUVEC) by 3-(4,5-dimethylthiazole-2yl)-2,5-triphenyl tetrazolium (MTT) assay and immnuofluorescence analysis of Ki67, vinculin, fibronectin and von Willebrand Factor. Uncoated or coated devices did not influence hemolysis and PTT. r-Hirudin (but not heparin) and fibronectin coating showed lower platelet binding than uncoated Nitinol (p < 0.005, respectively). Heparin and r-hirudin coating reduced thrombin formation (p < 0.05 versus Nitinol, respectively). HUVEC adhesion, proliferation, and matrix formation decreased in the order: fibronectin coating > uncoated Nitinol > r-hirudin coating > heparin coating > basic coating. MTT assay corroborated these findings. In conclusion, r-hirudin and fibronectin coating, by causing no acute cytotoxicity, decreasing thrombogenicity and increasing endothelialisation improve in vitro biocompatibility of Nitinol devices designed for the closure of intra-atrial communications.

Fate of intramural coronary arteries after arterial switch operation.

BACKGROUND: To evaluate the impact of intramural coronary arteries for the peri-, postoperative and long-term course after arterial switch operation (ASO). METHODS: ASO was performed in 351 patients between 1981 and 2000 with dextrotransposition of the great arteries (d-TGA). Five patients (1.4 %) had an intramural coronary artery. Coronary transfer was performed with a collar under dissection of the commissure without longitudinal splitting of the intramural section. RESULTS: None of these patients died; the intraoperative course was uneventful, and no myocardial ischemic changes were observed. In three patients, follow-up cardiac catheterization after 5, 16 and 53 months revealed an occlusion of the intramural coronary ostium. Exercise electrocardiography and myocardial scintiscan showed myocardial ischemia. Two of these patients underwent a successful internal mammary artery bypass. CONCLUSIONS: The intramural course of coronary arteries in patients with d-TGA is rare and does not cause increased mortality or myocardial infarction rates. However, the risk of coronary occlusion over time seems to be high. Therefore, patients with this condition require selective coronary angiography and frequent exercise investigations. Revascularization with an internal mammary artery bypass may be indicated.

Systemic inflammatory response to cardiac surgery: does female sex really protect?

Sex hormones have important interactions with the immune system and modulate the inflammatory response. In this regard, oestrogen inhibits the transcription of proinflammatory cytokines and confers tissue protection in experimental models. On the basis of this evidence, Trotter et al. in this issue of Critical Care addressed the question of whether, in children, female sex would protect against the deleterious effects of cardiac operations with cardiopulmonary bypass by providing a favourable anti-inflammatory cytokine balance. The observations made in that study suggest sex-related immunomodulation and organ protection during cardiac surgery in the paediatric population. Prospective trials conducted in large series, including sex hormone determination in neonates, infants and children with congenital cardiac defects, are necessary to test this hypothesis. The verification of sex-related intraoperative organ protection would provide new opportunities for preventing the uncontrolled systemic inflammatory response that may occur during cardiac surgery.

Moderate hypothermia during cardiopulmonary bypass reduces myocardial cell damage and myocardial cell death related to cardiac surgery.

OBJECTIVES: The goal of this study was to test the hypothesis that moderate hypothermia during cardiopulmonary bypass (CPB) provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance. BACKGROUND: Moderate hypothermia during experimental CPB stimulates production of interleukin-10 (IL10) and blunts release of tumor necrosis factor-alpha (TNFalpha). METHODS: Twelve young pigs were assigned to a temperature (T degrees ) regimen during CPB: moderate hypothermia (T degrees : 28 degrees C; n = 6) and normothermia (T degrees : 37 degrees C; n = 6). Intra-myocardial TNFalpha- and IL10-messenger RNA were detected by competitive reverse transcriptase polymerase chain reaction and quantification of cytokine synthesis by Western blot. Levels of cardiac troponin I (cTnI) in cardiac lymph and in arterial and coronary venous blood were examined during and after CPB. Myocardial cell damage was assessed by histologic and ultrastructural anomalies of tissue probes taken 6 h after CPB. RESULTS: Synthesis of IL10 was significantly higher, while that of TNFalpha was significantly lower, in pigs that were in moderate hypothermia during surgery than in the others. In contrast with normothermia, moderate hypothermia was also associated with significantly lower cumulative cardiac lymphatic flow during and after CPB, significantly lower lymphatic cTnI concentrations after CPB, significantly lower percentages of myocardial cell necrosis and a significantly lower score of ultrastructural anomalies of myocardial cells. While the percentage of apoptotic cells was not different between groups, the apoptosis/necrosis ratio tended to be higher in animals that were in moderate hypothermia during surgery. In all animals, TNFalpha synthesis correlated positively while IL10 production correlated negatively with necrosis and total cell death, respectively. CONCLUSIONS: Our results suggest that moderate hypothermia during CPB provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance.

Influence of temperature during cardiopulmonary bypass on leukocyte activation, cytokine balance, and post-operative organ damage.

This study examined the hypothesis that core temperature (T(o)) during cardiopulmonary bypass (CPB) influences the perioperative systemic inflammatory response and post-operative organ damage. Twenty-four pigs were assigned to a T(o) regimen during CPB: normothermia (T(o) 37 degrees C; n = 8), moderate hypothermia (T(o) 28 degrees C; n = 8), or deep hypothermia (T(o) 20 degrees C; n = 8). Perioperative leukocyte activation, endotoxin release, and production of tumor necrosis factor-alpha (TNFalpha) and interleukin-10 (IL10) were examined with regard to post-operative organ damage, which was scored at histological examination of tissue probes of heart, lungs, liver, kidney, and ileum, taken 6 h after CPB. Total blood leukocyte count and TNFalpha plasma levels during CPB were significantly lower and IL10 levels were significantly higher in the moderate hypothermic group than in both other groups. Elastase activity, leukotriene B4-, and endotoxin levels were not affected by T(o) regimen. Moderate hypothermia was associated with the lowest histological organ damage score and normothermia with the highest. In all animals organ damage score for heart, lungs, and kidneys correlated significantly with TNFalpha levels at the end of CPB. Our data demonstrate a clear relationship between TNFalpha production during cardiac operations and post-operative multiple-organ damage. Moderate hypothermia, by stimulating IL10 synthesis and suppressing TNFalpha production during CPB, might provide organ protection.

Systemic right ventricular failure after atrial switch operation: midterm results of conversion into an arterial switch.

BACKGROUND: Failure of the systemic right ventricle after atrial switch operation can be treated by conversion into an arterial switch operation. METHODS: Four patients, age 38 to 59 months, presented with right ventricular failure after Senning operation and ventricular septal defect closure. One patient had elevated left ventricular pressure; in the other three patients the left ventricle was retrained to a left ventricular/right ventricular pressure ratio of 0.8 or greater by pulmonary artery banding in 12 to 24 months. RESULTS: Postoperative course after arterial switch operation was prolonged, but clinical condition was good at discharge. Fractional shortening ranged from 20% to 28%. Trace-to-moderate aortic regurgitation was present; only 1 patient had preserved sinus rhythm. After a mean follow-up of 43.5 months 1 patient had died due to left ventricular dysfunction. The survivors are in New York Heart Association functional class I to II. Fractional shortening has improved (29% to 37%); aortic regurgitation has not increased. No patient has undisturbed sinus rhythm. CONCLUSIONS: Conversion of an atrial into an arterial switch is an alternative to cardiac transplantation in childhood. However, the procedure is demanding. Long-term morbidity is caused by rhythm disturbances. Aortic valve performance and left ventricular function require close observation.

Time course of cranial ultrasound abnormalities after arterial switch operation in neonates.

BACKGROUND: The object of this study was to investigate the time course and fate of abnormal findings in cranial ultrasound after performing an arterial switch operation in neonates with transposition of the great arteries, and to analyze the relationship to cerebral cell damage. METHODS: Cranial ultrasound was performed prospectively in 35 neonates with transposition of the great arteries before the operation as well as 4 hours, 1, 2, and 3 days, and 1 and 2 weeks postoperatively. Blood levels of neuron-specific enolase, a marker of cerebral cell damage, were determined before, during, and 4 and 24 hours postoperatively. RESULTS: In 17 of 35 neonates (49%), early postoperative cranial ultrasound revealed abnormalities indistinguishable from intraventricular hemorrhage. In 11 neonates findings were transient and were normalized 2 weeks postoperatively, whereas in the remaining 6 neonates there was evidence of resolving hemorrhage. In all neonates there was a rise in neuron-specific enolase blood concentrations during and 4 hours after extracorporal circulation without correlation to sonographic findings. CONCLUSIONS: Enhanced echogenicity of the choroid plexus or dilatation of the cerebral ventricular system is a frequent early postoperative finding that may be caused by transient plexus edema rather than intraventricular hemorrhage and is not related to cerebral cell damage.

Neurodevelopmental outcome related to cerebral risk factors in children after neonatal arterial switch operation.

BACKGROUND: Neurodevelopmental outcome after neonatal arterial switch operation for complete transposition of the great arteries is an important topic needing prospective assessment. METHODS: A group of 33 unselected children (3.0 to 4.6 years) operated on as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass and a control group of 32 age-matched healthy children (3.0 to 4.8 years) underwent evaluation of socioeconomic and clinical neurological status and a standardized test comprising all areas of child development. Results of patients were related to those of the control group, to population norms, and to preoperative, perioperative, and postoperative cerebral risk factors. RESULTS: Clinical neurological status was normal in 26 patients (78.8%) and reduced in 7 (21.2%). Complete developmental score and the subscores for motor function, visual perception, learning and memory, cognitive function, language, and socioemotional functions were not different compared to population norms. Compared to the patients, the children of the control group scored higher on tests of complete development, cognition, and language, but also on socioeconomic status. Complete developmental score and the scores for motor, cognitive, and language functions were weakly inversely related to the duration of circulatory arrest, but not to the duration of bypass. Cerebral risk factors such as serum levels of the neuron-specific enolase, perinatal acidosis, perinatal asphyxia, peri- and postoperative cardiocirculatory insufficiency, or clinical seizures were not correlated to the test results. CONCLUSIONS: Neonatal arterial switch operation with combined circulatory arrest and low flow bypass is associated with neurological impairment, but not with reduced development as assessed by formal testing of motor, cognitive, language, and behavioral functions. Perioperative serum level of the neuron-specific enolase is not a valid marker for later developmental impairment.

Aortopexy in severe tracheal instability: short-term and long-term outcome in 29 infants and children.

BACKGROUND: Tracheal instability is a hazardous situation after operation for esophageal atresia. In cases with life-threatening apneas, aortopexy is a therapeutic option. To assess efficacy, short-term and long-term outcome was analyzed retrospectively. METHODS: Between 1985 and 2000, 29 patients (age, 1.5 months to 5.2 years) were operated on. A flaccid trachea after operation for esophageal atresia was the cause for life-threatening apneas in 27, and there was external vascular compression in 2 patients. The operative procedure consisted of ventropexy of the aortic arch to the sternum and ventral thoracic wall. RESULTS: There was neither early nor late mortality. A reversible lesion of the phrenic nerve was observed in 2 patients, a pneumothorax in 3, and secondary wound healing in 1. In all but 1 patient symptoms improved markedly or disappeared within days or within the first 3 months postoperatively. An increased susceptibility to respiratory infections was observed in long-term follow-up. CONCLUSIONS: Aortopexy can be performed with no mortality and low morbidity. Aortopexy is effective to prevent further life-threatening apneas, but does not prevent an increased susceptibility to respiratory infections.

25 years after the first arterial switch procedure: mid-term results.

BACKGROUND: 25 years after the first successful arterial switch operation (ASO) for complete transposition of the great arteries (TGA), it is possible to evaluate the mid-term results after this procedure. PATIENTS AND METHODS: From March 1986 through December 1993, 188 patients with TGA underwent ASO (primary in 181 patients and secondary after previous banding of the pulmonary artery in 7 patients). Of the 181 patients with primary ASO, 152 had simple TGA or TGA with a small ventricular septal defect, 90 patients had TGA with a large ventricular septal defect, and 10 had a Taussig-Bing complex. Unselected subgroups of the patients were specifically examined with respect to general health, cognitive and motor development, exercise tolerance and cardiological status. Follow-up time was over 5 years except for the cardiac catheterizations, which were performed one year after ASO. RESULTS: Early mortality was 6.4% in the total group and 5.5% in the 181 patients with primary ASO. 5 patients (2.7%) died late and 5 patients needed reoperation during the follow-up period. Cumulative survival for the whole group was 91% at 5 and 10 years after ASO. 96% of the patients were unlimited in their physical activity, and 99% received no medication. Intelligence was not different from a normal population, but motor and neurological impairment was more frequent (23% and 9%, respectively). The Bruce treadmill test was normal in 47 of 50 patients, but provoked signs of myocardial ischemia or salvos of ventricular tachycardia in 3. ECG and Holter ECG showed normal sinus rhythm in 94.5%, important ventricular ectopy in 2.8% and ischemic changes in 1.4%. Right heart catheterization in 67 patients revealed flattening of the pulmonary trunk and frequently mild or rarely moderate pulmonary artery branch stenosis. Left heart catheterization in 71 patients demonstrated significant enlargement of the aortic annulus and root as well as frequent mild aortic insufficiency. One child had unexpected coronary artery occlusion,and 2 showed a hypoplastic left anterior descending coronary artery. In all patients except one, left ventricular ejection fraction was normal, but 6 patients had regional wall motion abnormalities. CONCLUSION: These results and those of other groups are encouraging, but prospective studies over a much longer follow-up time are necessary before definite conclusions can be drawn.

Anatomical risk factors for mortality and cardiac morbidity after arterial switch operation.

BACKGROUND: The arterial switch operation (ASO) is the treatment of choice for transposition of the great arteries. METHODS: Anatomical risk factors on mortality and morbidity were analyzed retrospectively in 312 patients who underwent ASO between 1982 and 1997. RESULTS: Survival was 95%, 92%, and 92% after 30 days, 5, and 10 years, respectively. Operative survival improved after 1990 to 97% (p < 0.001). Risk factors for operative mortality were complex anatomy (p = 0.018), coronary anomalies (p = 0.008), and prolonged bypass time (p < 0.001). Determinants of late mortality were coronary distribution (p = 0.03), position of the great arteries (p = 0.0095), bypass time (p = 0.047), and aortic coarctation (p = 0.046). After a follow-up of 3.6 +/- 2.7 years (0.1 to 14.9 years), 98% had good left ventricle function, 94% were in sinus rhythm, 2.4% had moderate to severe pulmonary stenosis, 0.3% had significant aortic regurgitation, and 1% had coronary stenosis. Freedom from reoperation was 100%, 96%, and 94% after 1, 5, and 10 years, respectively. No preoperative anatomic parameter correlated with long-term morbidity. CONCLUSIONS: ASO can be performed with low operative mortality (< 5%) and long-term morbidity. Malformations associated with complex transposition of the great arteries influence early and late mortality.

Evaluation of in vivo biocompatibility of different devices for interventional closure of the patent ductus arteriosus in an animal model.

OBJECTIVE: To evaluate the in vivo biocompatibility of three different devices following interventional closure of a patent ductus arteriosus (PDA) in an animal model. MATERIALS AND METHODS: A medical grade stainless steel coil (n = 8), a nickel/titanium coil (n = 10), and a polyvinylalcohol foam plug knitted on a titanium wire frame (n = 11) were used for interventional closure of PDA in a neonatal lamb model. The PDA had been maintained by repetitive angioplasty. Between one and 278 days after implantation the animals were killed and the ductal block removed. In addition to standard histology and scanning electron microscopy, immunohistochemical staining for biocompatibility screening was also undertaken. RESULTS: Electron microscopy revealed the growth of a cellular layer in a cobblestone pattern on the implant surfaces with blood contact, which was completed as early as five weeks after implantation of all devices. Immunohistochemical staining of these superficial cells showed an endothelial cell phenotype. After initial thrombus formation causing occlusion of the PDA after implantation there was ingrowth of fibromuscular cells resembling smooth muscle cells. Transformation of thrombotic material was completed within six weeks in the polyvinylalcohol plug and around the nickel/titanium coil, and within six months after implantation of the stainless steel coil. An implant related foreign body reaction was seen in only one of the stainless steel coil specimens and in two of the nickel/titanium coil specimens. CONCLUSION: After implantation, organisation of thrombotic material with ingrowth of fibromuscular cells was demonstrated in a material dependent time pattern. The time it took for endothelium to cover the implants was independent of the type of implant. Little or no inflammatory reaction of the surrounding tissue was seen nine months after implantation.

Mid-term follow-up after multiple system organ failure following cardiac surgery in children.

Multiple system organ failure after cardiac surgery in children is a severe complication with unknown mid- and long-term sequelae. We therefore evaluated 11 children (aged 20-126 mo, median: 67 mo) having survived multiple system organ failure after cardiac operations for congenital cardiac defects in a cross-sectional follow-up study 12-76 mo (median: 32 mo) after surgery. Clinical and laboratory examinations included cardiac, pulmonary, renal, hepatic, neurological and psychological function tests. All patients had adequate cardiac function. Lung mechanics were abnormal in three children and glomerular renal function was abnormal in two patients. Slight elevation of gamma-glutamyl transpeptidase and coagulation factor deficiency was present in six and seven patients, respectively (five of whom had undergone the Fontan operation). Severe neurological sequelae such as diplegia (n = 1) and mental retardation (n = 1) were observed in two patients. In addition, five children presented delayed motor, graphomotor and/or speech development. Two children were found to have abnormal intelligence. We conclude that with the exception of neurological impairment, mid-term sequelae of multiple system organ failure after cardiac surgery in children are mild. However, longer follow-up using an appropriate control group is mandatory.

Correlations between indices of heart rate variability in healthy children and children with congenital heart disease.

Heart rate variability, as determined from 24-hour Holter recordings, represents a noninvasive parameter for studying the autonomic control of the heart. It decreases with certain disease states characterized by autonomic dysfunction such as congestive heart failure. No study in healthy or cardiac children has been performed to determine the correlations between and within time and frequency domain indices of heart rate variability. We examined five time domain (SDNN, SDNNi, SDANNi, rMSSD and pNN50) and five frequency domain measures (ULF, VLF, LF, HF and balance LF/HF) in 200 healthy children and 200 children with congenital heart disease, aged 3 days to 14 years. All measures were significantly correlated with each other. However, the strength of correlation varied greatly. Our data show that variables strongly dependent on vagal tone (rMSSD, pNN50 and HF) were highly correlated (r value > 0.90), as well as SDNN and SDANNi. We conclude that certain time and frequency domain indices correlate so strongly with each other that they can act as surrogates for each other.

Cardiac myxoma in a 6-year-old child--constitutional symptoms mimicking rheumatic disease and the role of interleukin-6.

A 6-y-old girl with right atrial myxoma presented with remittent fever attacks, general arthralgia and laboratory investigations mimicking rheumatic or autoimmune disease. Interleukin-6 (IL-6) serum concentration was markedly elevated before and normal after tumour resection, whereas myxoma cells stained negatively for IL-6. IL-6 should be considered a myxoma marker: overproduction by myxoma cells and consecutive systemic passage are assumed to cause immunological features.

Coarctation of the left pulmonary artery associated with congenitally corrected transposition.

We describe an infant with congenitally corrected transposition, ventricular septal defect and severe pulmonary stenosis. The heart occupied a midline position. Extension of ductal tissue had resulted in occlusion of the left pulmonary artery. As far as we are aware, this is the first report of an association of coarctation of the left pulmonary artery with corrected transposition.

Experience with an adjustable pulmonary artery banding device in two cases: initial success--midterm failure.

Retraining of the left ventricle in congenitally corrected TGA or after Senning or Mustard operation is necessary when right-ventricular failure is developing and an arterial switch operation is indicated. As these hearts have little tolerance of marginal overbanding, a long-term adjustable pulmonary artery banding device would lower stress and risk of training. Although the inserted device (Osypka) allowed convenient intraoperative pressure ratio adjustment, mid-term adjustment failed due to dysfunction of the system.

Pericardial effusions in infants and children: injection of echo contrast medium enhances the safety of echocardiographically-guided pericardiocentesis.

Pericardiocentesis is usually an easy and uncomplicated procedure when guided by cross-sectional echocardiography, but an abnormal intracardiac or extrapericardial position of the puncture system can occur, especially in children. Injection of echo contrast medium through the puncture needle is a very sensitive, quick, easy and harmless procedure which can be performed at the bedside in all cases in which doubt remains concerning the location of the needle. Prompt enhancement of signal intensity of the pericardial fluid validates the correct intrapericardial position, and permits visualization of the tip of the needle. Absence of echodense formations excludes an intrapericardial position. We recommend the use of echo contrast medium during pericardiocentesis whenever blood is aspirated through the needle, or if there is any doubt concerning its location.