Mild hypothermia ameliorates anesthesia toxicity in the neonatal macaque brain.

Sedatives and anesthetics can injure the developing brain. They cause apoptosis of neurons and oligodendrocytes, impair synaptic plasticity, inhibit neurogenesis and trigger long-term neurocognitive deficits. The projected vulnerable period in humans extends from the third trimester of pregnancy to the third year of life. Despite all concerns, there is no ethically and medically acceptable alternative to the use of sedatives and anesthetics for surgeries and painful interventions. Development of measures that prevent injury while allowing the medications to exert their desired actions has enormous translational value. Here we investigated protective potential of hypothermia against histological toxicity of the anesthetic sevoflurane in the developing nonhuman primate brain. Neonatal rhesus monkeys underwent sevoflurane anesthesia over 5 h. Body temperature was regulated in the normothermic (>36.5 °C), mild hypothermic (35-36.5 °C) and moderately hypothermic (<35 °C) range. Animals were euthanized at 8 h and brains examined immunohistochemically (activated caspase 3) and stereologically to quantify apoptotic neuronal and oligodendroglial death. Sevoflurane anesthesia was well tolerated at all temperatures, with oxygen saturations, end tidal CO2 and blood gases remaining at optimal levels. Compared to controls, sevoflurane exposed brains displayed significant apoptosis in gray and white matter affecting neurons and oligodendrocytes. Mild hypothermia (35-36.5 °C) conferred significant protection from apoptotic brain injury, whereas moderate hypothermia (<35 °C) did not. Hypothermia ameliorates anesthesia-induced apoptosis in the neonatal primate brain within a narrow temperature window (35-36.5 °C). Protection is lost at temperatures below 35 °C. Given the mild degree of cooling needed to achieve significant brain protection, application of our findings to humans should be explored further.

Quantitative ultrasound and apoptotic death in the neonatal primate brain.

Apoptosis is triggered in the developing mammalian brain by sedative, anesthetic or antiepileptic drugs during late gestation and early life. Whether human children are vulnerable to this toxicity mechanism remains unknown, as there are no imaging techniques to capture it. Apoptosis is characterized by distinct structural features, which affect the way damaged tissue scatters ultrasound compared to healthy tissue. We evaluated whether apoptosis, triggered by the anesthetic sevoflurane in the brains of neonatal rhesus macaques, can be detected using quantitative ultrasound (QUS). Neonatal (n = 15) rhesus macaques underwent 5 h of sevoflurane anesthesia. QUS images were obtained through the sagittal suture at 0.5 and 6 h. Brains were collected at 8 h and examined immunohistochemically to analyze apoptotic neuronal and oligodendroglial death. Significant apoptosis was detected in white and gray matter throughout the brain, including the thalamus. We measured a change in the effective scatterer size (ESS), a QUS biomarker derived from ultrasound echo signals obtained with clinical scanners, after sevoflurane-anesthesia in the thalamus. Although initial inclusion of all measurements did not reveal a significant correlation, when outliers were excluded, the change in the ESS between the pre- and post-anesthesia measurements correlated strongly and proportionally with the severity of apoptotic death. We report for the first time in vivo changes in QUS parameters, which may reflect severity of apoptosis in the brains of infant nonhuman primates. These findings suggest that QUS may enable in vivo studies of apoptosis in the brains of human infants following exposure to anesthetics, antiepileptics and other brain injury mechanisms.

Cryoablation of atrioventricular nodal reentrant tachycardia in children and adolescents: improved long-term outcomes with increasing experience.

BACKGROUND: Cryoablation is increasingly used for the treatment of atrioventricular nodal reentrant tachycardia (AVNRT). There are limited data regarding its efficacy and late outcomes in the pediatric population. METHODS: We reviewed the clinical records of 70 consecutive pediatric and adolescent patients (mean age: 12.2 ± 3, range: 5-19 years) with AVNRT, with or without additional structural heart disease, who underwent catheter ablation with the intention to use cryoablation as the primary modality between September 2004 and July 2011. RESULTS: The acute success rate was 97.14%. No long-term complications occurred. Patients were followed up for an average time of 46 ± 22.5 months (range 5-90). The recurrence rate was 16%, decreasing from 28% in the first 25 cases to 8.9% in the last 45 cases (p<0.05). Wenckebach point prolongation during cryoapplications was associated with a lower recurrence rate (p<0.05). No other risk factors for recurrence were identified, including persistence of slow pathway conduction. Patients with congenital heart disease had a similar success rate to patients with a structurally normal heart. CONCLUSIONS: When applied to pediatric patients, cryoablation has an excellent success and safety profile, which can improve with increasing experience. Transient Wenckebach point prolongation during cryo-applications may be associated with improved late outcomes.

Preservation of right ventricular structure and function following transatrial-transpulmonary repair of tetralogy of Fallot.

OBJECTIVES: Management strategy of patients with tetralogy of Fallot (TOF)-including timing, as well as surgical technique-remains a controversial topic. We sought to analyse both early and late results of our consistent policy of non-neonatal transatrial/transpulmonary (TA/TP) repair of TOF over almost 14 years, in order to assess preservation or possible deterioration of right ventricular (RV) function. METHODS: All 245 consecutive patients with TOF, referred to our group for repair between September 1997 and December 2010, have been prospectively followed up. Their clinical and echocardiographic data were retrospectively analysed. All underwent complete TA/TP repair at a median age of 1.6 years (range 0.2 to 55.6 years). RESULTS: Follow-up (median 8.5 years, range 0.5 to 14.6 years) was 100% completed. There was no operative death. There were three early re-operations: one for residual right ventricular outflow tract obstruction (RVOTO), one for intractable arrhythmias and one for remote second ventricular septal defect (VSD). There were three non-cardiac-related late deaths. Actuarial survival at 14 years was 98.8% (242/245). Twenty five patients required late re-operation, including 23 patients (9.4%, 23/245) who had pulmonary valve replacement (PVR). All other patients remained asymptomatic at follow-up. Mean residual right ventricular outflow tract (RVOT) pressure gradients have remained stable (6.8 ± 6.6 mmHg, 95% CI 5.9-7.6, early postoperatively, versus 7.6 ± 7.5 mmHg, 95% CI 6.6-8.6 at follow-up; P = 0.015). The mean qualitative grade of pulmonary valve insufficiency (PVI) increased (from 1.4 ± 0.9, 95% CI 1.3-1.5 at discharge to 2.1 ± 1.2, 95% CI 2-2.3 at follow-up; P < 0.001). Similarly, mean qualitative grade of tricuspid valve insufficiency (TVI) also increased (from 1 ± 0.7, 95% CI 0.9-1 at discharge to 1.5 ± 0.8, 95% CI 1.4-1.6 at follow-up; P < 0.001). However, RV function has remained normal in most patients. No significant arrhythmias have been noted. CONCLUSIONS: Our management strategy of non-neonatal TA/TP repair for all patients with TOF is associated with minimal early and late mortality and morbidity, relatively low re-operation rate, preserved RV function and excellent clinical outcomes at follow-up over almost 14 years. Since many patients demonstrated progressive increase in PVI and TVI, a much longer follow-up is necessary to determine the ultimate rates of late re-operation for pulmonary valve replacement (PVR).

The contegra® valved heterograft conduit for right ventricular outflow tract reconstruction: a reliable solution.

INTRODUCTION: The Contegra® bioprosthetic valved conduit, a glutaraldehyde-preserved valve-containing bovine jugular vein graft (Contegra, Medtronic Inc., Minneapolis MN, USA) introduced for clinical trials in 1998, is used for reconstruction of the right ventricular outflow tract (RVOT), mainly in children. This study evaluates our surgical experience with the Contegra® graft, emphasizing the assessment of conduit durability at mid-term follow up. METHODS: The intermediate results of RVOT reconstruction utilizing the Contegra conduit were retrospectively analyzed in a series of 34 consecutive patients (25 male, 9 female), with a mean age of 10.9 ± 11.2 years (range 0.2-46 years). Included were 14 patients with tetralogy of Fallot (TOF) with pulmonary atresia, 11 with reoperation of previously corrected TOF, 5 with truncus arteriosus, 2 with TOF with absent pulmonary valve, 1 reoperation of previously repaired double outlet right ventricle with pulmonary atresia, and 1 undergoing a Ross procedure. Contegra conduit sizes varied in diameter between 12 and 22 mm (mean 18.3 ± 3.2 mm). RESULTS: There were no hospital deaths. There was one early conduit replacement as a result of recurrent thrombosis. Four patients developed early thrombus formation in a valve cusp with complete resolution following anticoagulation therapy. At mean follow up of 85 months (range 6-136 months) and median follow up of 95 months, one patient required Contegra graft explantation in another institution (indications unknown). Freedom from reoperation for Contegra grafts was 94% at 11.4 years. Mean transpulmonary pressure gradients remained low (9.6 ± 5.3 mmHg postoperative, 19.6 ± 10.6 mmHg at follow up). Although there was a clear trend towards worsening of conduit valve insufficiency, this was neither statistically significant nor considered clinically so. CONCLUSIONS: In our experience of 34 consecutive operations, the Contegra® valved conduit for RVOT reconstruction seems to be a reliable alternative to homograft conduits, with promising mid-term freedom from structural deterioration and reoperation.

Radiofrequency ablation of accessory pathways in children and congenital heart disease patients: impact of a nonfluoroscopic navigation system.

BACKGROUND: We sought to assess the impact of routine use of a nonfluoroscopic navigation system in the procedural aspects of radiofrequency ablation of accessory pathways (APs) in pediatric and congenital heart disease (CHD) patients and the reduction of fluoroscopy in different pathway locations. METHODS: This was a retrospective review of 192 patients, divided in two groups: group A (76 patients, fluoroscopic only ablation) and group B (116 patients, combined use of fluoroscopy and a nonfluoroscopic system (NavX™). Comparison of procedural aspects (procedure time, fluoroscopy time, success, complications, and recurrences) was performed. RESULTS: The two groups were comparable in terms of age, AP location, and presence of CHD. The mean age was 11.34 ± 4.65 years in group A versus 10.91 ± 3.68 years in group B. The procedure duration was significantly shorter in group B than in group A (177.06 ± 62.18 vs 242.45 ± 99.07) (P < 0.001). There was a significant reduction in the fluoroscopy time in group B compared to group A (8.27 ± 8.23 vs 39.77 ± 32.65 minutes) (P < 0.001). The difference between the two groups was statistically significant in all categories of APs. The success rate was 97.4% in group A and 96.6% in group B. There were no complications directly related to the use of the nonfluoroscopic system. There was no difference in the recurrence rate. CONCLUSIONS: The use of a nonfluoroscopic system for catheter navigation resulted in significant reduction of total procedure and fluoroscopy time during catheter ablation of APs in pediatric and CHD patients, regardless of the location of the pathway, without a compromise in safety and efficacy.

Impact of age at fontan completion on functional status at mid-term follow up.

INTRODUCTION: Although the Fontan palliation is now being applied to younger patients, the influence of patients' age at the time of surgery on mid- and long-term results remains unclear. It has been our policy to perform Fontan operations when patients are around 5 years old in order to fit a larger conduit and minimize the risk of later obstruction. We sought to investigate whether age at Fontan completion affects subsequent clinical status in patients followed up for more than 3 years. METHODS: We carried out a cross-sectional study of Fontan patients who underwent total cavopulmonary connection between 1997 and 2009 and were followed up for 3 years with detailed chart review, ECG, echocardiogram, and functional status questionnaire. RESULTS: Of the total of 58 patients there were 56 long-term survivors. Of these, 41 had undergone surgery 3 years prior to the time of the study. We were able to contact 37 patients, who comprised our study cohort (mean follow up 6.3, range 3.0-11.0 years). Mean age at operation was 7.4 years (median 5.5, range 3.0-29.5 years). At latest follow up, 97% were in NYHA class I or II. In terms of somatic development, 21% (8/37) for weight and 19% (7/37) for height were below the 25th percentile for age-matched controls. Excluding one patient with developmental delay due to an underlying syndrome, there were 5 patients (13.5%) with mild learning disabilities and one with moderate delays. No additional surgeries had been performed. Tissue Doppler imaging measurements of systolic and diastolic velocities of the lateral annulus of the dominant ventricle revealed abnormalities of both systolic function and diastolic compliance, although qualitatively the systolic function of the single ventricle was considered adequate in all patients. CONCLUSIONS: Although earlier Fontan palliation is considered beneficial in the long term from the viewpoint of exercise capacity and hemodynamics, even late Fontan completion provides acceptable mid-term results in terms of the patients' functional status.

The fontan procedure in Greece: early surgical results and excellent mid-term outcome.

INTRODUCTION: The Fontan operation (modified from its original version) affords excellent palliation for many patients with various forms of anatomic or functional single ventricle. The purpose of this study was to evaluate the outcome of our experience with the Fontan procedure in Greece. METHODS: Fifty-eight consecutive patients with single ventricle physiology had a modified Fontan operation between 1997 and 2009. Their records were reviewed retrospectively. Follow up, which included clinical evaluation and echocardiographic functional assessment, was complete. RESULTS: Median age at operation was 5.7 years (range 3 years to 29.4 years); 46.5% had multistage palliation (stage I and II); 79% had prior bidirectional cavopulmonary shunt (stage II) and 8.6% single stage Fontan. Fifty-four patients had an extracardiac conduit total cavopulmonary connection (EC-TCPC) and 4 an intra-atrial lateral tunnel (LT-TCPC). Fenestration was performed in 26 (44.8%) patients. Operative mortality was 0%. One patient required a short period of extracorporeal membrane oxygenator support. The most frequent complication was prolonged pleural effusion. Median duration of pleural effusion was 17 days (range 6-47 days). Median duration of follow up was 5.44 years (range 0.36 to 11.5 years). There were 2 late deaths (overall mortality 3.4%). One patient died from progressive deterioration of ventricular function within 2 years of operation and the other from fulminant endocarditis. Ten subjects have undergone device closure of a persistent fenestration. All 56 surviving patients are in excellent clinical condition (NYHA class I or II). CONCLUSIONS: We have performed the Fontan procedure over a period of 13 years in Greece with excellent mid- and long-term results. Longer follow up will be necessary to assess the possible incidence of late severe complications, some of which may necessitate heart transplantation.

Atresia of the superior vena cava causing cyanosis and increasing head circumference in an infant.

We report a case of congenital atresia of the superior vena cava (SVC) with stenotic anastomoses between systemic and pulmonary veins, resulting in cyanosis and symptoms consistent with SVC syndrome in an infant.

Surgery for complications of trans-catheter closure of atrial septal defects: a multi-institutional study from the European Congenital Heart Surgeons Association.

OBJECTIVE: This study aims to analyse the collective experience of participating European Congenital Heart Surgeons Association centres in the surgical management of complications resulting from trans-catheter closure of atrial septal defects (ASDs). METHODS: The records of all (n=56) patients, aged 3-70 years (median 18 years), who underwent surgery for complications of trans-catheter ASD closure in 19 participating institutions over a 10-year period (1997-2007) were retrospectively reviewed. Risk factors for surgical complications were sought. Surgical outcomes were compared with those reported for primary surgical ASD closure in the European Association of Cardio-thoracic Surgery Congenital Database. RESULTS: A wide range of ASD sizes (5-34mm) and devices of various types and sizes (range 12-60mm) were involved, including 13 devices less than 20mm. Complications leading to surgery included embolisation (n=29), thrombosis/thrombo-embolism/cerebral ischaemia or stroke (n=12), significant residual shunt (n=12), aortic or atrial perforation or erosion (n=9), haemopericardium with tamponade (n=5), aortic or mitral valve injury (n=2) and endocarditis (n=1). Surgery (39 early emergent and 17 late operations) involved device removal, repair of damaged structures and ASD closure. Late operations were needed 12 days to 8 years (median 3 years) after device implantation. There were three hospital deaths (mortality 5.4%). During the same time period, mortality for all 4453 surgical ASD closures reported in the European Association of Cardio-Thoracic Surgery Congenital Database was 0.36% (p=0.001). CONCLUSIONS: Trans-catheter device closure of ASDs, even in cases when small devices are used, can lead to significant complications requiring surgical intervention. Once a complication leading to surgery occurs, mortality is significantly greater than that of primary surgical ASD closure. Major complications can occur late after device placement. Therefore, lifelong follow-up of patients in whom ASDs have been closed by devices is mandatory.

Emergency transmediastinal pneumonectomy for scimitar syndrome.

Repair of scimitar syndrome presenting in infancy involves either tunneling or reimplantation of the anomalous vein to the left atrium and may be fraught with serious complications such as thrombosis and secondary pulmonary infarction necessitating pneumonectomy. The authors present the case of a severely symptomatic infant with scimitar syndrome, managed initially with closure of an atrial septal defect in the hope of avoiding a repair with considerable risk of scimitar vein thrombosis and pulmonary infarction. Despite initial clinical improvement, subsequent rapid development of spontaneous massive emphysematous degeneration of the right lung necessitated emergency pneumonectomy, which was accomplished via the median sternotomy approach.

Anterior aortic reimplantation of anomalous left coronary artery from the pulmonary artery (ALCAPA) originating from the nonfacing sinus in an adult.

We report successful repair of a rare type of anomalous origin left main coronary artery from the nonfacing pulmonary artery sinus in an adult patient presenting with cardiac arrest as first symptom. Intraoperative findings and surgical technique are discussed.

Etiology and management of chylothorax following pediatric heart surgery.

BACKGROUND: Chylothorax after congenital heart surgery (CHD) is a potentially challenging complication. The purpose of this study was to review our experience with the management of chylothorax following congenital heart surgery. METHODS: Between September 1997 and August 2006, of 1341 pediatric patients undergoing correction of congenital heart disease in our institution, 18 (1.3%) developed chylothorax postoperatively. Surgical procedures included tetralogy of Fallot repair in 10 patients, ventricular septal defect closure (one), atrial septal defect with pulmonary stenosis repair (one), Fontan procedure (three), coarctation of the aorta repair (one), aortopulmonary shunt (one), and ligation of patent ductus arteriosus in one patient. All patients followed a therapeutic protocol including complete drainage of chyle collection and controlled nutrition. Somatostatin was used adjunctively in six (33.3%) patients. Surgical intervention was reserved for persistent lymph leak despite maximal therapy. Following resolution of chylothorax, a medium-chain triglyceride diet was implemented for six weeks. RESULTS: There were no deaths. Fifteen patients (83.3%) responded to conservative therapy. Lymph leak ranged from 2.5 to 14.7 mL/kg per day for 8 to 42 days. Three patients with persistent drainage required thoracotomy with pleurodesis to achieve resolution, in two of which previously attempted chemical pleurodesis with doxycycline proved ineffective. Duration of lymph leak in this subgroup ranged from 15 to 47 days with 5.1 to 7.4 mL/kg per day output. CONCLUSIONS: Postoperative chylothorax is an infrequent complication of surgery for congenital heart disease and can occur even after median sternotomy in the absence of pathologically elevated venous pressure or Fontan circulation. Although hospitalization can be prolonged, conservative therapy is effective in most cases, while surgical pleurodesis proved successful in the refractory cases.

Mid-term results following surgical treatment of congenital cardiac malformations in adults.

The long term consequences of untreated of residual or recurrent lesions pose unique challenges in the growing population of adults with congenitally malformed hearts. In our unit, 335 patients aged from 18 to 72 years, with a mean age of 35 plus or minus 14 years, presented for correction of congenital cardiac disease from September, 1997, through December, 2006. Of the group, 42 (12.5%) had undergone one or more prior surgical procedures, 3 were admitted as emergencies, and a further 10 (3%) had suffered prior cardiac related complications. Symptoms had been noted by 181 patients (54%), and 42 (12.5%) had an established arrhythmia. Chromosomal anomalies were identified in 13 (3.8%), and diagnostic catheterisation was required in 201 (60%) patients. Of the overall group, 2 patients died early (0.6%). Complications occurred in 61 patients (18%), including atrial fibrillation, pneumothorax, postoperative haemorrhage, pericardial or pleural effusions requiring drainage, stroke, complete heart block, endocarditis, wound dehiscence, and peripheral neuropathy. The median length of stay in the intensive care unit and hospital were 2 and 7 days, respectively. Death occurred later in 2 further patients (0.6%), due to atrial fibrillation and pulmonary hypertension. At mean follow-up of 63 plus or minus 30 months, the majority of the remaining patients are well with resolution or significant improvement in their symptoms. Despite the long term deleterious effects of untreated, residual or recurrent congenital cardiac lesions in adults, therefore, we conclude that surgical correction can be achieved with low mortality and acceptable morbidity. Most significant complications are related to arrhythmias.

Nonfluoroscopic catheter navigation for radiofrequency catheter ablation of supraventricular tachycardia in children.

BACKGROUND: Radiofrequency catheter ablation (RCA) of supraventricular tachycardia (SVT) in children is highly successful but requires exposure to radiation. Nonfluoroscopic mapping systems may significantly reduce fluoroscopy time. METHODS: Forty consecutive pediatric patients who underwent RCA for accessory pathways (AP) or AV nodal reentrant tachycardia (AVNRT) with use of a nonfluoroscopic navigation system (Ensite NavX) (group A) were compared retrospectively to 40 consecutive patients with similar diagnoses who underwent RCA with fluoroscopic guidance only (group B). RESULTS: Group A (mean age 12.1+/-2.9 years, mean weight 47+/-13.9 kg) consisted of 11 patients (27.7%) with AVNRT and 29 (72.5%) with AP. Group B (mean age 10.9+/-3.1 years, mean weight 47.1+/-17.1 kg) consisted of 7 patients (17.5%) with AVNRT and 33 (82.5%) with AP. There were no significant differences in AP location, patients with congenital heart disease, and number of radiofrequency lesions. Fluoroscopy time was significantly shorter in group A than in group B (10.4+/-6.1, range 3.1-28.8 minutes, vs 24.9+/-16.0, range 4.4-82.0 minutes, P<0.0001). Procedure duration was also significantly shorter in group A than in group B (170+/-68.5, range 90-420 minutes, vs 218+/-69.3, range 90-360 minutes, P<0.0001). Initial success was 95% in group A and 100% in group B. Tachycardia recurrences occurred in two patients in group A (5%) and six patients in group B (15%). Final success, including repeat ablations for recurrences or failures, was 100% in both groups. CONCLUSIONS: The use of a nonfluoroscopic system for catheter navigation significantly reduced fluoroscopy exposure and total procedure duration of RCA of common SVT substrates in children.