Intermediate monocytes exhibit higher levels of TLR2, TLR4 and CD64 early after congenital heart surgery.

INTRODUCTION: Congenital heart surgery with cardiopulmonary bypass (CPB) initiates an immune response which frequently leads to organ dysfunction and a systemic inflammatory response. Complications associated with exacerbated immune responses may severely impact the postoperative recovery. The objective was to describe the characteristics of monocyte subpopulations and neutrophils at the level of pattern recognition receptors (PRR) and the cytokine response after CPB in infants. METHODS: An observational cohort study was conducted between June 2016 and June 2017 of infants < 2 years of age, electively admitted for surgical correction of acyanotic congenital heart defects using CPB. Fourteen blood samples were collected sequentially and processed immediately during and up to 48 h following cardiac surgery for each patient. Flow cytometry analysis comprised monocytic and granulocytic surface expression of CD14, CD16, CD64, TLR2, TLR4 and Dectin-1 (CLEC7A). Monocyte subpopulations were further defined as classical (CD14++/CD16-), intermediate (CD14++/CD16+) and nonclassical (CD14+/CD16++) monocytes. Plasma concentrations of 14 cytokines, including G-CSF, GM-CSF, IL-1ß, IL-1RA, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, TNF-α, IFN-γ, MIP-1ß (CCL4) and TGF-ß1, were measured using multiplex immunoassay for seven points in time. RESULTS: Samples from 21 infants (median age 7.4 months) were analyzed by flow cytometry and from 11 infants, cytokine concentrations were measured. Classical and intermediate monocytes showed first receptor upregulation with an increase in CD64 expression four hours post CPB. CD64-expression on intermediate monocytes almost tripled 48 h post CPB (p < 0.0001). TLR4 was only increased on intermediate monocytes, occurring 12 h post CPB (p = 0.0406) along with elevated TLR2 levels (p = 0.0002). TLR4 expression on intermediate monocytes correlated with vasoactive-inotropic score (rs = 0.642, p = 0.0017), duration of ventilation (rs = 0.485, p = 0.0259), highest serum creatinine (rs = 0.547, p = 0.0102), postsurgical transfusion (total volume per kg bodyweight) (rs = 0.469, p = 0.0321) and lowest mean arterial pressure (rs = -0.530, p = 0.0135). Concentrations of IL-10, MIP-1ß, IL-8, G-CSF and IL-6 increased one hour post CPB. Methylprednisolone administration in six patients had no significant influence on the studied surface receptors but led to lower IL-8 and higher IL-10 plasma concentrations. CONCLUSIONS: Congenital heart surgery with CPB induces a systemic inflammatory process including cytokine response and changes in PRR expression. Intermediate monocytes feature specific inflammatory characteristics in the 48 h after pediatric CPB and TLR4 correlates with poorer clinical course, which might provide a potential diagnostic or even therapeutic target.

A Wide Comparison of Techniques for Repair of PAPVCs: One Institution's 20-Year Experience.

BACKGROUND: Different methods for surgical correction of partial anomalous pulmonary venous connection (PAPVC) exist. We evaluated the outcomes of four techniques regarding morbidity and mortality. METHODS: A total of 116 patients underwent PAPVC repair in our institution over a period of 20 years. Single-patch technique (n = 82 [71%], mean age: 18.59 ± 20.49 years), double-patch technique (n = 13 [11%], mean age: 43.18 ± 25.14 years), Warden's technique (n = 7 [6%], mean age: 10.04 ± 10.47 years), and direct implantation of anomalous pulmonary veins (n = 14 [12%], mean age: 14.42 ± 18.58 years) were examined. RESULTS: Out of the 116 patients, one patient (0.9%) developed pulmonary hypertension after discharge and three patients (2.6%) with normal right cardiac function showed right ventricular failure. In total, a pacemaker was inserted in seven cases (6%). Three patients (2.6%) presented with persistent nonsinus rhythm during follow-up. This complication was most frequently seen in the double-patch group being significantly increased compared with the other groups (p = 0.035). One patient presented with a mild stenosis of the superior vena cava. There were two early, nonsurgery-related deaths and no late mortality. CONCLUSION: Operative therapy of PAPVC has low postoperative morbidity and mortality. Therefore, surgical repair of this cardiac anomaly is a safe and reproducible treatment independent of the applied method. The surgical technique must be selected based on the anatomy and possible accompanying congenital heart defects. Special care should be taken when using the double-patch technique because of significant more frequent nonsinus rhythm events postoperatively.

Depth of anesthesia by Narcotrend® and postoperative characteristics in children undergoing cardiac surgery under extracorporeal circulation: a retrospective comparison of two anesthetic regimens.

BACKGROUND: Depth of anesthesia may be insufficient in pediatric cardiac anesthesia if a total intravenous anesthetic regimen with opioids and midazolam is used during cardiopulmonary bypass. The advantages of sevoflurane-based balanced anesthesia may be (1) a more graduated regulation of the depth of anesthesia during cardiopulmonary bypass and (2) a reduction in postoperative ventilation time for children in comparison with total intravenous anesthesia. AIM: To evaluate a possibly positive effect of sevoflurane-based balanced anesthesia in children undergoing cardiac surgery we analyzed whether this anesthetic regimen had a significant effect related to (1) depth of anesthesia, (2) the need for opioids during cardiopulmonary bypass as well as on postoperative characteristics such as (3) time of postoperative ventilation, and (4) duration of stay in the intensive care unit in comparison with total intravenous anesthesia. METHODS: In a retrospective analysis, data from heart-lung machine protocols from 2013 to 2016 were compared according to anesthetic regimen (sevoflurane-balanced anesthesia, n = 70 vs. total intravenous anesthesia, n = 65). Children (age: 8 weeks to 14 years) undergoing cardiac surgery with cardiopulmonary bypass were included. As a primary outcome measure, we compared Narcotrend® system-extracted data to detect insufficient phases of anesthetic depth during extracorporeal circulation under moderate hypothermia. Postoperatively, we measured the postoperative ventilation time and the number of days in the intensive care unit. Furthermore, we analyzed patients' specific characteristics such as opioid consumption during cardiopulmonary bypass. Regression analysis relating primary objectives was done using the following variables: anesthetic regimen, age, severity of illness/surgery, and cumulative dosage of opiates during cardiopulmonary bypass. RESULTS: No significant differences were observed in descriptive patient characteristics (age, body weight, height, and body temperature) between the two groups. Further, no significant differences were found in depth of anesthesia by analyzing phases of superficial B1-C2-electroencephalography Narcotrend® data. No marked difference between the groups was observed for the duration of postoperative intensive care unit stay. However, the postoperative ventilation time (median (95% CI, hours)) was significantly lower in the sevoflurane-based balanced anesthesia group (6.0 (2.0-15.0)) than in the total intravenous anesthesia group (13.5 (7.0-25)). A higher dosage of opioids and midazolam was required in the total intravenous anesthesia group to maintain adequate anesthesia during cardiopulmonary bypass. Regression analysis showed an additional, significant impact of the following factors: severity of illness and severity grade of cardiac surgery (according to Aristotle) on the primary endpoint. CONCLUSION: In children undergoing cardiac surgery in our department, the use of sevoflurane-balanced anesthesia during cardiopulmonary bypass showed no superiority of inhalational agents over total intravenous anesthesia with opioids and benzodiazepines preventing phases of superficial anesthesia, but a marked advantage for the postoperative ventilation time compared with total intravenous anesthesia.

Assessment of Suspected Vascular Rings and Slings and/or Airway Pathologies Using Magnetic Resonance Imaging Rather Than Computed Tomography.

BACKGROUND: Congenital cardiovascular malformations (CCVM) may cause infrequently airway pathologies (AP) in children and are of prognostic and therapeutic relevance. While computed tomography (CT) is considered first-line imaging modality in many centres, we started using magnetic resonance imaging (MRI) more and more in the last years to detect CCVM and AP to avoid radiation in this patient group. OBJECTIVE: The aim of this retrospective study was to determine and to compare the diagnostic accuracy of CT and MRI when used to detect CCVM and/or AP. METHODS: All patients suspected to have CCVM and/or AP and examined either by CT or MRI between 2000 and 2013 in our hospital were included. Extension and type of CCVM, as well as their relationship to esophagus, trachea or bronchi were assessed and related to findings of tracheobronchoscopy, cardiac catheterization or surgery if available. RESULTS: One hundred six patients (median [range] 4 years [2 days to 66 years]) were examined by CT (n = 27) or MRI (n = 79). In 78 patients (74%), CCVM and/or AP were found with either of the imaging methods. CCVM were found in 63 subjects. Forty-six of 63 subjects had both, CCVM and AP. The presence of CCVM was always detected correctly by CT or MRI, although both techniques had a weakness detecting atretic segments directly. AP (n = 61) were correctly diagnosed in all patients not intubated for artificial ventilation by CT (n = 17) and in all but 2 patients by MRI (39 out of 41). CONCLUSIONS: MRI is sensitive to detect CCVM associated with AP equally to CT without any radiation exposure.

Aortic Coarctation a Systemic Vessel Disease-Insights from Magnetic Resonance Imaging.

BACKGROUND: Even after successful aortic coarctation (CoA) repair, hypertension causes premature morbidity and mortality. The mechanisms are not clear. The aim was to evaluate elastic wall properties and aortic morphology and to correlate these results with severity of restenosis, hypertension, aortic arch geometry, noninvasive pressure gradients, and time and kind of surgical procedure. METHODS: Eighty-nine patients (17 ± 6.3 years) and 20 controls (18 ± 4.9 years) were examined using magnetic resonance imaging (MRI). In addition to contrast-enhanced MR angiography and flow measurements, CINE MRI was performed to assess the relative change of aortic cross-sectional areas at diaphragm level to calculate aortic compliance (C). RESULTS: Fifty-four percent of all patients showed hypertension (> 95th percentile), but more than half of them had no significant stenosis (defined as ≥30%). C was lower in CoA than in controls (3.30 ± 2.43 vs. 4.67 ± 2.21 [10-5 Pa-1 m-2]; p = 0.024). Significant differences in compliance were found between hyper- and normotensive patients (2.61 ± 1.60 vs. 4.11 ± 2.95; p = 0.01), and gothic and Romanesque arch geometry (2.64 ± 1.58 vs. 3.78 ± 2.81; p = 0.027). There was a good correlation between C and hypertension (r = 0.671; p < 0.01), but no correlation between C (and hypertension) and time or kind of repair, restenosis, or pressure gradients. CONCLUSION: The decreased compliance, a high rate of hypertension without restenosis, and independency of time and kind of repair confirm the hypothesis that CoA may not be limited to isthmus region but rather be a widespread (systemic) vascular anomaly at least in some of the CoA patients. Therefore, aortic compliance should be assessed in these patients to individually tailor treatment of CoA patients with restenosis and/or hypertension.

Cor triatriatum sinister with left anomalous pulmonary venous return to innominate vein.

Cor triatriatum sinister is a rare congenital abnormality, with varying signs and symptoms related to the anatomic features and the components of the accompanying cardiac abnormalities. We present a 3-year-old girl who underwent successful simultaneous operation with complete loss of the membrane and ligation of vertical vein by anomalous venous return. The principles for surgical management of cor triatriatum can be summarised as radical resection of the membrane and correction of other intracardiac anomalies.

Repair of an aorto-right ventricular tunnel in a newborn.

A newborn presented with an aorto-right ventricular tunnel, a defect connecting the left aortic sinus to the right ventricle. The patient underwent repair on 4th day of life.

Variable expression of Alagille syndrome in a family with a new JAG1 gene mutation.

We report the case of a patient with tetralogy of Fallot with absent pulmonary valve and familial Alagille syndrome who successfully underwent cardiac repair. The patient's sister had liver and congenital heart disease. The father had undergone liver transplantation but showed no significant cardiac abnormalities. A yet-unknown mutation of the JAG1 gene was discovered in this family with variable expression of Alagille syndrome.

Results of using cardiopulmonary bypass for spinal cord protection during surgical repair of complex aortic coarctation.

BACKGROUND: The aim of this study was to evaluate the surgical treatment of complex aortic coarctation using partial cardiopulmonary bypass to increase the spinal cord protection. METHODS: A total of 15 patients (age range from 7 to 48 years) underwent coarctation repair through a left posterolateral thoracotomy with cardiopulmonary bypass. Cannulation was performed via the descending aorta and the main pulmonary artery. In all, six surgeries were performed under hypothermic circulatory arrest and nine repairs were performed under mild hypothermia. The clinical outcome regarding the development of restenosis, as well as major neurologic complication, was studied. RESULTS: There was no mortality. None of the patients developed paraplegia. Of the 15 patients, two developed a recurrent stenosis at the proximal anastomosis between the aortic arch and the aortic prothesis at a mean follow-up of 5.5 years. In the remaining 13 patients, echocardiography and magnetic resonance imaging showed no evidence of a significant gradient. CONCLUSION: Complex aortic coarctation without hypoplasia of the proximal aortic arch and intra-cardiac anomalies can be repaired with low mortality and neurologic morbidity via a left thoracotomy using cardiopulmonary bypass. The use of cardiopulmonary bypass goes along with a low risk of spinal cord and lower body ischaemia and provides a sufficient amount of time for the anastomoses.

Extracorporeal life support with an integrated left ventricular vent in children with a low cardiac output.

BACKGROUND: The aim of this study was to evaluate our experience in central extracorporeal life support with an integrated left ventricular vent in children with cardiac failure. METHODS: Eight children acquired extracorporeal life support with a left ventricular vent, either after cardiac surgery (n = 4) or during an acute cardiac illness (n = 4). The ascending aorta and right atrium were cannulated. The left ventricular vent was inserted through the right superior pulmonary vein and connected to the venous line on the extracorporeal life support such that active left heart decompression was achieved. RESULTS: No patient died while on support, seven patients were successfully weaned from it and one patient was transitioned to a biventricular assist device. The median length of support was 6 days (range 5-10 days). One patient died while in the hospital, despite successful weaning from extracorporeal life support. No intra-cardiac thrombus or embolic stroke was observed. No patient developed relevant intracranial bleeding resulting in neurological dysfunction during and after extracorporeal life support. CONCLUSIONS: In case of a low cardiac output and an insufficient inter-atrial shunt, additional left ventricular decompression via a vent could help avoid left heart distension and might promote myocardial recovery. In pulmonary dysfunction, separate blood gas analyses from the venous cannula and the left ventricular vent help detect possible coronary hypoxia when the left ventricle begins to recover. We recommend the use of central extracorporeal life support with an integrated left ventricular vent in children with intractable cardiac failure.

Aortic uncrossing of the left circumflex aorta.

The following video tutorial presents the surgical correction of the left circumflex aortic arch in a 6-month-old boy with severe respiratory distress and stridor. The diagnosis was confirmed using cardiac catheterization and computed tomography. Intraoperative bronchoscopy showed marked compression of the trachea. An operation was planned to translocate the aortic arch anteriorly and to close the atrial septal defect. After a median sternotomy, the mediastinal structures were carefully mobilized and dissected. The trachea was carefully mobilized and the right ligamentum arteriosum was clipped and divided. Control of the aortic arch vessels, as well as the aberrant right subclavian artery from the right descending aorta, was achieved using vessel loops. An arterial line inserted in the femoral artery was connected to the heart-lung machine. Hence the surgical procedure was undertaken in selective antegrade cerebral perfusion combined with distal body perfusion, avoiding the need for deep hypothermic arrest. Careful mobilization of the complete course of the proximal and distal sections of the circumflex arch allowed its translocation from its retro-oesophageal course. The aortic stump distal to the left subclavian artery was closed by running polypropylene suture. An appropriate site on the ascending aorta was selected to ensure tension- and torsion-free anastomoses. Postoperative bronchoscopy confirmed relief of the tracheal compression.

Surgical Treatment of Atrial Septal Defects.

Atrial septal defects (ASDs) are among the most prevalent congenital cardiac malformations. Closure of the defect and repair of associated cardiac malformations are typically indicated if an ASD is hemodynamically significant or symptomatic. This narrative review aims to summarize key aspects of surgical ASD closures. A non-systematic literature review was conducted to cover surgically relevant aspects of (developmental) anatomy, morphology, and treatment. ASDs result from diverse developmental alterations, leading to subtype-specific associated cardiac malformations, meaning surgical therapy varies accordingly. Presently, surgical repair yields excellent outcomes for all ASD subtypes, with minimally invasive approaches, especially in adults, increasingly employed for ASD closure. Surgical ASD repair is safe with excellent results. However, familiarity with ASD subtypes and typically associated lesions is crucial for optimal patient management.

2 Rare Syndromes in 1 Patient: Determining the Cause of Sudden Cardiac Arrest.

A 19-year-old man survived sudden cardiac arrest caused by ventricular fibrillation during physical activity. The initial suspicion that this was caused by electrolyte imbalance proved to be wrong. Cardiac computed tomography revealed congenital heart disease. Coronary imaging is an essential component of the comprehensive diagnostic workup after sudden cardiac arrest.

Cyclooxygenase-2 expression in lung in patients with congenital heart malformations and pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a cause of morbidity in patients with congenital heart disease (CHD). It has been hypothesized that prostanoides participate in the development of PAH. The aim of this study was to show the potential expression of cyclooxygenase-2 (COX-2) in patients with CHD and PAH. PATIENTS AND METHODS: We included patients with isolated left-to-right shunts undergoing lung biopsy before or concomitantly with cardiac surgery between 2004 and 2009.For determination of COX-2 expression, histological and immunohistochemistry analyses as well as quantitative polymerase chain reaction (qPCR) were performed. RESULTS: We were able to show COX-2 protein overexpression in the lung tissue of children with CHD and PAH. Furthermore, we showed an increase in COX-1 gene expression and an even stronger induction of COX-2 by using qPCR and immunohistochemistry. CONCLUSIONS: We examined the expression of COX-2 in lung tissue from patients with CHD and PAH. We showed that COX-2 is expressed in diseased lung tissue, indicating a relationship between COX-2 and vascular remodeling in pulmonary arteries in CHD.

Temporary tricuspid valve detachment for ventricular septal defect closure: is it worth doing it?

BACKGROUND: Tricuspid valve detachment (TVD) may improve the access for closing certain ventricular septal defects (VSDs), but it has some potential risks. We aimed to study the benefits and drawbacks of this technique. METHODS: The midterm outcomes of all 20 patients who underwent a TVD closure for VSD were reviewed and compared with a control group of 15 patients with VSD closure without TVD. RESULTS: There was no significant residual shunt in either group at the last actuarial follow-up. Tricuspid regurgitation occurred in both groups (45% in the TVD group and 27% in the control group, P = .48). These lesions were considered insignificant in all patients. There were no atrioventricular blocks, and all patients were in sinus rhythm. The cardiopulmonary bypass times were significantly higher in the TVD group than in the control group (91.6 ± 17.2 minutes versus 68.3 ± 15.7 minutes, P ≤ .01), as were the aortic cross-clamping times (50.7 ± 12.1 minutes versus 35.9 ± 14.4 minutes, P ≤ .01). CONCLUSION: Our results, along with results from other series, suggest that TVD can be used effectively and safely for closure of certain VSDs.

Impact of hybrid procedure on pulmonary arterial dimensions and right ventricular load after biventricular repair.

BACKGROUND: Hybrid procedure with ductal stenting and bilateral pulmonary banding offers a temporary approach in high-risk neonates with complex congenital heart defects aiming biventricular repair. This procedure may also have negative impact concerning post-banding pulmonary stenosis resulting in right ventricular pressure load. METHODS: Between 2010 and 2021 we identified 5 patients with interrupted aortic arch and complex congenital heart defect who underwent hybrid procedure and staged biventricular repair ("hybrid-group"). Other 7 cases with interrupted aortic arch were corrected in the neonatal phase without hybrid procedure ("nonhybrid-group"). Detailed intra- and extracardiac features and surgical procedures were documented as well as pulmonary interventions during follow up. Pulmonary vessel size was assessed by diameter of left and right pulmonary artery in absolute and indexed values. RV pressure was evaluated invasively via catheterization. RESULTS: Survival in cases with hybrid procedure and staged biventricular repair was 91% for a follow-up time of 40.7 months (95% CI 26-55 months) and 100% in the non-hybrid-group. Postoperative results concerning left ventricular function showed normal LV dimensions and systolic function without relevant stenosis on distal aortic arch. Hybrid procedure was associated with impaired local pulmonary arterial diameter after debanding resulting in increased right ventricular pressure and need for interventions (number intervention per patient: hybrid group 1.7 ± 0.95, non-hybrid group 0.17 ± 0.41; P 0.003). CONCLUSIONS: Hybrid procedure in high-risk cases with interrupted aortic arch and staged biventricular repair shows good postoperative results with low perioperative mortality and normal left ventricular function. Due to potential risk of relevant pulmonary stenosis and right ventricular pressure load, follow up examinations must not only focus on left but also on the right heart.

Model-driven survival prediction after congenital heart surgery.

OBJECTIVES: The objective of the study was to improve postoperative risk assessment in congenital heart surgery by developing a machine-learning model based on readily available peri- and postoperative parameters. METHODS: Our bicentric retrospective data analysis from January 2014 to December 2019 of established risk parameters for dismal outcome was used to train and test a model to predict postoperative survival within the first 30 days. The Freiburg training data consisted of 780 procedures; the Heidelberg test data comprised 985 procedures. STAT mortality score, age, aortic cross-clamp time and postoperative lactate values over 24 h were considered. RESULTS: Our model showed an area under the curve (AUC) of 94.86%, specificity of 89.48% and sensitivity of 85.00%, resulting in 3 false negatives and 99 false positives.The STAT mortality score and the aortic cross-clamp time each showed a statistically highly significant impact on postoperative mortality. Interestingly, a child's age was barely statistically significant. Postoperative lactate values indicated an increased mortality risk if they were either constantly at a high level or low during the first 8 h postoperatively with an increase afterwards.When considering parameters available before, at the end of and 24 h after surgery, the predictive power of the complete model achieved the highest AUC. This, compared to the already high predictive power alone (AUC 88.9%) of the STAT mortality score, translates to an error reduction of 53.5%. CONCLUSIONS: Our model predicts postoperative survival after congenital heart surgery with great accuracy. Compared with preoperative risk assessments, our postoperative risk assessment reduces prediction error by half. Heightened awareness of high-risk patients should improve preventive measures and thus patient safety.

Surgical Treatment Following Stent Angioplasty for High-Risk Neonates With Critical Coarctation of the Aorta.

BACKGROUND: Neonatal coarctation of the aorta (CoA) is primarily treated by surgical repair. However, under certain high-risk constellations, initial stent angioplasty may be considered followed by surgical repair. We report our experience with this staged approach. Methods: All patients undergoing surgical CoA repair following prior stenting at our institution between January 2011 and December 2019 were included in this retrospective analysis. The patients were classified to be at high risk because of cardiogenic shock, associated complex cardiac malformations, neonatal infection, necrotizing enterocolitis, and extracardiac conditions, respectively. Outcomes were analyzed and compared with neonates who underwent surgical CoA repair without prior stenting in the same observation period. RESULTS: Twenty-six neonates received stent implantation at a median age of 20 days (IQR 9-33 days). Subsequent surgical repair was conducted at an age of 4.2 months (IQR 3.2-6.1 months) with a median body weight of 5.6 kg (IQR 4.5-6.5 kg). Cardiopulmonary bypass was applied in 96% of cases. Extended end-to-end anastomosis was possible in 11 patients. Extended reconstruction with patch material was necessary in the remaining patients. One fatality (3.8%) occurred 33 days postoperatively. At a median follow-up of 5.2 years after initial stenting, all remaining patients were alive; 15/25 patients (60%) were free from re-intervention. Of note, re-intervention rates were comparable in neonates (n = 76) who were operated on with native CoA (28/74 patients; 38%; P = .67). CONCLUSIONS: Neonatal stent angioplasty for CoA results in increased complexity of the subsequent surgical repair. Nevertheless, this staged approach allows to bridge high-risk neonates to later surgical repair with reduced perioperative risk and acceptable midterm outcomes.

Psychosocial Impact of Congenital Heart Diseases on Patients and Their Families: A Parent's Perspective.

BACKGROUND: Currently, over 90% of children with congenital heart disease (CHD) survive into adulthood. As a consequence the psychosocial impact on children and their families has become an important outcome measure. Therefore, the goal of this study was to assess the psychosocial impact from a parent's perspective and to identify possible predictors. METHODS: We included all parents of children who underwent open-heart surgery in the years 2010 and 2011 at the Department of Cardiothoracic Surgery at University Hospital Heidelberg and invited them to complete standardized questionnaires. Psychosocial outcome was measured via parent self- and proxy reporting of family burden (Family Burden Questionnaire, FaBel), health-related quality of life (KidScreen-10), developmental problems (Five-to-Fifteen, FTF), and mental health problems (Strength and Difficulties Questionnaire, SDQ). RESULTS: In total, 113 families returned the questionnaires completely (71.5%). The Aristotle Basic Complexity score and the STAT 2020 Score overall did not predict the psychosocial impact, whereas the number of surgical operations did significantly predict psychosocial impact across all domains in this study cohort. CONCLUSIONS: These data suggest that the number of surgical operations might be a relevant predictor for the long-term psychosocial impact on families suffering from CHD and a potential connecting factor for specialized psychological support. When setting up screening instruments or support programs the entire family must be considered.

Endothelial nitric oxide synthase gene polymorphism (Glu298Asp) and acute pulmonary hypertension post cardiopulmonary bypass in children with congenital cardiac diseases.

BACKGROUND: Intra-cardiac repair of congenital cardiac diseases in children with left-right shunt is often associated with acute elevation of pulmonary artery pressure following cardiopulmonary bypass. We studied the correlation between the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene and pulmonary hypertension in children with congenital cardiac diseases. METHODS AND RESULTS: A total of 80 children with congenital cardiac diseases at a median age of 3.8 years, ranged 0.1-36.2 years, and 136 controls were enrolled. Most patients presented with significant left-to-right shunt - pulmonary-to-systemic blood flow of 2.8, with a range from 0.6 to 7.5. In all, 40 out of 80 children showed pulmonary hypertension with mean pressure of 42, ranged 26-82, millimetres of mercury. Thirty-one out of 40 children underwent intra-cardiac repair and 15 out of 31 operated patients were found to have an acute elevation of pulmonary artery pressure after cardiopulmonary bypass. The Glu298Asp polymorphism was identified using polymerase chain reaction and restriction fragment length polymorphism. Both in patients and in controls, the genotype distribution corresponded to the Hardy-Weinberg equilibrium. The gene frequency for Glu298Glu, Glu298Asp and Asp298Asp was not different in the control group compared to the patients (Armitage trend test: p = 0.37). The endothelial nitric oxide synthase polymorphism was related to acute post-operative elevation of pulmonary artery pressure (genotypic frequency 53.3 versus 25%; Armitage trend test: p = 0.038). In addition, the allelic frequency of the Glu298Asp was related to post-operative pulmonary hypertension (Fischer's exact test: p = 0.048). The positive predictive value was 71.43%. CONCLUSION: Patients with left-to-right shunt are more likely to develop acute elevation of pulmonary artery pressure after cardiopulmonary bypass when presenting with the Glu298Asp polymorphism of the gene endothelial nitric oxide synthase. This could be used as a genetic marker for the predisposition for the development of pulmonary hypertension after intra-cardiac repair.