Has Propranolol Eradicated the Need for Surgery in the Management of Infantile Hemangioma?

BACKGROUND: To assess the impact of propranolol as the first-line treatment of infantile hemangioma (IH) on the need for surgery in the management of IH. METHODS: Retrospective study of 420 patients, with IH, referred to our multidisciplinary center between January 2005 and August 2014. Clinical data including sex, age at first consultation and at treatment initiation, location, size, number, aspect, and complication of IH, as well as the type of treatment were collected. Statistical analyses were conducted considering each patient and each tumor independently. RESULTS: A total of 625 IH(420 patients (P))were reviewed, 113 patients had more than one IH (26.91%). Median age at first consultation was 7 months old. Overall, 243 patients were treated (57.86%) using either surgery (n=128 P/141 IH), propranolol (n=79 P/89 IH), corticosteroids (n=51 P/56 IH), and/or laser (n=34 P /36 IH). Propranolol was effective in all but 2 infants with IH. Seven patients (n=7/79 P; 8.86%) initially treated with propranolol, still required surgery, in contrast to 18 patients (n=18/51 P; 35.29%) initially treated with corticosteroids, and 103 patients (n=103/290 P; 35.51%) with no medical treatment. Since the availability of propranolol, patients were less likely to undergo surgery (48 P versus 80 P; P-Value < 0.001). This demonstrated that the use of propranolol reduced the need for surgery (P-Value < 0.001 with an OR of 0.177: CI 95% 0.079-0.396). CONCLUSION: Propranolol has dramatically reduced the need for surgery, regarding indications and number of patients. Surgical correction remains important for sequelae management, non-responders or strawberry-like IH.

Use of One-minute Sit-to-stand Test to Predict Functional Exercise Capacity in Patients With Congenital Heart Disease.

INTRODUCTION: Field tests are commonly used as complements of cardiopulmonary exercise test (CPET) to evaluate the functional exercise capacity. The aims of this study were to validate the one-minute sit-to-stand test (STST) in congenital heart disease (CHD) children and to evaluate the possibility of predicting the peakVO2 using the STST in this paediatric population. METHODS: Children (8- to 18-year-old) followed for a CHD and performing CPET were recruited prospectively. Concomitantly, they performed STST. The heart rate (HR), oxygen saturation (SpO2), muscular fatigue and dyspnoea were recorded before (t0), immediately after (t1) and 1min after the end of the STST (t2). RESULTS: We observed a poor but significant correlation between the STST and the peakVO2 (r=0.306; p=0.013). A significant difference between girls and boys were observed for peakVO2 (p<0.001), HR t0 (p=0.030), HR t1 (p=0.002) and HR t2 (p<0.001). The proposed model of prediction, including the number of STST, weight, height and age explains 37% of the predicted peakVO2 variance. CONCLUSION: The STST can provide relevant data on physical capacity in children with CHD. When CPET cannot be performed, we therefore propose an alternative equation using the STST as a surrogate of peakVO2 in CHD children.

Atrial fibrillation in a pediatric patient caused by an unusual malignant etiology: A case report.

This case report describes a 15-year-old patient with a known congenital malformation syndrome and immune deficiency, presenting with new-onset atrial fibrillation (AF) after a recent diagnosis of an intrathoracic mass. Transthoracic echocardiography showed a structurally and functionally normal heart and workup confirmed a primary diffuse large B-cell lymphoma, with pericardial and left atrial involvement on cardiac magnetic resonance imaging. Electrical cardioversion was successfully performed to convert the AF and chemotherapy was promptly started. Antiarrhythmic treatment was continued for 6 weeks, without recurrent AF. We discuss the pathogenesis of AF in the setting of malignancies as well as the management strategies of AF, mainly based on adult guidelines.

Usefulness of serum neurofilament light in the assessment of neurologic outcome in the pediatric population: a systematic literature review.

Children undergoing general anesthesia and surgery in the early years of life are exposed to the possible neurotoxicity of anesthetic agents. Prospective studies have shown deficits in behavior, executive function, social communication, and motor function in children undergoing anesthesia and surgery. Different biomarkers of neuronal injury have been evaluated neuronal injury in the pediatric population, among which neurofilaments represent a significant advantage as they are proteins exclusively expressed in neuronal tissue. Our aim was to evaluate the utility of serum neurofilament light (NfL) as a prognostic biomarker of neuronal injury in the pediatric population. A literature search was performed on PubMed, Embase, and Cochrane Databases in November 2022 for studies concerning serum NfL in the pediatric population in addition to a neurological assessment. Inclusion criteria were as follows: (1) prospective or retrospective studies, (2) studies including pediatric population until the age of 18 years, (3) serum NfL sampling, and (4) evaluation of neurological outcome. Data collection regarding study design, pediatric age, serum NfL levels, and results for neurological assessment were extracted from each study. Four manuscripts met the inclusion criteria and evaluated the prognostic utility of serum NfL in neonatal encephalopathy in correlation with the neurodevelopmental outcome that was assessed by the Bayley Scales of Infant Development until the age of 2 years. Children with neonatal encephalopathy showed significantly higher serum NfL vs. healthy controls and high serum NfL levels predicted an adverse neurological outcome. The decrease of serum NfL to a nadir point between 10 and 15 years old reflects the brain growth in healthy controls. No studies were available in the perioperative period.  Conclusions: Serum NfL is a valuable biomarker in evaluating neuronal injury in the pediatric population. Further studies with perioperative serial sampling of serum NfL combined with standardized neurodevelopmental tests should be conducted to evaluate the neurotoxicity of anesthetic agents and monitor the effectiveness of specific neuroprotective strategies in pediatric patients undergoing anesthesia and surgery. What is Known: • Preclinical animal data have shown neurotoxicity of the anesthetic agents in the developing brain. • Data regarding anesthetic neurotoxicity in humans show limitations and no objective tools are available. What is New: • This systematic review showed that serum NfL is a valuable biomarker of neuronal injury in the pediatric population. • Perioperative use of serum NfL may be considered in future trials evaluating anesthetic neurotoxicity in the pediatric population and in monitoring neuroprotective strategies.

The burden and surveillance of RSV disease in young children in Belgium-expert opinion.

Infections with respiratory syncytial virus (RSV) can cause severe disease. In young children, RSV is the most common cause of lower respiratory tract illness and life-threatening infections most commonly occur in the first years of life. In adults, elderly and immunocompromised people are most vulnerable. Recently there has been an acceleration in the development of candidate RSV vaccines, monoclonal antibodies and therapeutics which are expected to become available in Europe within the next 2-10 years. Understanding the true burden of childhood RSV disease will become very important to support public health authorities and policy makers in the assessment of new therapeutic opportunities against RSV disease. A systematic literature search was performed to map local data on the burden of RSV disease and to evaluate available RSV surveillance systems. A group of 9 paediatric infectious diseases specialists participated in an expert panel. The purpose of this meeting was to evaluate and map the burden associated with RSV infection in children, including patient pathways and the epidemiological patterns of virus circulation in Belgium. Sources of information on the burden of RSV disease in Belgium are very limited. For the outpatient setting, it is estimated that 5-10% of young patients seen in primary care are referred to the hospital. Around 3500 children between 0 and 12 months of age are hospitalized for RSV-bronchiolitis every year and represent the majority of all hospitalizations. The current Belgian RSV surveillance system was evaluated and found to be insufficient. Knowledge gaps are highlighted and future perspectives and priorities offered. CONCLUSION: The Belgian population-based RSV surveillance should be improved, and a hospital-led reporting system should be put in place to enable the evaluation of the true burden of RSV disease in Belgium and to improve disease management in the future. WHAT IS KNOWN: • RSV bronchiolitis is a very important cause of infant hospitalization. • The burden of disease in the community is poorly studied and underestimated. WHAT IS NEW: • This expert opinion summarizes knowledge gaps and offers insights that allow improvement of local surveillance systems in order to establish a future-proof RSV surveillance system.

Last year of life of adults with congenital heart diseases: causes of death and patterns of care.

AIMS: Although life expectancy in adults with congenital heart diseases (CHD) has increased dramatically over the past five decades, still a substantial number of patients dies prematurely. To gain understanding in the trajectories of dying in adults with CHD, the last year of life warrants further investigation. Therefore, our study aimed to (i) define the causes of death and (ii) describe the patterns of healthcare utilization in the last year of life of adults with CHD. METHODS AND RESULTS: This retrospective mortality follow-back study used healthcare claims and clinical data from BELCODAC, which includes patients with CHD from Belgium. Healthcare utilization comprises cardiovascular procedures, CHD physician contacts, general practitioner visits, hospitalizations, emergency department (ED) visits, intensive care unit (ICU) admissions, and specialist palliative care, and was identified using nomenclature codes. Of the 390 included patients, almost half of the study population (45%) died from a cardiovascular cause. In the last year of life, 87% of patients were hospitalized, 78% of patients had an ED visit, and 19% of patients had an ICU admission. Specialist palliative care was provided to 17% of patients, and to only 4% when looking at the patients with cardiovascular causes of death. CONCLUSIONS: There is a high use of intensive and potentially avoidable care at the end of life. This may imply that end-of-life care provision can be improved. Future studies should further examine end-of-life care provision in the light of patient's needs and preferences, and how the healthcare system can adequately respond.

Treatment of a severe distal thoracic and abdominal coarctation with cutting balloon and stent implantation in an infant: From fetal diagnosis to adolescence.

Background and Aims: Abdominal coarctations are rare. Surgical treatment is difficult and requires re-interventions to adjust the graft material to patient growth. We report effective treatment by interventional catheterization in an infant with the concern to allow adjustment for growth and prevention of vessel damage. Methods and Results: After the diagnosis of abdominal coarctation at 27 weeks of gestation, an infant developed hypertension (170/70 mmHg) at 3 months of age despite medical therapy. Angio CT confirmed a 2 mm diameter, 2.3-cm-long coarctation of the descending aorta. At 4 months, a dilatation was performed using a 3 mm cutting balloon and a 5 mm Opta® balloon, Cordis®. Two noncovered Palmaz® Genesis™ XD PG1910P stents were required to keep the aortic lumen open. At 15 months, an Adventa™ V12 vascular 12 × 61 mm long covered stent was implanted to exclude an aneurysm which developed between the two stents. At 3 and 9.5 years, the stents were further dilated with a high-pressure balloon to reach 11 mm aortic diameter with no residual pressure gradient, and normal blood pressure. Conclusions: The use of cutting balloons and stent implantation is an effective way to relieve severe obstruction in middle aortic syndrome in neonates. The technical issues encountered were the need for a low profile sheath and material to avoid femoral artery damage, and the need to use stents that can be further expanded to adult size.

Torsade de pointe due to QT prolongation following erythromycin administration in a preterm infant.

BACKGROUND: Neonatal sepsis is a major cause of morbidity and mortality in preterm infants. Chorioamnionitis is an important risk factor for the development of sepsis, therefore neonates born to mothers developing signs of amnionitis need to be treated with antibiotics immediately after birth. Ureaplasma spp can be a causative agent of vaginal or intra amniotic infection needing antibiotic treatment. Macrolides are frequently used to treat maternal intrauterine infection, but antibiotic treatment of the neonate should be consciously chosen with consideration of potential side effects. Indeed, macrolides are great purveyors of heart rhythm disorders. CASE PRESENTATION: We describe the case of a 29 weeks preterm infant born to a mother with Ureaplasma spp infection. The baby was treated with erythromycin immediately after birth. During the second day of life, the baby presented some episodes of tachyarrhythmia with premature ventricular beats (PVBs) that were followed by a non-sustained ventricular tachycardia as high as 270 bpm leading to a cardiac arrest. After resuscitation, tachycardia resolved but the rhythm was characterised by numerous PVBs and an electrocardiogram (ECG) diagnosed a Long QT Syndrome (LQTS). Erythromycin was discontinued, and the rhythm normalised a few days after withdrawal. CONCLUSIONS: Erythromycin should be administered in neonates only if no other choice is available, as although generally well tolerated, its administration can be associated with QTc interval prolongation. When no other option is available, paediatricians should be aware to perform cardiac monitoring or at least serial ECGs before and during erythromycin administration.

Combined Algorithm-Based Adaptations of Insulin Dose and Carbohydrate Intake During Exercise in Children With Type 1 Diabetes: Results From the CAR2DIAB Study.

Objectives: To evaluate the evolution of subcutaneous glucose during two sessions of monitored aerobic exercise in children or adolescents with type 1 diabetes after adaptation of insulin doses and carbohydrate intake according to a combined algorithm. Methods: Twelve patients with type 1 diabetes (15.1 ± 2 years; diabetes duration: 9.5 ± 3.1 years) performed two series of exercise sessions after cardiac evaluation. The first series (TE#1) consisted in a monitored exercise of moderate to vigorous intensity coupled with a bout of maximum effort. The second series of exercises (TE#2) was carried out in real life during exercises categorized and monitored by connected watches. TE#2 sessions were performed after adaptation of insulin doses and fast-acting carbohydrates according to decision algorithms. Results: Patients did not experience episodes of severe hypoglycemia, symptomatic hyperglycemia, or hyperglycemia associated with ketosis. Analysis of CGM data (15 h) during TE#2 sessions revealed an overall improvement in glycemic average [± standard deviation] (104 ± 14 mg/dl vs. 122 ± 17 mg/dl during TE#1; p < 0.001), associated with a decrease in proportion of hyperglycemia in periods ranging from 4 h to 15 h after performing the exercises. The proportion of hypoglycemia was not changed, except during the TE#2 +4-8 h period, where a significant increase in hypoglycemia <60 mg/dl was observed (25% vs. 6.2%; p = 0.04), yet without concurrent complications. Conclusion: In our pediatric series, the application of algorithmic adaptations of insulin doses and carbohydrate intake has globally improved glycemic control during 15 h after real-time exercises performed by children and adolescents with type 1 diabetes.

Results of Coarctation Repair by Thoracotomy in Pediatric Patients: A Single Institution Experience.

BACKGROUND: Aortic coarctation is among the most common cardiovascular congenital abnormalities requiring repair after birth. Besides mortality, morbidity remains an important aspect. Accordingly, we reviewed our 20-year experience of aortic coarctation repair by thoracotomy, with emphasis on both short- and long-term outcomes. METHODS: From 1995 through 2014, 214 patients underwent coarctation repair via left thoracotomy. Associated arch lesions were distal arch hypoplasia (n = 117) or type A interrupted aortic arch (n = 6). Eighty-four patients had isolated coarctation (group 1), 66 associated ventricular septal defect (group 2), and 64 associated complex cardiac lesions (group 3). Median follow-up was 8.4 years. RESULTS: There was one (0.5%) procedure-related death. Nine (4.2%) patients died during index admission. In-hospital mortality was 0.7% in group 1 and 2 and 12.5% in group 3 (P < .001). No patient had paraplegia. Actuarial five-year survival was 97.5% in group 1, 94% group 2 and 66% in group 3. Recurrent coarctation developed in 29 patients, all but four (1.8%) successfully treated by balloon dilatation. Freedom from reintervention (dilatation or surgery) at five years was 86%. At hospital discharge, 28 (13.5%) patients were hypertensive. At follow-up, hypertension was present in 11 (5.3%) patients. CONCLUSIONS: Long-term results of aortic coarctation repair by thoracotomy are excellent, with percutaneous angioplasty being the procedure of choice for recurrences. Patient prognosis is dependent on associated cardiac malformations. In this study, the prevalence of late arterial hypertension was lower than previously reported.

Amiodarone-induced thyroid dysfunction in children: insights from the THYRAMIO study.

BACKGROUND: Amiodarone treatment is effective against various types of arrhythmias but is associated with adverse effects affecting, among other organs, thyroid function. Amiodarone-induced thyroid dysfunction was not thoroughly evaluated in children as it was in adults, yet this affection may lead to irreversible neurodevelopmental complications. Our study aimed to define the incidence and risk factors of amiodarone-induced thyroid dysfunction in children. METHODS: The study was designed as an observational study with a retrospective clinical series of 152 children treated by amiodarone in the Pediatric Cardiology Unit of our center from 1990 to 2019. All patients were divided into three groups according to their thyroid status: euthyroid, AIH (amiodarone-induced hypothyroidism) or AIT (amiodarone-induced thyrotoxicosis). Patients from these three groups were compared in terms of key clinical and therapeutic features. RESULTS: Amiodarone-induced thyroid dysfunction was present in 23% of patients. AIT (5.3%) was three times less common than AIH (17.7%), and its occurrence increased with older age (p < 0.05), treatment dosage (p < 0.05), treatment duration (p < 0.05) and the number of loading doses administered (p < 0.05). There were no distinctive clinical features between euthyroid and AIH groups. A multivariable prediction model of AIT was built, with a yield of 66.7% as positive predictive value and 96.7% as negative predictive value. CONCLUSION: We observed that one in five children developed amiodarone-induced thyroid dysfunction. Special attention is required for older children with a high dosage and long-term therapy and who received a large number of loading doses, since these children are at risk to develop AIT, which is more delicate to manage than AIH.

Influenza Vaccination in Patients With Congenital Heart Disease in the Pre-COVID-19 Era: Coverage Rate, Patient Characteristics, and Outcomes.

BACKGROUND: Influenza vaccination is the most commonly recommended immune prevention strategy. However, data on influenza vaccination in patients with congenital heart disease (CHD) are scarce. In this study, our goals were to: (1) measure vaccination coverage rates (VCRs) for influenza in a large cohort of children, adolescents, and adults with CHD; (2) identify patient characteristics as predictors for vaccination; and (3) investigate the effect of influenza vaccination on hospitalization. METHODS: A nationwide cohort study in Belgium included 16,778 patients, representing 134,782 vaccination years, from the Belgian Congenital Heart Disease Database Combining Administrative and Clinical Data (BELCODAC). Data over 9 vaccination years (2006-2015) were used, and patients were stratified into 5 age cohorts: 6 months to 4 years; 5-17 years; 18-49 years; 50-64 years; and 65 years and older. RESULTS: In the respective age cohorts, the VCR was estimated to be 6.6%, 8.0%, 23.9%, 46.6%, and 72.8%. There was a steep increase in VCRs as of the age of 40 years. Multivariable logistic regression showed that higher anatomical complexity of CHD, older age, presence of genetic syndromes, and previous cardiac interventions were associated with significantly higher VCRs. Among adults, men had lower and pregnant women had higher VCRs. The association between influenza vaccination and all-cause hospitalization was not significant in this study. CONCLUSIONS: The influenza VCR in people with CHD is low, especially in children and adolescents. Older patients, particularly those with complex CHD, are well covered. Our findings should inform vaccination promotion strategies in populations with CHD.

Different levels of care for follow-up of adults with congenital heart disease: a cost analysis scrutinizing the impact on medical costs, hospitalizations, and emergency department visits.

AIM: To scrutinize the economic impact of different care levels, such as shared care, in the follow-up of adult congenital heart disease (ACHD) patients. METHODS: The BELgian COngenital heart disease Database combining Administrative and Clinical data (BELCODAC) was analyzed. Patients (N = 6579) were categorized into five care levels based on their cardiac follow-up pattern between 2006 and 2010. Medical costs, hospitalizations, and emergency department visits were measured between 2011 and 2015. RESULTS: In patients with moderate lesions, highly specialized cardiac care (HSC; exclusive follow-up by ACHD specialists) and shared care with predominantly specialized cardiac care (SC+) were associated with significantly lower medical costs and resource use compared to shared care with predominantly general cardiac care (SC-) and general cardiac care (GCC). In the patient population with mild lesions, HSC was associated with better economic outcomes than SC- and GCC, but SC+ was not. HSC was associated with fewer hospitalizations (- 33%) and less pharmaceutical costs (- 46.3%) compared to SC+. Patients with mild and moderate lesions in the no cardiac care (NCC) group had better economic outcomes than those in the GCC and SC- groups, but post-hoc analysis revealed that they had a different patient profile than patients under cardiac care. CONCLUSION: More specialized care levels are associated with better economic outcomes in patients with mild or moderate lesions in cardiac follow-up. Shared care with strong involvement of ACHD specialists might be a management option to consider. Characteristics of patients without cardiac follow-up but good medium-term economic prospects should be further scrutinized.

Creating the BELgian COngenital heart disease database combining administrative and clinical data (BELCODAC): Rationale, design and methodology.

BACKGROUND: Congenital heart disease (CHD) entails a broad spectrum of malformations with various degrees of severity and prognosis. Consequently, new and specific healthcare needs are emerging, requiring responsive healthcare provision. Research on this matter is predominantly performed on population-based databases, to inform clinicians, researchers and policy-makers on health outcomes and economic burden of CHD. Most databases contain data either from administrative sources or from clinical systems. We describe the methodological design of the BELgian COngenital Heart Disease Database combining Administrative and Clinical data (BELCODAC), to investigate patients with CHD. METHODS: Data on clinical characteristics from three university hospitals in Belgium (Leuven, Ghent and Brussels) were merged with mortality and socio-economic data from the official Belgian statistical office (StatBel), and with healthcare use data from the InterMutualistic Agency, an overarching national organization that collects data from the seven sickness funds for all Belgian citizens. Over 60 variables with multiple entries over time are included in the database. RESULTS: BELCODAC contains data on 18,510 patients, of which 8926 patients (48%) have a mild, 7490 (41%) a moderately complex and 2094 (11%) a complex anatomical heart defect. The most prevalent diagnosis is Ventricular Septal Defect in 3879 patients (21%), followed by Atrial Septal Defect in 2565 patients (14%). CONCLUSIONS: BELCODAC comprises longitudinal data on patients with CHD in Belgium. This will help build evidence-based provision of care to the changing CHD population.

Quality of life assessment in children before and after a successful ablation for supraventricular tachycardia.

BACKGROUND AND OBJECTIVES: Young patients suffering from rhythm disorders have a negative impact in their quality of life. In recent years, ablation has become the first-line therapy for supraventricular arrhythmias in children. In the light of the current expertise and advancement in the field, we decided to evaluate the quality of life in young patients with supraventricular arrhythmias before and after a percutaneous ablation procedure. METHODS: The prospective cohort consisted of patients <18 years with structurally normal hearts and non-pre-excited supraventricular arrhythmias, who had an ablation in our centre from 2013 to 2018. The cohort was evaluated with the PedsQL™ 4.0 Generic Core Scales self-questionnaire prior to and post-ablation. RESULTS: The final cohort included 88 patients consisted of 52 males (59%), with a mean age at ablation of 12.5 ± 3.3 years. Forty-two patients (48%) had a retrograde-only accessory pathway mediating the tachycardia, 38 (43%) had atrio-ventricular nodal re-entrant tachycardia, 7 (8%) had ectopic atrial tachycardia, and 1 (1%) had atrial flutter. The main reason for an ablation was the patient's choice in 53%. There were no severe complications. Comparison between the baseline and post-ablation assessments showed that patients reported significant improvement in the scores for physical health, emotional and social functioning, as well as in the total scores. CONCLUSIONS: The present study demonstrates that the successful treatment of supraventricular arrhythmias by means of an ablation results in a significant improvement in the quality of self-reported life scores in young patients.

Impaired pulmonary function and its association with clinical outcomes, exercise capacity and quality of life in children with congenital heart disease.

BACKGROUND: Impaired pulmonary function is an independent predictor of mortality in adult congenital heart disease (CHD), but has been scarcely studied in the paediatric CHD population. AIMS: To compare the pulmonary function of children with CHD to healthy controls, and evaluate its association with clinical outcomes, exercise capacity, and quality of life. METHODS: Cross-sectional multicentre study among 834 children (555 CHD and 279 control subjects) who underwent a complete spirometry and a cardiopulmonary exercise test (CPET). The 5th centile (Z-score = -1.64) was used to define the lower limit of normal. The association of clinical and CPET variables with spirometry was studied using a multivariate analysis. Children and their parents filled in the Kidscreen health-related quality of life questionnaire. RESULTS: Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) Z-scores values were lower in children with CHD than controls (-0.4 ±â€¯1.5 vs. 0.4 ±â€¯1.3, P < 0.001 and -0.5 ±â€¯1.4 vs. 0.4 ±â€¯1.2, P < 0.001, respectively), without any obstructive airway disorder. Restrictive pattern was more frequent in CHD patients than in controls (20% vs. 4%, P < 0.0001). FVC Z-scores were predominantly impaired in complex CHD, such as heterotaxy (-1.1 ±â€¯0.6), single ventricle (-1.0 ±â€¯0.2), and complex anomalies of the ventricular outflow tracts (-0.9 ±â€¯0.1). In multivariate analysis, FVC was associated with age, body mass index, peak oxygen uptake, genetic anomalies, the number of cardiac surgery and cardiac catheter procedures. FVC and FEV1 correlated with self and proxy-related quality of life scores. CONCLUSION: These results suggest that pulmonary function should be monitored early in life, from childhood, in the CHD population. TRIAL REGISTRATION NUMBER: NCT01202916, post-results.

Correlation Between Cardiopulmonary Exercise Test, Spirometry, and Congenital Heart Disease Severity in Pediatric Population.

Congenital heart disease (CHD) is a common chronic disease. This study aimed to verify the relationship between spirometry and exercise capacity in children, considering the CHD severity. All cardiopulmonary exercise testing (CPET) and Spirometry from CHD children (5-18 years) were retrospectively reviewed during three years. CPET and Spirometry were analyzed and correlated based on the CHD severity[modified Ross classification (mR)]. Patients (n = 321) were analyzed and subdivided for CHD severity (n = 49, n = 149, n = 80, n = 43, from mR1 to mR4, respectively). The maximal workload (Wmax) in mR1 and mR2 was higher than in patients from mR3 and mR4. Peak oxygen uptake (peak VO2) was reduced in mR3 and mR4 compared to mR1 and mR2. Carbon dioxide output was only significantly lower in mR4. Although spirometric parameters were globally in the normal range, forced expiratory volume and forced vital capacity were different between subgroups (p < 0.001 and p = 0.002, respectively). Wmax and peakVO2 were weakly or moderately but significantly correlated with spirometry. Respiratory exchange ratio and final blood oxygen saturation were only significantly and weakly correlated to obstruction in small airways. The most severe CHD patients had lower exercise capacity and lung function parameters. A weak to moderate correlation between CPET and spirometry was found. However, the lung function reported in our study was normal, but with a negative correlation with the age. It reinforces the benefits of precocious and regularly spirometry and CPET assessment in CHD children.

Distal Aortic Arch Hypoplasia and Coarctation Repair: A Tailored Enlargement Technique.

BACKGROUND: Several techniques have been described to correct coarctation associated with distal arch hypoplasia. However, in neonates, residual gradients are frequently encountered and influence long-term outcome. We reviewed our experience with an alternative technique of repair combining carotid-subclavian angioplasty and extended end-to-end anastomosis. METHODS: From 1998 through 2014, 109 neonates (median age, 9 days) with coarctation and distal arch hypoplasia (n = 106) or type A interrupted aortic arch (n = 3) underwent repair using this technique. Thirty patients had isolated lesions (group 1), 44 associated ventricular septal defect (group 2), and 35 associated complex cardiac lesions (group 3). Median follow-up was 98 months. RESULTS: Repair was performed via left thoracotomy in 97%. There was one procedural-related death (0.9%) and overall five patients died during index admission (4.6%). Ten deaths were recorded at follow-up. Actuarial five-year survival was 86% (100% in group 1, 91% group 2, and 66% in group 3). Recurrent coarctation (clinical or invasive gradient >20 mm Hg) developed in 15 patients, all but 2 successfully treated by balloon dilatation. Freedom from any reintervention (dilatation or surgery) at five years was 86%. Only two patients were on antihypertensive drugs at last follow-up. CONCLUSIONS: This combined technique to correct distal arch hypoplasia and isthmic coarctation results in low mortality and acceptable recurrence rate. It preserves the left subclavian artery and allows enlargement of the distal arch diameter. Late outcome is excellent with very low prevalence of late arterial hypertension.

Recent Experience and Follow-Up After Surgical Closure of Secundum Atrial Septal Defect in 120 Children.

While percutaneous catheter closure proves an effective treatment for secundum atrial septal defect (ASD2), some child patients require surgical closure. We assessed the risks associated with isolated surgical ASD2 closure by reviewing the outcomes of 120 children operated on between 1999 and 2011 (mean age 4.6 ± 3.9 years, mean weight 17 ± 12 kg). Direct sutures were performed in 4% and patch closures in 96%. The mean cardiopulmonary bypass duration was 38 ± 14 min, aortic cross-clamp time 19 ± 9 min, intensive care unit length of stay 1.6 ± 1.1 days, hospital stay 11.2 ± 5.1 days. There were no complications in 60 patients (50%) and major complications in 8 (6.7%), with 1 patient (0.8%) dying of pneumonia-induced sepsis, 2 (1.7%) requiring revision surgery, 3 (2.5%) requiring invasive treatment (2 pericardial drainage, 1 successful resuscitation), and 2 (1.7%) presenting thromboembolisms (1 cerebral stroke, 1 cardiac thrombus). In hospital minor complications occurred in 22 patients: 17 pericardial effusions (15%), 15 infections requiring treatment (12.5%), 1 sternal instability (0.8%), 4 anemias requiring transfusion (3.3%), 7 pulmonary atelectasis (6%), and 2 post-extubation glottis edema (1.7%). At early outpatient follow-up, complications occurred in 21 patients: 16 (13.3%) pericardial effusions, 4 (3.3%) infections requiring treatment, and 3 (2.5%) keloid scarring. No complications occurred during long-term follow-up. In line with published data, mortality was low (0.8%), yet major complications (6.7%) were more common in these cases than those following percutaneous ASD2 closure. Minor complications were frequent (43%) with no long-term sequelae.

Dnmt3a-mediated inhibition of Wnt in cardiac progenitor cells improves differentiation and remote remodeling after infarction.

Adult cardiac progenitor cells (CPCs) display a low capacity to differentiate into cardiomyocytes in injured hearts, strongly limiting the regenerative capacity of the mammalian myocardium. To identify new mechanisms regulating CPC differentiation, we used primary and clonally expanded Sca-1+ CPCs from murine adult hearts in homotypic culture or coculture with cardiomyocytes. Expression kinetics analysis during homotypic culture differentiation showed downregulation of Wnt target genes concomitant with increased expression of the Wnt antagonist, Wnt inhibitory factor 1 (Wif1), which is necessary to stimulate CPC differentiation. We show that the expression of the Wif1 gene is repressed by DNA methylation and regulated by the de novo DNA methyltransferase Dnmt3a. In addition, miR-29a is upregulated early during CPC differentiation and downregulates Dnmt3a expression, thereby decreasing Wif1 gene methylation and increasing the efficiency of differentiation of Sca-1+ CPCs in vitro. Extending these findings in vivo, transient silencing of Dnmt3a in CPCs subsequently injected in the border zone of infarcted mouse hearts improved CPC differentiation in situ and remote cardiac remodeling. In conclusion, miR-29a and Dnmt3a epigenetically regulate CPC differentiation through Wnt inhibition. Remote effects on cardiac remodeling support paracrine signaling beyond the local injection site, with potential therapeutic interest for cardiac repair.