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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. ispartof: INTERNATIONAL JOURNAL OF CARDIOLOGY vol:316 pages:72-78 ispartof: location:Netherlands status: published

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 ™ 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.

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. ispartof: CANADIAN JOURNAL OF CARDIOLOGY vol:37 issue:9 pages:1472-1479 ispartof: location:England status: published

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. ispartof: EUROPEAN JOURNAL OF HEALTH ECONOMICS vol:22 issue:6 pages:951-960 ispartof: location:Germany status: published

ObjectivesTo 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.MethodsTwelve 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.ResultsPatients 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 vs. 6.2%; p = 0.04), yet without concurrent complications.ConclusionIn 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.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by Research Foundation Flanders [grant numbers G097516N to PM, 12E9816N to EG and 1154719N to LVB]; the King Baudouin Foundation (Fund Joseph Oscar Waldmann-Berteau & Fund Walckiers Van Dessel); the National Foundation on Research in Pediatric Cardiology; and the Swedish Research Council for Health, Working Life and Welfare -FORTE (grant number STYA-2018/0004). OnBehalf BELCODAC consortium Background Although recent position papers have discussed and advocated for the integration of palliative care in the treatment course of adults with congenital heart defects (CHD), empirical studies reporting to what extent palliative care is currently provided, are still lacking. Purpose (1) To explore the current provision of palliative care to adults with CHD in the last 6 months of their life; and (2) to describe the profile of patients who received palliative care. Methods In this retrospective study, data of deceased adult patients included in the BELgian COngenital heart disease Database combining Administrative and Clinical data (BELCODAC) were analysed. Palliative care provision (i.e., admission to palliative care ward, or palliative care at home) was identified using nomenclature codes. The level of anatomical complexity was based on the Bethesda classification. Descriptive analyses were performed. Results During the period 2006-2016, 480 adults with CHD died (mean age: 54.4y; 45% simple CHD, 43% moderate CHD, 12% complex CHD). We identified that 75 patients (16%) had at least one nomenclature code linked to palliative care in the last 6 months of their life. More specifically, 16 patients were admitted to an inpatient palliative care service and 67 patients received palliative care at home. Of the patients who received palliative care at home, 40 patients were cared for by a multidisciplinary team specialized in palliative care provision and 59 patients received care from nurses and/or general practitioners while being recognized as a palliative patient. A total of 8 patients received palliative care both at the inpatient palliative care service and at home. Of the 75 patients receiving palliative care, 44 (59%) had a neoplasm as the primary cause of death and a cardiac cause of death was reported for 10 patients (13%) (see Figure 1). The mean age of patients receiving palliative care was 57.9 years. Most patients receiving palliative care had a simple CHD (n = 40; 53%), 29 patients (39%) had a moderate lesion, and 6 patients (8%) had a complex lesion. That means that, respectively, 19%, 14%, and 11% of all deceased patients with a simple, moderate, and complex heart lesion received palliative care. Conclusions This is the first exploratory study on palliative care in adults with CHD. About one in six patients who died received palliative care. Of those who received palliative care, the cause of death was in most cases of a non-cardiac nature. Further research is needed to investigate the care trajectories and care needs of adults with CHD in the last months of life. Figure 1. Causes of death of adults with CHD who received palliative care in the last 6 months of life (n = 75).

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 ± 1.5 vs. 0.4 ± 1.3, P < 0.001 and -0.5 ± 1.4 vs. 0.4 ± 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 ± 0.6), single ventricle (-1.0 ± 0.2), and complex anomalies of the ventricular outflow tracts (-0.9 ± 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.

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

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.

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.

Objective: Cost-of-illness studies in Adult Congenital Heart Disease (ACHD) have mainly been limited to hospitalizations. This is the first paper to provide a comprehensive overview from a societal perspective including inpatient and outpatient medical costs, and absenteeism- and unemployment-related societal costs. Methods: A retrospective longitudinal (2006-2015) database analysis was performed in Belgium combining administrative and clinical databases (n = 10,572). Trends in resource use and costs per patient year were standardized to assess the impact of changes in the patient population composition. Generalized Linear Mixed Models assessed the impact of age, sex, lesion complexity, and time. Costs were converted to 2018 values. Results: Medical costs per patient year increased from (sic)3490 to (sic)4536 with a milder increase in patients with severe lesions. Although unemployment-related costs decreased, total societal costs increased due to more long-term (>= 1 yr) invalidity. An increase in long-term invalidity was particularly found in patients >= 30 yrs and in patients with mild or moderate lesions. Resource use (e.g., dental care, nursing care, physiotherapy, emergency department) increased substantially in all patient groups over time. The annual percentage of patients with severe lesions receiving any cardiac and specialized cardiac follow-up increased with respectively 11 and 13 percent points to 81% and 52%, with a simultaneous decrease in hospitalization rate. Conclusion: Medical cost increases in ACHD are most pronounced in patients with mild and moderate lesions, relatable to their higher age. Economic data are necessary to allocate resources efficiently to ensure sustainable, qualitative care in an ageing patient population with strong increases in medical and long-term invalidity-related costs.

Over the past 20 years, closure of a secundum Atrial Septal Defect (ASD) has switched from a surgical approach to a transcatheter percutaneous approach...

Objectives To analyse our institutional results in the setting of paediatric aortic valve (AV) repair. Primary end-points were overall survival, freedom from AV reoperation and freedom from AV replacement. Methods A retrospective analysis of all patients under 18 years of age operated on from 1977 to 2015 in a single tertiary care level institution. Patients were included if they benefited from any type of AV repair procedure, including commissurotomy, leaflet shaving or plication, or leaflet augmentation. All data were gathered from patients' medical records, operative reports and referring paediatric cardiologists. The median follow-up was 50 months (IQR [13-140]). Results Sixty-six patients were included. Indications for surgery were aortic stenosis, aortic regurgitation and mixed disease in 13 (19%), 36 (55%) and 17 (26%) patients, respectively. According to El Khoury's functional classification, among the 55 patients with some degree of regurgitation there were 5 type Ib regurgitation, 23 type II and 27 type III. During AV repair, additional procedures were performed in 36 patients, VSD closure, subaortic membrane resection and mitral valve repair being the most frequent (18, 8 and 7 patients). RACHS score was predominantly 2 (98.5% of patients). The in-hospital mortality rate was 1.5% (1/66). Major morbidity included 10 pericardial effusions (1 pericardocentesis), 1 low cardiac output syndrome and 1 stroke. There were three late deaths (at 104, 140 and 179 months after repair). All were cardiac related. Overall 5- and 10-year survival rates were 100 and 95.7%. The rates of freedom from AV reoperation and AV replacement at 5 and 10 years were 90.6, 72.1 and 92.5, 82.7%, respectively. During follow-up, there was no occurrence of valve-related complication (endocarditis, thromboembolism and bleeding). Conclusions In our experience, AV repair in the paediatric population provides excellent results in terms of both overall survival and valve-related reoperation. It obviates the need for chronic anticoagulation and in most cases delays the time at which more complex surgery such as the Ross procedure should be undertaken.

Objectives Previous research in adult congenital heart disease (ACHD) patients suggested better clinical and managerial outcomes following specialized over general cardiac follow-up. The impact of different care levels, such as shared care, remained uninvestigated. Methods Propensity score analyses were performed on the BELgian COngenital heart disease Database combining Administrative and Clinical data (BELCODAC). Adult patients who ever attended a specialized congenital cardiology clinic (N=6,579) were categorized in five care levels based on their cardiac follow-up pattern between 2006 and 2010. Medium-term (2011-2015) economic outcomes were medical costs and resource use (i.e., hospitalizations and emergency department visits). Results Respectively 51.5% and 80% of patients with moderate and mild lesions were categorized in the general cardiac care (GCC) or no cardiac care group (NCC). 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 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 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. Conclusions 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

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 one second (FEV1) Z-scores values were lower in children with CHD than controls (− 0.4 ± 1.5 vs. 0.4 ± 1.3, P Conclusion These results suggest that pulmonary function should be monitored early in life, from childhood, in the CHD population.

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.

The cardiopathogenic role of autoantibodies (aabs) directed against β1-adrenoreceptors (β1-AR) is well established. In mouse models, they cause progressive dilated cardiomyopathy (DCM) whose characterization with echocardiography requires prolonged protocols with numerous animals, complicating the evaluation of new treatments. Here, we report on the characterization of β1-aabs-induced DCM in mice using 11.7T MRI. C57BL/6J mice (n = 10 per group) were immunized against the β1-AR and left ventricular (LV) systolic function was assessed at 10, 18 and 27 weeks. Increase in LV mass/tibial length ratio was detected as the first modification at 10 weeks together with dilation of cavities, thereby outperforming echocardiography. Significant impairment in diastolic index was also observed in immunized animals before the onset of systolic dysfunction. Morphometric and histological measurements confirmed these observations. The same protocol performed on β3-AR-overexpressing mice and wild-type littermates (n = 8–12 per group) showed that transgenic animals were protected with reduced LV/TL ratio compared to wild-type animals and maintenance of the diastolic index. This study demonstrates that MRI allows a precocious detection of the subtle myocardial dysfunction induced by β1-aabs and that β3-AR stimulation blunts the development of β1-aabs-induced DCM, thereby paving the way for the use of β3AR-stimulating drugs to treat this autoimmune cardiomyopathy.

The online version of the original article can be found under doi: 10.1007/s00395-016-0565-2 .

Backgroundpeak oxygen uptake (VO2) correlates with health related quality of life (QoL) in adults with heart failure. Cardio-pulmonary exercise test (CPET) is recommended in the follow-up of adults with congenital heart diseases (CHD). Few data is available as regards correlation between CPET and QoL among children with CHD.Methods and results202 CHD children aged 8 to 18 performed a CPET (treadmill n=96, cycle-ergometer n=106). CHD severity was stratified into 4 groups. All children and parents filled out the Kidscreen QoL questionnaire. Peak VO2, anaerobic threshold (AT), oxygen pulse followed a downward significant trend with increasing CHD severity and conversely for VE/VCO2 slope. Self-reported and parent-reported physical well-being QoL scores correlated with peak VO2 (respectively r=0.27, p

Cardiac MRI can predict the likely tumor type in the majority of children with a cardiac mass. A comprehensive imaging protocol is essential for accurate diagnosis. However, histologic diagnosis remains the gold standard, and in some cases malignancy cannot be definitively excluded on the basis of cardiac MRI images alone.

OBJECTIVE: To analyze the implication of the beta3-adrenoceptor (beta3-AR) pathway in human septic myocardium and a murine model of sepsis, a condition associated with myocardial depression. METHODS AND RESULTS: beta3-AR and eNOS protein abundance were increased (332+/-66.4% and 218+/-39.3; P

International audience; To assess the health-related quality of life (QoL) in children with congenital heart diseases (CHD) with a validated questionnaire in comparison with control children. We prospectively recruited 282 children with CHD aged from 8 to 18 years in two tertiary care centers (France and Belgium) and 180 same-age controls in randomly selected French schools. Children's QoL was self-reported with the KIDSCREEN-52 questionnaire and reported by parents with the KIDSCREEN-27. QoL scores of each dimension were compared between CHD and controls and between the classes of disease severity. Both centers were comparable for most demographic and clinical data. Age- and gender-adjusted self-reported QoL scores were lower in CHD children than in controls for physical well-being (mean ± SEM 45.97 ± 0.57 vs 50.16 ± 0.71, p

In the presence of new surgical techniques, the treatment of congenital valvular aortic stenosis is under debate. We reviewed the results and late outcomes of all 93 patients aged 1 day to 18 years, treated with balloon valvuloplasty (BAV) as first-line therapy for congenital aortic valve stenosis in our center from January 1991 to May 2012. Mean age at procedure time was 2.4 years; 37 patients underwent BAV at age ≤30 days (neonates), 29 patients at age ≥1 month and

3-Hydroxy-3-methylglutaryl (HMG)–coenzyme A reductase inhibitors or statins exert direct beneficial effects on the endothelium in part through an increase in nitric oxide (NO) production. Here, we examined whether posttranslational modifications of the endothelial NO synthase (eNOS) could account for the proangiogenic effects of statins. We used endothelial cells (ECs) isolated from cardiac microvasculature, aorta, and umbilical veins, as well as dissected microvessels and aortic rings, that were cultured on reconstituted basement membrane matrix (Matrigel). Tube or precapillary formation was evaluated after statin treatment, in parallel with immunoblotting and immunoprecipitation experiments. Atorvastatin stimulated NO-dependent angiogenesis from both isolated and outgrowing (vessel-derived) ECs, independently of changes in eNOS expression. We found that in macro- but not microvascular ECs, atorvastatin stabilized tube formation through a decrease in caveolin abundance and its inhibitory interaction with eNOS. We also identified the chaperone protein hsp90 as a key target for the proangiogenic effects of statins. Using geldanamycin, an inhibitor of hsp90 function, and overexpression of recombinant hsp90, we documented that the statin-induced phosphorylation of eNOS on Ser1177 was directly dependent on the ability of hsp90 to recruit Akt in the eNOS complex. Finally, we showed that statin promoted the tyrosine phosphorylation of hsp90 and the direct interaction of hsp90 with Akt, which further potentiated the NO-dependent angiogenic processes. Our study provides new mechanistic insights into the NO-mediated angiogenic effects of statins and underscores the potential of these drugs and other modulators of hsp90 and caveolin abundance to promote neovascularization in disease states associated or not with atherosclerosis.

One drawback of the arterial switch operation for treating transposition of the great arteries is the occurrence of coronary lesions, found during follow-up in about 5% of (a)symptomatic children. The established corrective procedures include coronary artery proximal patch arterioplasty or coronary artery bypass grafting (CABG). To avoid aortic manipulations and extracorporeal circulation, off-pump coronary artery bypass (OPCAB) has become increasingly used in the adult population. We report a case of OPCAB revascularization in a symptomatic 2-year-old child.

Crouzon syndrome is a rare genetic disorder characterised mainly by distinctive malformations of the skull and facial region and caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. No study reported on oedemas related to lymphatic system abnormalities in these patients. A case of Crouzon syndrome displaying classic facial anomalies but also with bilateral lower limb oedema is reported in whom lymphoscintigraphic investigation of the limbs clearly delineated the presence of lymphatic system anomalies.

Background Cardiotoxic chemotherapy including anthracyclines remains a standard of care in paediatric cancers. Recent data suggest that heart failure secondary to chemotherapy is, to some degree, reversible, but requires early detection and prompt intervention. Since a substantial proportion of paediatric patients still develop heart failure, this work aims to develop a follow-up protocol based on cMRI to evaluate the patient’s cardiovascular function and haemodynamics, as well as myocardial iron overload, perfusion and viability.

Although normothermia and warm blood cardioplegia are widely used in adults, cold crystalloids and hypothermia remain routinely used in pediatric cardiac surgery. The superiority of either technique in both brain and myocardial protection remains controversial. We designed a prospective randomized study to compare both approaches in terms of early myocardial protection and late neurodevelopmental status.From 2004 to 2005, 47 patients were randomly assigned to either mild hypothermia associated to cold crystalloid cardioplegia (CCC, 22 patients) or normothermia with intermittent warm blood cardioplegia (IWBC, 25 patients). Intramyocyte adenosine triphosphate (ATP) was measured before, during and after cardioplegic arrest and results between groups were compared. In addition to their cardiac status, early and late neurologic assessment was performed by psychometric evaluation tests.Intracellular ATP levels were not significantly different between the two groups. However, intragroup comparison revealed different profiles according to myocardial protection: in the normothermia/warm blood cardioplegia group, ATP concentration increased during cardioplegic arrest and returned to initial values afterward (11 nmol mg(-1) vs 21 nmol mg(-1) vs 10 nmol mg(-1), p0.001), such changes did not occur in the cold protocol (17 nmol mg(-1) vs 19 nmol mg(-1) vs 14 nmol mg(-1), p = NS). Early neurological outcome was similar in both groups. At late follow-up (mean = 4 years), no significant difference was observed between the two groups.This study demonstrates that normothermia/IWBC protocols are not deleterious when compared with more conventional approaches. A more physiologic ATP steady state, reflecting the absence of cellular ischemic insult was observed in the IWBC group. Importantly, no significant difference was found between IWBC and CCC groups in terms of early and late neurodevelopmental status.

An 11-year-old boy presented with mild shortness of breath and tachycardia and was diagnosed with a huge left ventricular aneurysm ruptured in a secondary pseudoaneurysm. This report highlights the complementary use of echocardiography and cardiac magnetic resonance imaging in the preoperative assessment of this anomaly.

Ectopia cordis is a rare congenital defect commonly associated with intra- and extra-cardiac anomalies. This report highlights the complimentary use of echocardiography and cardiac magnetic resonance imaging for detailed prenatal characterization of the anomaly at 23-week gestation.

Among the clinically relevant congenital coronary malformations, origin from the wrong aortic sinus seems to be the most common in young trained athletes who die suddenly. The reported incidence is 0.92% for anomalous origin of the right coronary artery (RCA) from the left sinus and 0.15% for the left coronary artery (LCA) from the right sinus. ' However, these data likely underestimate the true incidence of these abnormalities because these angiographic studies were presumably performed for other clinical indications. In a recent study of 6.3 million US Army recruits, Eckart and colleagues 2 reviewed the medical records of 277 nontraumatic deaths and found that 34% were the result of coronary anomalies. No coronary anomaly other than anomalous origin of the LCA from the right sinus of Valsalva was associated with cardiac death.

Background— Coronary vessel tone is modulated in part by β-adrenergic relaxation. However, the implication of specific β-adrenoceptor subtypes and their downstream vasorelaxing mechanism(s) in human coronary resistance arteries is poorly defined. β 3 -Adrenoceptors were recently shown to vasodilate animal vessels and are expressed in human hearts. Methods and Results— We examined the expression and functional role of β 3 -adrenoceptors in human coronary microarteries and their coupling to vasodilating nitric oxide (NO) and/or hyperpolarization mechanisms. The expression of β 3 -adrenoceptor mRNA and protein was demonstrated in extracts of human coronary microarteries. Immunohistochemical analysis revealed their exclusive localization in the endothelium, with no staining of vascular smooth muscle. In contractility experiments in which videomicroscopy was used, the nonspecific β-agonist isoproterenol and the β 3 -preferential agonist BRL37344 evoked an ≈50% relaxation of endothelin-1-preconstricted human coronary microarteries. Relaxations were blocked by the β 1 /β 2 /β 3 -adrenoceptor antagonist bupranolol but were insensitive to the β 1 /β 2 -adrenoceptor antagonist nadolol, confirming a β 3 -adrenoceptor-mediated pathway. Relaxation in response to BRL37344 was absent in human coronary microarteries devoid of functional endothelium. When human coronary microarteries were precontracted with KCl (thereby preventing vessel hyperpolarization), the relaxation to BRL37344 was reduced to 15.5% and totally abrogated by the NO synthase inhibitor l -ω-nitroarginine, confirming the participation of a NO synthase-mediated relaxation. The NO synthase-independent relaxation was completely inhibited by the Ca 2+ -activated K + channel inhibitors apamin and charybdotoxin, consistent with an additional endothelium-derived hyperpolarizing factor-like response. Accordingly, membrane potential recordings demonstrated vessel hyperpolarization in response to β 3 -adrenoceptor stimulation. Conclusions— β 3 -adrenoceptors are expressed in the endothelium of human coronary resistance arteries and mediate adrenergic vasodilatation through both NO and vessel hyperpolarization.

Recently, a functional, negatively inotropic, beta(3)-adrenoceptor was characterized in the human heart. Several studies now suggest that this receptor might play an important role in the pathophysiology of heart failure, by counterbalancing the effects of a beta(1)- and beta(2)-stimulation. Therefore, this review summarizes the rationale and effects of beta-adrenergic blockade in chronic heart failure and specifically addresses the question of the potential use of beta(3)-adrenoceptor antagonists in the treatment of heart failure and other pathophysiological conditions associated with a decreased cardiac contractility.

Background: In cardiovascular imaging, variations within and between observers, and between different acquisitions remain an important issue when interpreting in vivo data. Though there has recently been an increasing interest in ultra-high field MRI to characterize rodent models of cardiovascular diseases, reports concerning its reproducibility are scarce. The purpose of our work was to evaluate the intraobserver, interobserver and interexperiment variability of left ventricular (LV) mass and volumes measurements in mice using an 11.7T MRI scanner and to assess the validity of our results by comparing them with ex vivo measurements. Methods: 29 C57Bl6/J male mice aged 10-18 weeks were studied, including animals having previously undergone minimally invasive transverse aortic constriction. Imaging was performed on an 11.7 T MRI system (Biospec, Bruker, Germany). The LV systolic function was assessed from a stack of short-axis views obtained with a FLASH-cine sequence covering the entire ventricles. Using a dedicated software (SegmentTM, Medviso, Sweden), the following volumes (μl) were determined : end-diastolic, end-systolic and stroke volumes. LV ejection fraction (in %) and LV mass (mg) were subsequently deduced. Interobserver (n=24), intraobserver (n=24) and interexperiment (n=12) reproducibility were studied with the Bland and Altman method. LV masses obtained with the MRI were compared with ex vivo morphometric data. Results: Reproducibility was excellent for the LV mass and end-diastolic volume (EDV) (coefficient of variability - CoV - between 5,38 and 11,77%), good for end-systolic volume (ESV) (CoV between 15,24 and 16.81%) and moderate for data related to the smallest volumes, i.e. the stroke volume (SV) and ejection fraction (EF) (CoV between 14,73 and 20,93%). Importantly, we demonstrated an excellent correlation between LV mass measurements by weighing or imaging, with a Pearson correlation (r) of 0.92. Conclusions: In our study, we show that the mouse LV systolic function can be longitudinally assessed on an 11.7T MRI scanner, with excellent reproducibility of LV mass and EDV and a good correlation of LV mass results with ex vivo morphometric measurements. However, we highlight the need to take into account some shortcomings when interpreting MRI data, like moderate reproducibility of very small volumes, focusing on parameters that are the most reproducible or using alternative sequences with better resolution.

Background —Contrary to β 1 - and β 2 -adrenoceptors, β 3 -adrenoceptors mediate a negative inotropic effect in human ventricular muscle. To assess their functional role in heart failure, our purpose was to compare the expression and contractile effect of β 3 -adrenoceptors in nonfailing and failing human hearts. Methods and Results —We analyzed left ventricular samples from 29 failing (16 ischemic and 13 dilated cardiomyopathic) hearts (ejection fraction 18.6±2%) and 25 nonfailing (including 12 innervated) explanted hearts (ejection fraction 64.2±3%). β 3 -Adrenoceptor proteins were identified by immunohistochemistry in ventricular cardiomyocytes from nonfailing and failing hearts. Contrary to β 1 -adrenoceptor mRNA, Western blot analysis of β 3 -adrenoceptor proteins showed a 2- to 3-fold increase in failing compared with nonfailing hearts. A similar increase was observed for Gα i-2 proteins that couple β 3 -adrenoceptors to their negative inotropic effect. Contractile tension was measured in electrically stimulated myocardial samples ex vivo. In failing hearts, the positive inotropic effect of the nonspecific amine isoprenaline was reduced by 75% compared with that observed in nonfailing hearts. By contrast, the negative inotropic effect of β 3 -preferential agonists was only mildly reduced. Conclusions —Opposite changes occur in β 1 - and β 3 -adrenoceptor abundance in the failing left ventricle, with an imbalance between their inotropic influences that may underlie the functional degradation of the human failing heart.

Hypercholesterolemia is a central pathogenic factor of endothelial dysfunction caused in part by an impairment of endothelial nitric oxide (NO) production through mechanisms that remain poorly characterized. The activity of the endothelial isoform of NO synthase (eNOS) was recently shown to be modulated by its reciprocal interactions with the stimulatory Ca2+–calmodulin complex and the inhibitory protein caveolin. We examined whether hypercholesterolemia may reduce NO production through alteration of this regulatory equilibrium. Bovine aortic endothelial cells were cultured in the presence of serum obtained from normocholesterolemic (NC) or hypercholesterolemic (HC) human volunteers. Exposure of endothelial cells to the HC serum upregulated caveolin abundance without any measurable effect on eNOS protein levels. This effect of HC serum was associated with an impairment of basal NO release paralleled by an increase in inhibitory caveolin–eNOS complex formation. Similar treatment with HC serum significantly attenuated the NO production stimulated by the calcium ionophore A23187. Accordingly, higher calmodulin levels were required to disrupt the enhanced caveolin–eNOS heterocomplex from HC serum–treated cells. Finally, cell exposure to the low-density lipoprotein (LDL) fraction alone dose-dependently reproduced the inhibition of basal and stimulated NO release, as well as the upregulation of caveolin expression and its heterocomplex formation with eNOS, which were unaffected by cotreatment with antioxidants. Together, our data establish a new mechanism for the cholesterol-induced impairment of NO production through the modulation of caveolin abundance in endothelial cells, a mechanism that may participate in the pathogenesis of endothelial dysfunction and the proatherogenic effects of hypercholesterolemia.

Background It remains incompletely understood whether patients with transfusion related cardiac iron overload without signs of heart failure exhibit already subclinical alterations of systolic left ventricular (LV) dysfunction. Therefore we performed a comprehensive evaluation of systolic and diastolic cardiac function in such patients using tagged and phase-contrast CMR. Methods 19 patients requiring regular blood transfusions for chronic anemia and 8 healthy volunteers were investigated using cine, tagged, and phase-contrast and T2* CMR. LV ejection fraction, peak filling rate, end-systolic global midventricular systolic Eulerian radial thickening and shortening strains as well as left ventricular rotation and twist, mitral E and A wave velocity, and tissue e' wave and E/e' wave velocity ratio, as well as isovolumic relaxation time and E wave deceleration time were computed and compared to cardiac T2*. Results Patients without significant iron overload (T2* > 20 ms, n = 9) had similar parameters of systolic and diastolic function as normal controls, whereas patients with severe iron overload (T2* < 10 ms, n = 5), had significant reduction of LV ejection fraction (54 ± 2% vs. 62 ± 6% and 65 ± 6% respectively p < 0.05), of end-systolic radial thickening (+6 ± 4% vs. +11 ± 2 and +11 ± 4% respectively p < 0.05) and of rotational twist (1.6 ± 0.2 degrees vs. 3.0 ± 1.2 and 3.5 ± 0.7 degrees respectively, p < 0.05) than patients without iron overload (T2* > 20 ms) or normal controls. Patients with moderate iron overload (T2* 10-20 ms, n = 5), had preserved ejection fraction (59 ± 6%, p = NS vs. pts. with T2* > 20 ms and controls), but showed reduced maximal LV rotational twist (1.8 ± 0.4 degrees). The magnitude of reduction of LV twist (r = 0.64, p < 0.001), of LV ejection fraction (r = 0.44, p < 0.001), of peak radial thickening (r = 0.58, p < 0.001) and of systolic (r = 0.50, p < 0.05) and diastolic twist and untwist rate (r = -0.53, p < 0.001) in patients were directly correlated to the logarithm of cardiac T2*. Conclusion Multiple transfused patients with normal ejection fraction and without heart failure have subclinical alterations of systolic and diastolic LV function in direct relation to the severity of cardiac iron overload. Among all parameters, left ventricular twist is affected earliest, and has the highest correlation to log (T2*), suggesting that this parameter might be used to follow systolic left ventricular function in patients with iron overload.

Background In cardiovascular research, there is an increasing interest in high-field MRI to characterize cardiac anatomy and function in small rodents. However, data on reproducibility of the method are scarce. Our aim was to evaluate the intra-observer, inter-experiment and inter-observer variability of left ventricular (LV) mass and volumes measurements in mice using an 11.7T MRI scanner. Methods Seven 10 weeks-old C57Bl6J male mice were studied, including 4 animals with a surgical transverse aortic constriction in order to produce cardiac hypertrophy. 3 were sham (control) mice. During the entire procedure, animals were anaesthetized with Isoflurane 1-3%, in a temperature-controlled setting. Scan were retrospectively gated for electrocardiogram (ECG) and respiration. Imaging was performed on a 11.7 Tesla Bruker MR scanner. Cardiac scout images were obtained in the conventional planes with a tripilot sequence. A 2D cine FLASH sequence was applied to acquire a set of 7 contiguous short axis images covering the entire ventricles, perpendicular to the LV long axis. One day after the procedure, mice were scanned again under the same conditions. The LV systolic function was assessed from each stack of images by tracing epicardial and endocardial borders, including papillary muscles, on the Segment software (Medviso, Sweden). End-diastolic (EDV), end-systolic (ESV) and stroke volume (SV) were determined (µl). LV ejection fraction (EF, in %) and LV mass (mg) were subsequently deduced. One stack of images was analyzed twice by the same person, and once by an independent observer. Results Accurate quantitative data were obtained in all animals. The Table 1 lists the mean ± SD values and the Bland-Altman and Pearson analysis results. The best reproducibility was obtained for the measurements of LV mass and EDV, with a coefficient of variability (Cov) between 1.70 and 12%. More variation was found in ESV measurement (CoV 1-70-22.40%). Results for SV and EF were the less reproducible, with a CoV between 14.52 and 31.45%. The Pearson correlation coefficient indicates good correlation between all methods for all parameters (r square between 0.81 and 0.99), except for the SV, particularly in terms of inter-experiment reproducibility (r square =0.03). Conclusions In our hands, reproducibility was excellent for LV mass and EDV, good for ESV and EF to al esser extent, and more limited for the stroke volume, with a bad inter-observer correlation. This highlights the need to interpret our results by taking into account these limitations, focusing on more reproducible parameters when interpreting data.

IntroductionIn cardiovascular research, there has recently been an interest in ultra-high field MRI to characterize cardiac anatomy and function in rodents. However, reports on the accuracy of the method are scarce. The purpose of our work was to evaluate left ventricular (LV) systolic function in a mouse model of cardiac hypertrophy using an 11.7T MRI machine and to assess the validity of our results by comparing them with ex vivo measurements.Methods24 C57Bl/6J mice were studied, including 11 animals having undergone a surgical transverse aortic constriction (TAC) and 13 sham animals. Imaging was performed on a 11.7 Tesla Bruker MR scanner. The LV systolic function was assessed from a stack of 1mm thick short-axis views obtained with a FLASH-cine sequence covering the entire ventricles. Using a dedicated software (SegmentTM, Medviso, Sweden), the following volumes (μl) were determined: end-diastolic, end-systolic and stroke volumes. LV ejection fraction (in %) and LV mass (mg) were subsequently deduced. One week after, mice were sacrificed and their LV mass and tibial length (TL) were measured.ResultsAs expected, LV mass was significantly higher in the TAC group. When using the previously validated LV mass/tibial length ratio (LV/TL), sham mice showed a ratio of 4.65±0.09mg/mm and 3.83±0.11mg/mm for morphometric and MRI measurements respectively, and TAC mice showed a ratio of 6.50±0.40 and 5.39±0.28 respectively (p

Methods Seventeen patients (8 M, 9 F, 25 ± 9 years) who underwent multiple transfusions for a chronic hematopathy (12 thalassemia major, 4 aplastic anemias, 1 sickle cell anemia), but who did not have any overt cardiac disease, and 2 normal volunteers underwent MR assessment of T2* times using a multi-echo gradient echo sequence to estimate iron content in the liver and heart. These parameters were correlated to LV volumes and ejection fraction measured using SSFP and regional circumferential shortening strain, and apical rotation and twist measured using tagged images with HARP analysis.