[Congenital heart disease: from childhood to adulthood]. / Cardiopathie congénitale: de l'enfance à l'âge adulte.

With the improvement of congenital heart surgery, most children with congenital heart disease will survive into adulthood with a good quality of life. Regular cardiac follow-up is recommended for all patients. The adolescent period coincides often with medium and long term consequences and complications and repeat surgery or catheter interventions might be needed. It is therefore of prime importance to begin the transition process early and to pursue it well into adulthood. We have elaborated a formal transition program adapted to youngsters with congenital heart disease.

[Adults with congenital heart diseases: a growing population, a multidisciplinary approach]. / Cardiopathies congénitates de l'âge adulte: nouvelle population de patients, prise en charge multidisciplinaire.

Untill recently, congenital heart disease was considered as a childhood's disease. With improvement in pediatric survival, adults with a congenital heart disease (ACHD) represent an emerging group of patients who need specialized medical care. In 2010, the ESC published newguidelines on global and specific management of adults with congenital heart disease. ACHD centers organize appropriate medical care for these patients, promote specialist training and national scientific research in collaboration with other national ACHD centers.

[New treatments of pediatric pulmonary hypertension]. / Nouveaux traitements de l'hypertension pulmonaire en pédiatrie.

Pulmonary arterial hypertension is a serious condition, with an estimated prevalence of 4 children over a million. Symptoms of this condition are not specific, leading to a potential delay in the diagnosis. Treatment of pediatric pulmonary hypertension is currently based on adult guidelines, using new targeted therapies, separated in 3 main categories: Endothelin receptor antagonists, prostacyclin and analogues, and phosphodiesterase type 5 inhibitors. These therapies improve symptoms and survival, but neither of them can cure the condition. Various new molecules are being currently tested in children or in development, offering hope to further improve the prognosis of pulmonary arterial hypertension.

Pulmonary arterial hypertension: a comparison between children and adults.

The characteristics of pulmonary arterial hypertension (PAH), including pathology, symptoms, diagnosis and treatment are reviewed in children and adults. The histopathology seen in adults is also observed in children, although children have more medial hypertrophy at presentation. Both populations have vascular and endothelial dysfunction. Several unique disease states are present in children, as lung growth abnormalities contribute to pulmonary hypertension. Although both children and adults present at diagnosis with elevations in pulmonary vascular resistance and pulmonary artery pressure, children have less heart failure. Dyspnoea on exertion is the most frequent symptom in children and adults with PAH, but heart failure with oedema occurs more frequently in adults. However, in idiopathic PAH, syncope is more common in children. Haemodynamic assessment remains the gold standard for diagnosis, but the definition of vasoreactivity in adults may not apply to young children. Targeted PAH therapies approved for adults are associated with clinically meaningful effects in paediatric observational studies; children now survive as long as adults with current treatment guidelines. In conclusion, there are more similarities than differences in the characteristics of PAH in children and adults, resulting in guidelines recommending similar diagnostic and therapeutic algorithms in children (based on expert opinion) and adults (evidence-based).

Novel approach to mitral valve repair in childhood dilated cardiomyopathy.

Evidence is mounting that mitral valve repair can improve symptoms in adults with dilated cardiomyopathy. Data is currently lacking for children with dilated cardiomyopathy and options for annuloplasty are limited in children. We report on the successful management of a 21 month-old child in heart failure from dilated cardiomyopathy and severe mitral regurgitation. The echocardiogram showed severely dilated left heart cavities, severe mitral regurgitation from a dilated annulus (23 mm, Z-score 1.74) with discrete anterior leaflet tethering, and moderate systolic dysfunction. The mitral valve was repaired using a 16 mm Bioring Kalangos biodegradable annuloplasty ring. The patient was extubated on the third postoperative hour and discharged on the fifth postoperative day with trivial mitral regurgitation and a 5 mmHg mean transvalvular gradient. At 12 months, the patient is in NYHA class I and presents trivial central mitral regurgitation without any transmitral gradient. This represents the first report in successfully managing a child with dilated cardiomyopathy with mitral regurgitation using a novel biodegradable annuloplasty ring, which has the potential to durably remodel the mitral annulus and grow with the patient.

Decreased bone turnover in children and adolescents with well controlled type 1 diabetes.

AIM: Osteoporosis is a common long-term complication of type 1 diabetes (T1DM). We aimed to determine whether bone mineral density (BMD) and turnover are already altered during childhood. PATIENTS AND METHODS: We recruited 27 T1DM children and 32 controls (age 10.5 +/- 2.5 yr.) and measured BMD (dual-energy x-ray absorptiometry); bone biomarkers levels (osteocalcin: OC; procollagen type 1 propeptides amino-terminal: PINP; crosslinking telopeptides of type 1 collagen C-terminal: CTX), glycated hemoglobin (HbA1c), dietary intake and physical activity. RESULTS: Patients with T1DM had lower levels of OC (70.3 +/- 3.3 vs 105.3 +/- 6.8), PINP (556.4 +/- 47.6 vs 716.3 +/- 53.8), CTX(0.97 +/- 0.07 vs 1.20 +/- 0.08), physical activity, and calcium intake. Biomarkers were negatively correlated with HbA1c. Though, BMD was similar among groups and not related to HbA1c, disease duration, physical activity or dietary intakes. CONCLUSIONS: Bone turnover is altered in T1DM children, whereas BMD remains normal during growth. Physical activity and optimal calcium intakes may improve bone metabolism and delay osteoporosis.

Biodegradable mitral annuloplasty for congenital ischemic mitral regurgitation.

An anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is associated with ischemic mitral regurgitation through a combination of papillary muscle ischemia or permanent fibrosis, left ventricular free wall ischemic dyskinesis and left ventricular dilatation. We report the successful management of a 27-month-old girl with ALCAPA and severe mitral regurgitation using a biodegradable mitral annuloplasty ring. It could represent a novel tool for mitral valve repair in ALCAPA-associated ischemic mitral regurgitation.

[Pulmonary hypertension associated with congenital heart disease]. / Hypertension artérielle pulmonaire des cardiopathies congénitales.

INTRODUCTION: Congenital heart diseases are among the most common congenital malformations at birth with an incidence of 8/1,000 live births. These defects are characterized by a heterogeneous group of abnormal defects and connections between the cardiac chambers and vessels with different haemodynamic consequences and hence, varying need for follow-up and interventions. The most common forms are congenital cardiac shunts (i.e.: ventricular septal defects, atrial septal defects, patent ductus arteriosus) that account for almost 60% of the malformations. STATE OF THE ART: Pulmonary hypertension remains a major complicating factor of many types of congenital heart disease characterized by a systemic to pulmonary shunt either by causing increased morbidity and mortality during or immediately after surgical repair, or even preventing complete repair for those with advanced pulmonary vascular disease. Similarities in histological lesions between congenital heart disease and idiopathic pulmonary arterial hypertension suggest similarities in pathobiological pathways and thus pulmonary arterial hypertension associated with congenital cardiac shunt has been classified in the group 1 of the classification of Venice. Even if these complex mechanisms are not completely elucidated, the role of hemodynamics (shear stress) in the development of pulmonary vascular disease has been clearly demonstrated. PERSPECTIVES AND CONCLUSION: Until recently, patients with advanced pulmonary vascular disease following congenital systemic to pulmonary shunt had no specific treatment and were managed empirically. Because of the similarities with idiopathic pulmonary arterial hypertension the use of novel therapies suggest new therapeutic possibilities for these patients. Randomized controlled trials are definitely needed to evaluate the safety and efficacy of these therapies in this very particular group of patients, both in the short and long term.

Haemodynamic characterisation and heart catheterisation complications in children with pulmonary hypertension: Insights from the Global TOPP Registry (tracking outcomes and practice in paediatric pulmonary hypertension).

BACKGROUND: The TOPP Registry has been designed to provide epidemiologic, diagnostic, clinical, and outcome data on children with pulmonary hypertension (PH) confirmed by heart catheterisation (HC). This study aims to identify important characteristics of the haemodynamic profile at diagnosis and HC complications of paediatric patients presenting with PH. METHODS AND RESULTS: HC data sets underwent a blinded review for confirmation of PH (defined as mean pulmonary arterial pressure ≥ 25 mmHg, pulmonary capillary wedge pressure ≤ 12 mmHg and pulmonary vascular resistance index [PVRI] of >3 WU × m(2)). Of 568 patients enrolled, 472 who fulfilled the inclusion criteria and had sufficient data from HC were analysed. A total of 908 diagnostic and follow-up HCs were performed and complications occurred in 5.9% of all HCs including five (0.6%) deaths. General anaesthesia (GA) was used in 53%, and conscious sedation in 47%. Complications at diagnosis were more likely to occur if GA was used (p=0.04) and with higher functional class (p=0.02). Mean cardiac index (CI) was within normal limits at diagnosis when analysed for the entire group (3.7 L/min/m(2); 95% confidence interval 3.4-4.1), as was right atrial pressure despite a severely increased PVRI (16.6 WU × m(2,) 95% confidence interval 15.6-17.76). However, 24% of the patients had a CI of <2.5L/min/m(2) at diagnosis. A progressive increase in PVRI and decrease in CI was observed with age (p<0.001). CONCLUSION: In TOPP, haemodynamic assessment was remarkable for preserved CI in the majority of patients despite severely elevated PVRI. HC-related complication incidence was 5.9%, and was associated with GA and higher functional class.

Inhaled nitric oxide versus aerosolized iloprost in secondary pulmonary hypertension in children with congenital heart disease: vasodilator capacity and cellular mechanisms.

BACKGROUND: Inhaled nitric oxide (iNO) has been used to assess the vasodilator capacity of the pulmonary vascular bed in children with congenital heart disease and elevated pulmonary vascular resistance. Inhaled iloprost is a pulmonary vasodilator for the long-term treatment of pulmonary hypertension (PHT). Because these 2 vasodilators act through different pathways (release of cGMP or cAMP, respectively), we compared the pulmonary vasodilator capacity of each. METHODS AND RESULTS: A total of 15 children with congenital heart disease and PHT who had elevated pulmonary vascular resistance (preoperative, n=10; immediately postoperative, n=5) were first given 20 ppm of iNO for 10 minutes; then, after baseline values were reached again, they were given aerosolized iloprost at 25 ng. kg(-1). min(-1) for another 10 minutes. Finally, iNO and iloprost were given simultaneously for 10 minutes. With iNO, the pulmonary vascular resistance and systemic vascular resistance ratio decreased from 0.48+/-0.38 to 0.27+/-0.16 (P:<0.001). Similarly, iloprost decreased the ratio from 0.49+/-0.38 to 0.26+/-0.11 (P:<0.05). The combination had no additional effect on the resistance ratio. Plasma cGMP increased from 17.6+/-11.9 to 34.7+/-21.4 nmol/L during iNO (P:<0.01), and plasma cAMP increased from 55.7+/-22.9 to 65.1+/-21.2 nmol/L during iloprost inhalation (P:<0.05). CONCLUSIONS: In children with PHT and congenital heart disease, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through an increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone. Aerosolized iloprost might be an alternative to iNO for early testing of vascular reactivity and for the postoperative treatment of acute PHT.

[The contribution of molecular genetics to clinical cardiology: the example of hypertrophic cardiomyopathy]. / L'apport de la génétique moléculaire en cardiologie clinique: l'exempte de la cardiomyopathie hypertrophique.

Recent advances in molecular genetics have resulted in the identification of pathogenic mutations in a number of genes which cause hypertrophic cardiomyopathy (HCM). In order to integrate this increasing genetic knowledge of HCM into the cardiology clinic, we offer all patients and their families diagnosis and genetic counselling based on these current data. In addition, within the framework of a multidisciplinary project between the Divisions of Medical Genetics, Cardiology and Pediatric Cardiology of the University Hospitals of Geneva, we have developed a resequencing array enabling rapid molecular diagnosis of HCM. Data from this study will enhance our understanding of the aetiology of HCM, and improve our knowledge of genotype-phenotype correlations. This information will enable us to develop new therapeutic and preventive concepts, with the aim of tailoring therapies to the specific genetic variant of each patient and its family.

Inhaled nitric oxide to test the vasodilator capacity of the pulmonary vascular bed in children with long-standing pulmonary hypertension and congenital heart disease.

Nitric oxide-induced vasodilator capacity greatly varies among children with pulmonary hypertension and elevated vascular resistance. The decline of this selective response seems to parallel the progression of established vascular disease and thus may be helpful for the selection of patients for operation.

Aortic valve repair by cusp extension with the use of fresh autologous pericardium in children with rheumatic aortic insufficiency.

OBJECTIVES: Our goal was to evaluate the midterm results of aortic valve repair by a more sophisticated tailoring of cusp extension-taking into account the dimensions of the native aortic cusps-with the use of fresh autologous pericardium. PATIENTS AND METHODS: Forty-one children who had severe rheumatic aortic insufficiency (mean age 11.5 +/- 2.7 years) underwent aortic valve repair by means of this cusp extension technique over a 5-year period. Twenty-four of them underwent concomitant mitral valve repair for associated rheumatic mitral valve disease. All children were then followed up by transthoracic echocardiography before discharge, at 3 and 6 months after the operation, and at yearly intervals thereafter. RESULTS: Follow-up was complete in all patients and ranged from 3 months to 5 years (median 3 years). No operative and no early postoperative deaths occurred. Only 1 patient died, 9 months after the operation, of septicemia and multiple organ failure. Actuarial survival was 97% at 1 year and has remained unchanged at 3 years. On discharge, the degree of aortic insufficiency was grade 0 for 27 children and grade I for 14. Exacerbation of aortic insufficiency from grade I to grade II was observed in only 1 patient, and none of the children required reoperation for aortic insufficiency during the follow-up period. Mean peak systolic aortic valve gradients at discharge were lower than preoperative values (P =.04), and no significant increase in the peak systolic transvalvular gradient was detected thereafter during the follow-up period. Mean left ventricular dimensions were significantly reduced at discharge when compared with preoperative values (P <.0001). CONCLUSIONS: Functional results of aortic valve repair with cusp extension using fresh pericardium have been satisfactory at medium term, particularly in children with a small aortic anulus at the time of initial repair, because the expansion potential of fresh autologous pericardium is equivalent to that of the growing sinotubular junction and aortic anulus diameters.

Inhaled nitric oxide differentiates pulmonary vasospasm from vascular obstruction after surgery for congenital heart disease.

OBJECTIVE: To evaluate whether a trial of inhaled nitric oxide (NO) differentiates reversible pulmonary vasoconstriction from fixed anatomic obstruction to pulmonary blood flow after surgery for congenital heart disease in patients at risk for pulmonary hypertension. DESIGN: Prospective cohort study. SETTING: Tertiary care children's hospital. PATIENTS: 15 neonate and infants with elevated pulmonary artery or right ventricular pressure or with clinical signs suggestive of high pulmonary vascular resistance in the early postoperative period following repair of congenital heart disease. INTERVENTION: 30-min trial of 40 ppm inhaled NO. RESULTS: 5 patients responded to inhaled NO, 2 patients were weaned from extracorporeal support with NO. Four were maintained on continuous inhaled NO for 3 to 5 days. All the responders survived. Ten patients did not respond to NO. An important anatomic obstruction was found with echocardiography or angiography in all 10 patients. Reintervention was performed in 6/10 (4 stent placement, 1 balloon angioplasty of pulmonary arteries and 1 revision of systemic to pulmonary shunt). Six of the nonresponders died. CONCLUSION: A trial of inhaled NO after cardiac surgery in neonates and infants may be useful to differentiate reversible pulmonary vasoconstriction from fixed anatomic obstruction and may provide useful information if temporary support with extracorporeal membrane oxygenation is considered. Failure to respond to inhaled NO should prompt further investigations to rule out a residual obstruction.

Relief of severe pulmonary hypertension after closure of a large ventricular septal defect using low dose inhaled nitric oxide.

A 16-month-old girl developed severe pulmonary hypertension after closure of a large ventricular septal defect. All conventional therapeutic measures failed; an attempt to add nitric oxide at a continuous low dose to the inspired gas allowed resolution of pulmonary hypertension and low cardiac output. This report documents that continuous inhalation of low dose nitric oxide is capable of selective resolution of pulmonary hypertension following cardiac surgery for a large septal defect in a child. This suggests that a transient dysfunction in the release of nitric oxide by the pulmonary endothelial cell is responsible for the vasoconstriction.

Leaflet's free edge suspension for correction of aortic insufficiency associated with ventricular septal defect.

Aortic valve regurgitation in association with ventricular septal defect results from the mechanical effect of the ventricular septal defect, which primarily affects the free edge. The elongated free edge can be repaired by plicating it using several techniques designed to restore a normal geometry to the prolapsing aortic leaflet. We describe 4 cases in which aortic insufficiency was treated by a technique of plication that allows suspension of the free edge along a pericardial strip applied from one commissure to the other.

Aorticoright atrial tunnel.

Two unusual cases of aorticoright atrial tunnel are described. Both patients were referred to our institution for evaluation of a continuous heart murmur best heard along the right upper sternal border. Ascending aortography showed the tunnel taking its origin from the aortic root and entering the right atrium through a tortuous link. Both patients underwent surgical closure. In addition, a review of similar cases in the literature is presented.

Ascending aortic aneurysm associated with aortic insufficiency due to Takayasu's arteritis.

We report the case of a child with an ascending aortic aneurysm associated with aortic insufficiency. Histopathological examination of the ascending aorta and aortic valve showed findings in favor of Takayasu's arteritis, and subsequent evaluation of the entire aorta demonstrated the presence of multiple steno-occlusive lesions. This unusual clinical problem in the young population is discussed with regard to other eventual pathologies that should be taken into account in the differential diagnosis.

Treatment of a persistent postoperative chylothorax with somatostatin.

Chylothorax is a rare but potentially serious complication of pediatric cardiac operations. We report the case of a 4-month-old boy who underwent a Senning procedure for correction of D-transposition of the great vessels. A persistent postoperative chylothorax developed, necessitating continuous drainage, despite conservative treatment over 3 weeks. Thereafter, continuous somatostatin infusion for 14 days led to the reduction and finally cessation of chyle production. This treatment allowed early enteral feeding and avoided further surgical intervention.