Ali Houeijeh

Maternal PUFA ω-3 Supplementation Prevents Neonatal Lung Injuries Induced by Hyperoxia in Newborn Rats.

Bronchopulmonary dysplasia (BPD) is one of the most common complications of prematurity, occurring in 30% of very low birth weight infants. The benefits of dietary intake of polyunsaturated fatty acids ω-3 (PUFA ω-3) during pregnancy or the perinatal period have been reported. The aim of this study was to assess the effects of maternal PUFA ω-3 supplementation on lung injuries in newborn rats exposed to prolonged hyperoxia. Pregnant female Wistar rats (n = 14) were fed a control diet (n = 2), a PUFA ω-6 diet (n = 6), or a PUFA ω-3 diet (n = 6), starting with the 14th gestation day. At Day 1, female and newborn rats (10 per female) were exposed to hyperoxia (O2, n = 70) or to the ambient air (Air, n = 70). Six groups of newborns rats were obtained: PUFA ω-6/O2 (n = 30), PUFA ω-6/air (n = 30), PUFA ω-3/O2 (n = 30), PUFA ω-3/air (n = 30), control/O2 (n = 10), and control/air (n = 10). After 10 days, lungs were removed for analysis of alveolarization and pulmonary vascular development. Survival rate was 100%. Hyperoxia reduced alveolarization and increased pulmonary vascular wall thickness in both control (n = 20) and PUFA ω-6 groups (n = 60). Maternal PUFA ω-3 supplementation prevented the decrease in alveolarization caused by hyperoxia (n = 30) compared to PUFA ω-6/O2 (n = 30) or to the control/O2 (n = 10), but did not significantly increase the thickness of the lung vascular wall. Therefore, maternal PUFA ω-3 supplementation may protect newborn rats from lung injuries induced by hyperoxia. In clinical settings, maternal PUFA ω-3 supplementation during pregnancy and during lactation may prevent BPD development after premature birth.

Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs

Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n-3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E− (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR (n = 8, p < 0.001). Incubation of vascular rings with EPA (100 µM) caused a maximum relaxation of 60% in the E+ (n = 6), whereas vessel tone did not change in the E− (n = 6, p < 0.001). The vascular effects of EPA were significantly decreased in LNA E+ (n = 6). Incubation with DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN.

French national survey on infective endocarditis and the Melody™ valve in percutaneous pulmonary valve implantation

BACKGROUND Percutaneous pulmonary valve implantation (PPVI) is a routine treatment for dysfunctional right ventricular outflow tract. Infective endocarditis (IE) is a major concern. AIM To report French experience with the Melody™ valve (Medtronic Inc., Minneapolis, MN, USA). METHODS All patients who underwent PPVI were recorded in a multicentre French national survey. Demographic and procedural data were collected from patients with IE. Bacterial identification, diagnostic tools and outcome were recorded. RESULTS Forty-five cases of IE were diagnosed in 43 patients. The cumulative IE incidence was 11.8% (95% confidence interval [CI] 8.5-15.9). The annualized IE incidence was 3.6% (95% CI 0-4.8). Freedom from IE was 96.3% and 85.8% at 12 months and 60 months, respectively. IE incidence did not change during the study period. The mean interval between PPVI and IE was 2.6±2.1 years (range, 5 days to 7.3 years). Fifteen patients with IE required intravenous antibiotics only. Seven patients had early interventional cardiac catheterization to relieve severe right ventricular outflow tract obstruction. Twenty-four patients had surgical valve replacement (six urgently; nine semi-urgently; nine electively). Staphylococcus aureus IE required surgery in all but one patient. Three patients died before any treatment. Three additional patients died, giving a mortality rate of 14%. Global survival in the total cohort of patients who received a Melody valve was excellent (96.5% at 5 years). When comparing survival curves between the IE and non-IE groups, death and cardiovascular events were statistically significantly higher in the IE group (log-rank P<0.0001). CONCLUSION Melody valve IE is a severe complication following PPVI. The annualized IE incidence in this cohort was similar to rates reported in other studies. With rapid diagnosis and adequate treatment, outcome has improved, and unfavourable outcome is mainly associated with S. aureus.

Vasodilator effects of dehydroepiandrosterone (DHEA) on fetal pulmonary circulation: An experimental study in pregnant sheep

Persistent pulmonary hypertension (PPHN) remains a severe complication of the transition to extra-uterine life with significant morbidity and mortality in the newborns. Dehydroepiandrosterone (DHEA) represents a new pharmacological agent with vascular effects, including improvement of PPHN in several animal models. We hypothesized that DHEA could decrease pulmonary vascular resistance (PVR) in the pulmonary circulation of fetal sheep. We studied the effect of intravenous infusion of DHEA in fetal lambs using chronically instrumented sheep at 128 days of gestation. PVR was computed before and after intravenous infusion of increasing doses of DHEA. We assessed pre-treatment by L-nitroarginine, an inhibitor of NO production. Blood gases and doses of DHEA were measured in both sheep and fetus before/after DHEA infusion. Intravenous infusion of DHEA had a vasodilator effect with a significant decrease in PVR (respectively -11%, -14% and -36% after infusion of 6, 12 and 24 mg DHEA, p<0.01) without damaging effects on systemic circulation or on blood gases. The inhibitory effect of pre-treatment with L-nitroarginine resulted in a significant increase in PVR. We demonstrated a potent vasodilator effect of DHEA on fetal pulmonary circulation without deleterious effects. DHEA might represent a new treatment for PPHN.

Transcatheter closure of large atrial septal defects (ASDs) in symptomatic children with device/weight ratio ≥1.5

BACKGROUND Atrial septal defects (ASDs) can be symptomatic in small children in cases of co-morbidities. Transcatheter closure remains controversial for large defects in small children. OBJECTIVE To describe transcatheter closure of ASDs in children with device/weight ratio ≥1.5. METHODS We retrospectively studied between January 2000 and January 2016 all cases of percutaneous ASD closure with device/weight ratio ≥1.5 in 6 European centres. RESULTS Forty patients were included with female/male ratio of 1.2. Median age and weight were 30.9 months (4.1-102.0) and 11.0 kg respectively (3.8-19.0). Median device size/weight ratio was 1.7 (1.5-2.3). All patients were symptomatic, with pulmonary hypertension in 13 (33%). Procedures were performed under general anesthesia or light sedation (n = 4), with transthoracic (n = 25) or transesophageal echocardiography (n = 15) guidance. Balloon stretched diameter (n = 32) was larger than the echocardiographic diameter (19 versus 15 mm, R = 0.6; p < 0.001). Deficient rims other than the anterior-superior one were found in 33% of cases. Device implantation was successful in 39 patients (97.5%). Minor complications occurred in 10% of cases, whereas severe complications rate was 5%: Complete atrioventricular block in one patient that resolved after surgical extraction of the device and thrombosis in the inferior vena cava in one patient. During a median follow-up of 52 months, there was no residual shunt. No case of erosion or embolization was reported and pulmonary hypertension resolved in all patients. CONCLUSION Percutaneous closure of large ASD in small and symptomatic children is feasible and allows clinical improvement with acceptable rate of complications in high risk population.

Mise au pointCathétérisme interventionnel dans les cardiopathies congénitalesInterventional cardiac catheterization in congenital heart disease

Interventional cardiac catheterization has a major place in the management of congenital heart disease. Since the Rashkind atrioseptostomy in mid-1960s, many techniques have been developed. For some, it is necessary to close a cardiac or extracardiac shunt using occluder (double disc system, plug, coil…): closure of atrial septal defect, ventricular septal defect or patent arterial duct. For others, it is necessary to treat a valvular or vascular stenosis using a balloon catheter: dilatation of the pulmonary or the aortic valve, dilatation of aortic coarctation. For vascular stenosis, balloon angioplasty may be associated with stent implantation. Moreover, since more than 10 years, valve implantation can be performed: initially for pulmonic valve (the Melody™ valve from Medtronic or the Sapien™ valve from Edwards Lifesciences); but probably, most of the valves in the future could be implanted using appropriate tools and hybrid techniques combining cardiac catheterization and surgery. All these techniques were developed because of progress in fluoroscopy, and more recently association of different imaging techniques (echocardiography, MRI and CT) provides more information about the true anatomy. Interventional cardiac catheterization will continue to increase with use of new tools as 3D printing, tissue engineering and nano-techniques. It seems that from correction with open-heart surgery, many lesions could be repaired in future by hybrid techniques without opening the heart.

Lung liquid clearance in preterm lambs assessed by magnetic resonance imaging

Background:Postnatal adaptation requires liquid clearance and lung aeration. However, their relative contribution to the expansion of functional residual capacity (FRC) has not been fully investigated. We studied evolution of lung liquid removal and lung aeration after birth in preterm lambs.Methods:Lung liquid content and lung volume were assessed at birth and every 30 min over 2 h using magnetic resonance imaging (MRI) in three groups of lambs delivered by cesarean: preterm, late preterm, and late preterm with antenatal steroids. Lung function and mechanics of the respiratory system were also measured.Results:Lung liquid content increased by approximately 30% in the preterm group (P < 0.05), whereas it did not change significantly in the late preterm lambs. Antenatal steroids induced a 50% drop in the lung liquid content (P < 0.05). Total lung volume increased in all groups (P < 0.05) but was higher in the late preterm + steroids group relative to other groups (P < 0.05). Compliance and resistances of the respiratory system were significantly correlated with lung liquid content (P < 0.05).Conclusion:FRC expansion results mainly from an increase in lung volume rather than a decrease in lung liquid in preterm and late preterm lambs. Antenatal steroids promote FRC expansion through increases in lung volume and liquid clearance.

0398: Transcatheter closure of traumatic induced VSD

Traumatic induced VSD is a rare but serious disease because of the acute hemodynamic changes. We reported one center experience in the interventional catheterization closure of traumatic induced VSD during the last ten years. We had 3 patients with four VSD. Mean age was 60 (40-71) years. VSD was muscular secondary to external trauma in one patient, and to transapical transcatheter replacement of both of the aortic and mitral valves in the second. Last patient had membranous and muscular VSD post Ross-Konno intervention. All patients had acute congestive heart failure. All procedures were performed under general anesthesia and transesophageal echocardiography control. Arteriovenous loop was always used to introduce the delivery sheath to the left ventricle. VSDs diameter was evaluated by echography and ranged from 9 to 13mm. Device diameter was chosen 1 to 2mm over the echo-graphic measures. Multiple devices were used (Amplatzer® septal occluder, Amplatzer® muscular VSD occluder, Occlutech® Figulla septal occluder). Mean procedures time was 113 (100-145) min, and mean irradiation dose was 160 (103-203) Gycm2. Non significant residual shunt was observed in all patients, but the heart failure was resolved in all. Complications were registered in three procedures: transient hemolytic anemia, severe bradycardia, tricuspid cordage rupture and groin hematoma. Conclusion Traumatic VSD closure is required because of the acute hemo-dynamic changes. Trancatheter closure is effective. Complications are frequents because of the critical clinical status.

0076: Transcatheter closure of the arterial duct with the Occlutech PDA occluder

Purpose Transcatheter closure of the arterial duct using the Occlutech PDA occluder. Methods and results From March 2013 to April 2015, 16 patients underwent percutaneous arterial duct closure with the new Occlutech PDA occluder. There were 10 females and 6 males. All patients had significant L-to-R shunt with enlarged left ventricle. At implantation, the mean age was 87 months (median 35 months) and mean weight was 16±11kg (7.2 to 54kg). The procedure was realized under local anaesthesia. Size of the duct was 2.96±0.94mm (range 1.7 to 5.5mm) on angiography. According to Krichenko classification of PDA, ducts were: type A (n=14), Type B (n=1) and type E (n=1). The systolic pulmonary artery pressure was 43±17mmHg (range 24 to 91mmHg). Implantation succeeded in all. Closure was performed by the standard 4/6mm occluder (n=8), the standard 6/8mm occluder (n=3), the standard 5/7mm occluder (n=3), the standard 3.5/ 5mm (n=1) and the standard 8/10mm occluder (n=1) using a 6 or 7 F delivery sheath. After implantation, trivial shunt was noticed on angiography in 12 patients, 4 had no shunt. The fluoroscopic time was 6.5±8.7 minutes and radiation dose 6.0±4 Gycm2. After closure, femoral thrombosis was noticed in 2 patients but resolved completely under heparin therapy. On control Doppler echocardiography (1 to 18 months), duct was closed in all patients but one with only one month follow-up. No obstruction of the left pulmonary artery or isthmic stenosis was noticed. Conclusions Percutaneous closure of PDA with the new Occlutech PDA occluder is safe and effective. The device is easy to handle and there is no learning curve for operators using the classic Amplatzer duct occluder. Further studies with longer follow-up are necessary to confirm these good results.

0323: Mid-term follow-up and quality of life in patients after Fontan surgery

Background The Fontan procedure (atriopulmonary Fontan) and total cavo-pulmonary connection are designed to treat univentricular heart. Whereas peri-operative mortality has declined, the current challenge is long-term outcome. Objective To evaluate the outcome and quality of life of survivors with Fontan circulation. Methods This retrospective monocentric study aimed patients who had follow-up after Fontan surgery at the University Hospital of Lille. Data were collected on medical records. The quality of life was evaluated between June and October 2014 by two scales: Paediatric Quality of Life Inventory TM (PedsQL) before 26 years of age and Medical Outcome Study Short Form 36 (MOS SF 36) after 26 years. Results Among 96 patients who underwent Fontan procedure, median follow-up was 9.6 (6.1-12.5) years after the last intervention. Nine-year global survival was 93%. 95% of patients had total cavo-pulmonary connection and 5% had atrio-pulmonary connection. Arrhythmia occurred in 27.1%, single ventricle dysfunction in 87.4%, leak of the atrio-ventricular valve in 58.9%. Protein-losing enteropathy affected 4.2% of patients and thromboembolic events appeared in 17.7%. Total score of quality of life was 66.5% according to the PedsQL and 62.5% to the MOS SF36. Conclusion This French cohort of survivors with Fontan circulation has the same initial characteristics than which described in the literature. The level of quality of life was comparable to general population. The question of global rehabilitation of these patients must be raised.