A human importin-ß-related disorder: Syndromic thoracic aortic aneurysm caused by bi-allelic loss-of-function variants in IPO8.

Importin 8, encoded by IPO8, is a ubiquitously expressed member of the importin-ß protein family that translocates cargo molecules such as proteins, RNAs, and ribonucleoprotein complexes into the nucleus in a RanGTP-dependent manner. Current knowledge of the cargoes of importin 8 is limited, but TGF-ß signaling components such as SMAD1-4 have been suggested to be among them. Here, we report that bi-allelic loss-of-function variants in IPO8 cause a syndromic form of thoracic aortic aneurysm (TAA) with clinical overlap with Loeys-Dietz and Shprintzen-Goldberg syndromes. Seven individuals from six unrelated families showed a consistent phenotype with early-onset TAA, motor developmental delay, connective tissue findings, and craniofacial dysmorphic features. A C57BL/6N Ipo8 knockout mouse model recapitulates TAA development from 8-12 weeks onward in both sexes but most prominently shows ascending aorta dilatation with a propensity for dissection in males. Compliance assays suggest augmented passive stiffness of the ascending aorta in male Ipo8-/- mice throughout life. Immunohistological investigation of mutant aortic walls reveals elastic fiber disorganization and fragmentation along with a signature of increased TGF-ß signaling, as evidenced by nuclear pSmad2 accumulation. RT-qPCR assays of the aortic wall in male Ipo8-/- mice demonstrate decreased Smad6/7 and increased Mmp2 and Ccn2 (Ctgf) expression, reinforcing a role for dysregulation of the TGF-ß signaling pathway in TAA development. Because importin 8 is the most downstream TGF-ß-related effector implicated in TAA pathogenesis so far, it offers opportunities for future mechanistic studies and represents a candidate drug target for TAA.

Antithrombotic Therapy Duration after Patent Foramen Ovale Closure for Stroke Prevention: Impact on Long-Term Outcome.

Background: The optimal duration of antithrombotic therapy (ATT) after patent foramen ovale (PFO) closure remains under debate. This study sought to compare the clinical outcome of patients receiving antithrombotic agents for a short (6 months) versus extended (>6 months) period after the procedure. Methods: This was a retrospective cohort study using a propensity score matching analysis on 259 consecutive patients (131 males, 43 ± 10 years) undergoing PFO closure due to cryptogenic stroke, with complete follow-up (median duration of 10 [4-13] years). The outcome was compared between patients receiving short-term (Group short, N = 88) versus extended ATT (Group long, N = 171). Results: The PFO closure device was successfully implanted in all cases, with 3% of minor complications. After propensity score matching, there were no differences between Groups short and long in the rate of stroke (0.3 vs. 0.4% patient-year, p=1.00), bleeding (2 vs. 2% patient-year, p=0.17), and device thrombosis (0.3 vs. 0.1% patient-year; p=0.60). Univariate analysis showed that short-term ATT was not associated with an increased risk of recurrent stroke (HR: 1.271 [95% CI: 0.247-6.551], p=0.775) or prosthesis thrombus (HR: 0.50 [95% CI: 0.070-3.548], p=0.72). Kaplan-Meier analysis revealed similar overall survival in Group short and long (100 vs. 99 ± 1%, respectively; p=0.25). Conclusions: Short-term (6 months) ATT after PFO closure did not impair the clinical outcome, with a preserved low rate of recurrent stroke (0.3% patient-year) and device thrombosis (0.2% patient-year) at 10-year follow-up.

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

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

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

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

Liver and systemic hemodynamics in children with cirrhosis: Impact on the surgical management in pediatric living donor liver transplantation.

Cirrhosis in adults is associated with modifications of systemic and liver hemodynamics, whereas little is known about the pediatric population. The aim of this work was to investigate whether alterations of hepatic and systemic hemodynamics were correlated with cirrhosis severity in children. The impact of hemodynamic findings on surgical management in pediatric living donor liver transplantation (LT) was evaluated. Liver and systemic hemodynamics were studied prospectively in 52 children (median age, 1 year; 33 with biliary atresia [BA]). The hemodynamics of native liver were studied preoperatively by Doppler ultrasound and intraoperatively using invasive flowmetry. Portosystemic gradient was invasively measured. Systemic hemodynamics were studied preoperatively by Doppler transthoracic echocardiography and intraoperatively by using transpulmonary thermodilution. Hemodynamic parameters were correlated with Pediatric End-Stage Liver Disease (PELD) score and the histological degree of fibrosis (collagen proportionate area [CPA]). Cirrhosis was associated with a 60% reduction of pretransplant total liver flow (n = 46; median, 36 mL/minute/100 g of liver) compared with noncirrhotic livers (n = 6; median, 86 mL/minute/100 g; P = 0.002). Total blood flow into the native liver was negatively correlated with PELD (P < 0.001) and liver CPA (P = 0.005). Median portosystemic gradient was 14.5 mm Hg in children with cirrhosis and positively correlated with PELD (P < 0.001). Portal vein (PV) hypoplasia was observed mainly in children with BA (P = 0.02). Systemic hemodynamics were not altered in our children with cirrhosis. Twenty-one children met the intraoperative criteria for PV reconstruction using a portoplasty technique during the LT procedure and had a smaller PV diameter at pretransplant Doppler ultrasound (median = 3.4 mm; P < 0.001). Cirrhosis in children appears also as a hemodynamic disease of the liver, correlated with cirrhosis severity. Surgical technique for PV reconstruction during LT was adapted accordingly. Liver Transplantation 23 1440-1450 2017 AASLD.

Does Postoperative Cardiac Troponin-I Have Any Prognostic Value in Predicting Midterm Mortality After Congenital Cardiac Surgery?

OBJECTIVES: This study evaluated the prognostic value of postoperative cardiac troponin-I (cTnI) in predicting all-cause mortality up to 3 months after normothermic congenital cardiac surgery. DESIGN: Prospective observational study. SETTING: University hospital. PARTICIPANTS: All children ages 0 to 10 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: cTnI was measured after the induction of anesthesia but before the surgery, at the pediatric intensive care unit arrival, and at 4, 12, and 24 hours postoperatively. Follow-up was extended up to 6 months. Overall, 169 children were analyzed, of whom 165 were survivors and 4 were nonsurvivors. cTnI levels were significantly higher in nonsurvivors only at 24 hours (p = 0.047). Children undergoing surgery with cardiopulmonary bypass (CPB) had significantly higher cTnI concentrations compared with those without CPB (p<0.001). Logistic regression analysis was performed on the 146 children in the CPB group with the following predictive variables: CPB time, postoperative cTnI concentrations, the presence of a cyanotic malformation, and intramyocardial incision. None of the variables predicted mortality. Postoperative cTnI concentrations did not predict 6 months׳ mortality. Only cTnI at 24 hours predicted the length of stay in the pediatric intensive care unit. CONCLUSIONS: This study did not find that postoperative cTnI concentration predicted midterm mortality after normothermic congenital heart surgery. (ClinicalTrials.gov identifier: NCT01616394).

Long-Term Results of Balloon Valvuloplasty as Primary Treatment for Congenital Aortic Valve Stenosis: a 20-Year Review.

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 <1 year (infants), and 27 patients were older than 1 year (children). The invasive BAV peak-to-peak aortic valve gradient (mean 59 ± 22 mmHg) was immediately reduced (mean 24 ± 12 mmHg). The observed diminution of gradient was similar for each age group. Four patients had significant post-BAV AI. Mean follow-up after BAV was 11.4 ± 7 years. The last echo peak aortic gradient was 37 ± 18 mmHg and mean gradient was 23 ± 10 mmHg, and two patients had significant AI. Actuarial survival for the whole cohort was 88.2 and 72.9 % for the neonates. All infants, except one, and all children survived. Sixty-six percent of patients were free from surgery, and 58 % were free from any reintervention, with no difference according to age. Freedom from surgery after BAV at 5, 10, and 20 years, respectively, was 82, 72, and 66 %. Our study confirms that BAV as primary treatment for congenital AS is an efficient and low-risk procedure in infants and children. In neonates, the prognosis is more severe and clearly related to "borderline LV."

Long-term outcome and anaesthetic management for non-cardiac surgery after Fontan palliation: a single-centre retrospective analysis.

OBJECTIVES: The improved management of Fontan patients has resulted in good outcome. As such, these patients may necessitate care for non-cardiac surgery. We sought to determine the long-term outcome of our Fontan series palliated with the most recent surgical techniques. Our second objective was to report the incidence and the perioperative course after non-cardiac procedures. We reviewed the records of all patients with either a lateral tunnel or an extracardiac conduit Fontan between 1996 and 2008. Follow-up was recorded until June, 2013, including records regarding non-cardiac interventions. RESULTS: Overall, 58 patients were included. Of them, one patient underwent a takedown of his Fontan, and five patients died in the immediate postoperative course. The cumulative survival of the remaining 52 patients was 81%. There was no significant difference in survival between right and left ventricle morphologies (p=0.56), nor between both types of Fontan (p=0.9). Chronic arrhythmias (25%), fatigue/dyspnoea (40%), thrombotic complications (19%), and embolic events (10%) were among the most recurrent comorbidities. In total, 45 non-cardiac interventions were performed on 26 patients, with three bleeding complications and one death. CONCLUSIONS: This study shows excellent long-term survival after both lateral tunnel and extracardiac conduit Fontan. The incidence of cardiovascular morbidity remains high, however. We also report a high number of non-cardiac interventions. Thorough understanding of the Fontan physiology is mandatory when non-cardiac anaesthesiologists are in charge of these patients.

Transcatheter Sapien valve implantation in a native tricuspid valve after failed surgical repair.

OBJECTIVES: We describe the first report of a transcatheter Sapien implantation in a native tricuspid valve after multiple failed surgical repairs with a lack of prosthetic material and radiographic landmarks. METHODS AND RESULTS: A 47-year old female underwent multiple valve repairs and replacements including three tricuspid valve repairs without surgical ring or bioprosthesis implantation. She developed signs of right heart failure associated with a mixed tricuspid disease combining a severe stenosis and regurgitation. After surgical turn down, a revalvulation using a transcatheter approach was attempted. The challenges in this case were the absence of a stiff region to anchor the percutaneous valve, the lack of radiographic landmarks and the difficulties of precise annulus measurements. The applied strategy was -under general anesthesia and extracorporeal membrane oxygenation-: balloon sizing, prestenting of the tricuspid annulus using covered stents followed by Sapien valve implantation through the femoral vein under fluoroscopy and transoesophageal echocardiography (TEE). The procedure was successfull, solving the tricuspid leak and stenosis (peak gradient from 22 to 3 mm Hg) using two Sapien for a perfect positioning. It was complicated by pulmonary bleeding due to a distal wire exit, treated successfully by coil embolization. The clinical and echocardiographic outcome was good up to 5 months. CONCLUSIONS: Transcatheter Sapien valve implantation in a native tricuspid valve after failed multiple surgical repairs is feasible by the femoral vein. Technical challenges due to the lack of rigid landing zone and fluoroscopic markers were solved by prestenting and valve implantation under bi-plane fluoroscopic and TEE guidance.

Twin-to-twin transfusion syndrome: perinatal outcome and recipient heart disease according to treatment strategy.

AIM: The aims of the study were to compare perinatal outcome and assess recipient cardiac disease according to treatment strategy (amnioreduction (AR), laser or selective feticide). METHODS: We retrospectively reviewed 81 consecutive cases of twin-to-twin transfusion syndrome diagnosed before 28 weeks between 1993 and 2007. RESULTS: Although fetuses treated by laser were younger at diagnosis (median 20.4 vs. 22.4 weeks, P = 0.01), they were significantly older at birth (median 33.6 vs. 28.5 weeks, P = 0.004) than those treated by AR. Neonatal morbidity was globally lower after laser than AR, and cardiac insufficiency tended to be less frequent (31% vs. 57%, P = 0.09). There was a trend towards increased perinatal survival after laser treatment (68% vs. 49%, P = 0.1). Heart failure was the cause of death in half (23/46) of the recipients. Fetal heart failure leading to death was 2.7 times more frequent after AR than after laser (n = 11 vs. n = 4), and all four neonatal cardiac deaths occurred after AR. Compared with laser, selective feticide did not further improve the outcome. CONCLUSIONS: Heart failure was an important cause of perinatal morbidity and death. However, laser therapy resulted in a longer diagnosis-delivery interval and lower global neonatal morbidity than AR, with a trend towards increased perinatal survival. Improved outcome after laser treatment compared with AR might be related to its impact on recipient heart disease.

Catheter interventions in congenital heart disease without regular catheterization laboratory equipment: the chain of hope experience in Rwanda.

This report describes the feasibility and safety of cardiac catheterization in a developing country without access to a regular cardiac catheterization laboratory. The equipment used for imaging consisted of a monoplane conventional C-arm X-ray system and a portable ultrasound machine using the usual guidewires and catheters for cardiovascular access. In this study, 30 patients, including 17 children younger than 2 years and 2 adults, underwent catheterization of the following cardiac anomalies: patent ductus arteriosus (20 patients) and pulmonary valve stenosis (9 patients, including 2 patients with critical stenosis and 3 patients with a secundum atrial septal defect). Except for two cases requiring surgery, the patients were treated successfully without complications. They all were discharged from hospital, usually the day after cardiac catheterization, and showed significant clinical improvement in the follow-up evaluation. Cardiac catheterization can be performed safely and very effectively in a country with limited resources. If patients are well selected, this mode of treatment is possible without the support of a sophisticated catheterization laboratory.

Aortic Coarctation Stenting in Adolescents and Adults: A Single-Center Experience.

PURPOSE/BACKGROUND: The aim of this study was to evaluate the short and midterm results of aortic coarctation (AoCo) stenting in an adolescent and adult population. METHODS: All patients with a AoCo older than 14 years treated by stent placement between December 2000 and November 2016 were included in this study. Twenty-eight patients with an invasive peak systolic pressure gradient >20 mmHg were identified. Number of redilations, non-invasive systolic blood pressure, peak systolic pressure gradient, antihypertensive medication intake, claudication status and complications were evaluated. RESULTS: Twenty-two covered and 6 uncovered stents were successfully placed. Peak systolic pressure gradient decreased immediately after stenting from a mean of 32 mmHg to 0 mmHg (± 7 mmHg). Mean AoCo diameter increased from 8 tot 16 mm (± 4 mm). Peripheral arterial injury was seen in 2 patients (7.1%). The mean follow-up time was 60 ± 49 months. Redilation of the stent was required in 4 patients, 2 to accommodate for growth and 2 for restenosis. Six (35%) patients could stop all antihypertensive medication. All claudicants (6/28) became and remained asymptomatic after surgery and during their follow-up. No aneurysms, stent fractures or dissections were noticed. There were 2 stent migrations during the first procedure with only 1 needing additional stent placement. CONCLUSION: Aortic coarctation stenting is a safe and effective treatment that significantly reduces the peak systolic pressure gradient. Antihypertensive medication can be reduced, and increase of walking distance in claudicants can be obtained. Younger patients may need more frequent reinterventions to accommodate for growth.

Percutaneous transcatheter closure of interatrial septal defect in adults: procedural outcome and long-term results.

BACKGROUND: Percutaneous transcatheter closure of patent foramen ovale (PFO) and atrial septal defect (ASD) has been shown to be feasible. AIM: The aim of this study was to evaluate the safety and efficacy of transcatheter interatrial septal shunt closure with prosthesis implantation in adults patients during long-term follow-up. In addition, the impact of thrombophilia and pulmonary hypertension on the outcome were investigated. METHODS: Between June 1999 and November 2009, 287 patients (112 males, 43 ± 14 years) were treated in our institution by transcatheter closure of PFO (N = 175) or ASD (N = 112). Clinical and echocardiographic follow-up were prospectively performed at 1, 6 and 12 months followed by a 1 once a year evaluation. RESULTS: All procedures were successful with eight procedural complications (2.7%): one stroke, two femoral pseudoaneurysms, three transient atrial fibrillation, two minors pericardial effusions. Among patients with presumed paradoxical embolism, thrombophilia was observed in 29 patients (17%); only one of them experienced a recurrent stroke. Among patients with ASD, pulmonary hypertension was observed in 32 cases (28%) and significantly reduced 6 months after shunt closure (from 47 ± 7 to 31 ± 11 mm Hg, P < 0.0001). 99% of patients achieved a complete follow-up. Clinical improvement was observed in 93%. Freedom from death, cardiac surgery or recurrent embolism was 98 ± 1% at 5 years. CONCLUSION: Percutaneous transcatheter interatrial septal defect closure is a safe and effective treatment in adults patients, even in case of thrombophilia or pulmonary hypertension, during a long-term follow-up, up to 11 years.

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

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

The Pulmonary Autograft After the Ross Operation: Results of 25-Year Follow-Up in a Pediatric Cohort.

BACKGROUND: Progressive autograft dilation and need for later reoperation remain major concerns of the Ross procedure. The study investigates the clinical outcome after the Ross operation, including a longitudinal analysis of autograft dimensions over 25 years. METHODS: From November 1991 to April 2019, 137 patients underwent a Ross procedure at the University Hospitals of UCL (Université catholique de Louvain)-Brussels and Ghent. Inclusion criteria were less than or equal to 18 years of age and pulmonary autograft implantation by root replacement. Outcome focused on survival, reoperation rate, and autograft size evolution through linear mixed-model analysis. RESULTS: A Ross or Ross-Konno operation was performed in 110 (80%) and 27 (20%) patients at a median age of 10.4 (interquartile range [IQR], 4.7-14.3) years and 0.5 (IQR, 0.04-5.2) years, respectively. Overall 10-year and 20-year survival was 87% ± 3% and 85% ± 3%, respectively, but was 93% ± 3% for isolated Ross patients. Right ventricular outflow tract-conduit exchange was required in 20.3%, whereas autograft-related reoperation was performed in 14 (10.7%) patients at a median interval of 14 (IQR, 9-16) years, for aortic regurgitation (n = 2) and autograft dilation (n = 12). Autograft z-values increased significantly at the sinus and sinotubular junction (STJ) compared with the annulus (annulus = 0.05 ± 0.38/y, sinus = 0.14 ± 0.25/y, STJ = 0.17 ± 0.34/y; P = .015). The z-value slope for autograft dimensions was significantly steeper for Ross-Konno vs Ross patients (annulus: P = .029; sinus: P < .001; STJ: P = .012), and for children having aortic arch repair (annulus: P = .113, sinus: P = .038; STJ: P = .029). CONCLUSIONS: The Ross operation offers children requiring aortic valve replacement an excellent survival perspective, with an acceptable risk of autograft reoperation within the first 25 years. Contrary to the autograft annulus, dilation of the sinus and STJ size is of concern. Closer surveillance of autograft dimensions might be required in patients who underwent a Ross-Konno procedure or aortic arch reconstruction.

Development of renal and iliac aneurysms in a child with generalized infantile myofibromatosis.

Infantile myofibromatosis is a rare disorder characterized by the formation of tumors in the skin, soft tissues, bone, and viscera. We report the case of a 3-week-old girl who presented with severe hypertension due to generalized infantile myofibromatosis including renal involvement. The infant was treated by chemotherapy and showed progressive regression of the tumors. However, her evolution was marked by the development of aneurismal dilations of the renal and iliac arteries as observed in fibromuscular dysplasia. We discuss the possibility of a link between these two mesenchymal disorders.

Congenital heart disease in 111 225 births in Belgium: birth prevalence, treatment and survival in the 21st century.

AIM: To investigate the birth prevalence, treatment modalities and short-term survival of children with congenital heart disease who were born in 2002. METHODS: We undertook a retrospective review of medical records of all patients who were born in 2002, and were diagnosed, treated and/or followed-up in one of the seven-paediatric cardiology programmes in Belgium. RESULTS: In 111 225 births, 921 children with congenital heart disease were detected, yielding a birth prevalence of 8.3 per 1000. The most frequently occurring conditions were ventricular septal defects (VSDs) (33%), ostium secundum atrial septal defects (18%) and pulmonary valve abnormalities (10%). Thirty-nine percent of the children either had a cardiosurgical operation or catheter intervention. In this study, 4% of the children died. The actuarial survival at 6 months and 1 year of age was 97% and 96%, respectively and remained stable after then. Compared to other heart defects, mortality was higher in univentricular physiology, pulmonary atresia with VSD, left ventricle outflow obstruction and tetralogy of Fallot. CONCLUSION: Survival of congenital heart disease is excellent and continued to improve in the early 21st century. New therapeutic options are increasingly used. This study provides baseline data for the longitudinal follow-up of this cohort.

Outcome after percutaneous closure of a patent foramen ovale using the Intrasept device: a multi-centre study.

OBJECTIVES: This multi-centre study reports safety and efficacy of percutaneous patent foramen ovale (PFO) closure, using the fourth generation Intrasept device. BACKGROUND: PFO has been associated with paradoxical embolism and cryptogenic stroke. Percutaneous PFO closure seems to reduce the risk for recurrent paradoxical thrombo-embolism. Currently, different devices are used for PFO closure. METHODS: Patients, who underwent a PFO closure with the Intrasept device (Cardia, Eagan, MN) between July 2002 and September 2006, were included in the study. The primary endpoint was defined as reoccurrence of stroke, transient ischemic attack (TIA), or peripheral thrombo-embolism. Peri-procedural and mid-term complications were reported. RESULTS: Four-hundred thirty patients (mean age 50.7 +/- 13.0 years, 231 men) underwent closure. The indications were cryptogenic stroke (69.8%), TIA (23.5%), peripheral embolism (3.3%), and other (3.5%). The median follow-up time was 0.8 years, range 3.9 years. The primary endpoint occurred in 0.5% for stroke, in 2.5% for TIA, and in none for peripheral embolism. Peri-procedural complications were reported in 11.5% of cases, from which 0.2% was defined as major. No severe complications occurred during mid-term follow-up. A residual shunt was present in 12.5% of patients who did not suffer from a recurrent event, compared to 36.4% of patients who reached the primary endpoint (P = 0.04). CONCLUSION: This multi-centre study suggests that percutaneous closure of a symptomatic PFO with the fourth generation Intrasept device is safe and might be effective to prevent the recurrence of paradoxical thrombo-embolic events.

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

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

Aortic valve repair in the paediatric population: insights from a 38-year single-centre experience.

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.