Expert management of congenital portosystemic shunts and their complications.

Congenital portosystemic shunts are often associated with systemic complications, the most challenging of which are liver nodules, pulmonary hypertension, endocrine abnormalities, and neurocognitive dysfunction. In the present paper, we offer expert clinical guidance on the management of liver nodules, pulmonary hypertension, and endocrine abnormalities, and we make recommendations regarding shunt closure and follow-up.

Pediatric hepatic hemangiomas: spectrum and prognostic significance of initial ultrasound findings.

BACKGROUND: Hepatic hemangiomas may be associated with serious complications; however, it is unknown whether ultrasound (US) features can predict complications. OBJECTIVE: To analyze initial US features of hepatic hemangiomas predictive of complications. MATERIALS AND METHODS: This is a single-center retrospective cohort study of clinical, biological, and imaging data of infants with hepatic hemangioma between 2000 and 2018. Patients were categorized as having or not having any complication(s). Associations between initial US features and complications were analyzed through logistic regression. Receiver operating characteristic (ROC) curve analyses were performed to determine optimal cutoff values for continuous variables. Stepwise forward logistic regression was used to construct risk prediction models with training and validation sets. Model calibration and discrimination were evaluated using Hosmer-Lemeshow tests, area under the ROC curve, and overall accuracy. RESULTS: Of 112 infants with hepatic hemangioma, 67 (60%) had focal, 32 (28%) had multifocal, and 13 (12%) had diffuse lesions, with complication rates of 51%, 34%, and 92%, respectively, mostly cardiac (54/57, 95%). The US characteristics of the hemangiomas were diverse. Risk factors for complications included diffuse subtype; large tumor volume (focal forms); elevated peak systolic hepatic arterial velocity (PSV); and hepatic vein dilation. For focal forms, initial tumor volume >40 ml and PSV >100 cm/s had >70% sensitivity and specificity, respectively, to predict complications; a model including these variables had 75% overall accuracy in the validation set. For multifocal/diffuse forms, a PSV >115 cm/s had sensitivity and specificity to predict complications of >70%; a model including this variable had 78% overall accuracy in the validation set. CONCLUSION: Diffuse subtype, large tumor volume, elevated hepatic arterial PSV, and hepatic vein dilation are risk factors for complications of hepatic hemangiomas.

Cardiovascular events in perimembranous ventricular septal defect with left ventricular volume overload: a French prospective cohort study (FRANCISCO).

The long-term prospective multi-centre nationwide (French) observational study FRANCISCO will provide new information on perimembranous ventricular septal defect with left ventricular overload but no pulmonary hypertension in children older than 1 year. Outcomes will be compared according to treatment strategy (watchful waiting, surgical closure, or percutaneous closure) and anatomic features of the defect. The results are expected to provide additional guidance about the optimal treatment of this specific population, which is unclear at present. BACKGROUND: The management of paediatric isolated perimembranous ventricular septal defect (pmVSD) with left ventricle (LV) volume overload but no pulmonary arterial hypertension (PAH) remains controversial. Three therapeutic approaches are considered: watchful waiting, surgical closure, and percutaneous closure. We aim to investigate the long-term outcomes of these patients according to anatomic pmVSD characteristics and treatment strategy. METHODS: The Filiale de Cardiologie Pediatrique et Congénitale (FCPC) designed the FRANCISCO registry, a long-term prospective nationwide multi-centre observational cohort study sponsored by the French Society of Cardiology, which enrolled, over 2 years (2018­2020), patients older than 1 year who had isolated pmVSD with LV volume overload. Prevalent complications related to pmVSD at baseline were exclusion criteria. Clinical, echocardiographic, and functional data will be collected at inclusion then after 1, 5, and 10 years. A core lab will analyse all baseline echocardiographic data to depict anatomical pmVSD features. The primary outcome is the 5-year incidence of cardiovascular events (infective endocarditis, sub-aortic stenosis, aortic regurgitation, right ventricular outflow tract stenosis, tricuspid regurgitation, PAH, arrhythmia, stroke, haemolysis, heart failure, or death from a cardiovascular event). We plan to enrol 200 patients, given the 10% estimated 5-year incidence of cardiovascular events with a 95% confidence interval of ±5%. Associations linking anatomical pmVSD features and treatment strategy to the incidence of complications will be assessed. CONCLUSIONS: The FRANSCICO study will provide the long-term incidence of complications in patients older than 1 year with pmVSD and LV volume overload. The results are expected to improve guidance for treatment decisions.

Synergic PDE3 and PDE4 control intracellular cAMP and cardiac excitation-contraction coupling in a porcine model.

AIMS: Cyclic AMP phosphodiesterases (PDEs) are important modulators of the cardiac response to ß-adrenergic receptor (ß-AR) stimulation. PDE3 is classically considered as the major cardiac PDE in large mammals and human, while PDE4 is preponderant in rodents. However, it remains unclear whether PDE4 also plays a functional role in large mammals. Our purpose was to understand the role of PDE4 in cAMP hydrolysis and excitation-contraction coupling (ECC) in the pig heart, a relevant pre-clinical model. METHODS AND RESULTS: Real-time cAMP variations were measured in isolated adult pig right ventricular myocytes (APVMs) using a Förster resonance energy transfer (FRET) biosensor. ECC was investigated in APVMs loaded with Fura-2 and paced at 1 Hz allowing simultaneous measurement of intracellular Ca2+ and sarcomere shortening. The expression of the different PDE4 subfamilies was assessed by Western blot in pig right ventricles and APVMs. Similarly to PDE3 inhibition with cilostamide (Cil), PDE4 inhibition with Ro 20-1724 (Ro) increased cAMP levels and inotropy under basal conditions. PDE4 inhibition enhanced the effects of the non-selective ß-AR agonist isoprenaline (Iso) and the effects of Cil, and increased spontaneous diastolic Ca2+ waves (SCWs) in these conditions. PDE3A, PDE4A, PDE4B and PDE4D subfamilies are expressed in pig ventricles. In APVMs isolated from a porcine model of repaired tetralogy of Fallot which leads to right ventricular failure, PDE4 inhibition also exerts inotropic and pro-arrhythmic effects. CONCLUSIONS: Our results show that PDE4 controls ECC in APVMs and suggest that PDE4 inhibitors exert inotropic and pro-arrhythmic effects upon PDE3 inhibition or ß-AR stimulation in our pre-clinical model. Thus, PDE4 inhibitors should be used with caution in clinics as they may lead to arrhythmogenic events upon stress.

Transcatheter pulmonary valvuloplasty in neonates with pulmonary atresia and intact ventricular septum.

BACKGROUND: Transcatheter pulmonary valvuloplasty in neonates with pulmonary atresia and intact ventricular septum (PA-IVS) or duct-dependent pulmonary valve stenosis (DD-PVS) has become a reasonable alternative to surgical right ventricle decompression. AIM: To investigate mid-term outcomes following pulmonary valvuloplasty. METHODS: Sixty-five neonates with PA-IVS (n=29) or DD-PVS (n=36) (median age 4 days; mean weight 3.0kg) undergoing pulmonary valvuloplasty were reviewed retrospectively. Procedural data and clinical outcomes were assessed. RESULTS: Pulmonary valvuloplasty was successful in 59 patients (90.8%). Preterm birth, larger tricuspid valve annulus diameter and PA-IVS correlated with procedural failure. Eleven patients (18.6%) required a Blalock-Taussig shunt during early follow-up, despite valvuloplasty. These neonates had smaller tricuspid and pulmonary valve annulus Z-scores (-1.9 vs. -0.8 [p=0.04] and -2.5 vs. -0.9 [P=0.005], respectively) and a higher incidence of "bipartite" right ventricle (P=0.02). Mean follow-up was 5.4±3.3 years. Mortality after successful valvuloplasty was 8.5% (n=5). Among the 54 survivors, biventricular repair was achieved in 52 patients (96.3%), including nine with a previous Blalock-Taussig shunt. The cumulative rate of subsequent surgery (excluding Blalock-Taussig shunt) was 13.7% (95% confidence interval 6.8-26.7%) and 16.4% (95% confidence interval 8.5-30.4%) at 2 and 4 years, respectively. Secondary surgery was significantly more frequent in PA-IVS compared with DD-PVS, and in neonates with a Blalock-Taussig shunt (P=0.003 and 0.01, respectively). CONCLUSIONS: Selected neonates with DD-PVS or PA-IVS managed by transcatheter pulmonary valvuloplasty had a good mid-term outcome. In neonates with a borderline small right ventricle, a hybrid strategy with a supplementary source of pulmonary blood flow can be efficient to achieve biventricular repair.

Outcomes and prognostic factors for postsurgical pulmonary vein stenosis in the current era.

BACKGROUND: The optimal management and prognostic factors of postsurgical pulmonary vein stenosis remain controversial. We sought to determine current postsurgical pulmonary vein stenosis outcomes and prognostic factors in a multicentric study in the current era. METHODS: Seventy-five patients with postsurgical pulmonary vein stenosis who underwent 103 procedures in 14 European/North American centers (2000-2012) were included retrospectively. A specific pulmonary vein stenosis severity score was developed on the basis of the assessment of each pulmonary vein. End points were death, pulmonary vein reintervention, and restenosis. A univariate and multivariate risk analysis was performed. RESULTS: Some 76% of postsurgical pulmonary vein stenosis occurred after repair of a total anomalous pulmonary venous return. Sutureless repair was used in 42 of 103 procedures (41%), patch veinoplasty was used in 28 procedures (27%), and endarterectomy was used in 16 procedures (16%). Overall pulmonary vein restenosis, reintervention, and mortality occurred in 56% (n = 58/103), 49% (n = 50/103), and 27% (n = 20/75), respectively. Sutureless repair was associated with less restenosis (40% vs 67%; P = .007) and less reintervention (31% vs 61%; P = .003). Mortality after sutureless repair (20%; 7/35) tends to be lower than after nonsutureless repair (33%; 13/40) (P = .22). A high postoperative residual pulmonary vein stenosis score at the time of hospital discharge was an independent risk factor for restenosis (hazard ratio [HR], 1.55; P < 10-4), reintervention (HR, 1.33; P < 10-4), and mortality (HR, 1.37; P < 10-4). The sutureless technique was an independent protective factor against restenosis (HR, 0.27; P = .006). CONCLUSIONS: Postsurgical pulmonary vein stenosis still has a guarded prognosis in the current era. The sutureless technique is an independent protective factor against restenosis. The severity of the residual disease evaluated by a new severity score is an independent risk factor for poor outcomes regardless of surgical technique.

Neurocognitive and Psychological Outcomes in Adults With Dextro-Transposition of the Great Arteries Corrected by the Arterial Switch Operation.

BACKGROUND: Neurodevelopmental impairments have frequently been described in children and adolescents with dextro-transposition of the great arteries (d-TGA). The arterial switch operation (ASO) to correct d-TGA has been used for more than 30 years, and more than 90% of these patients now reach adulthood. However, very little is known about their long-term functional outcomes. The present study investigated neurocognitive outcomes and the prevalence of psychiatric disorders in adults with d-TGA corrected by ASO. METHODS: Neurocognitive functioning was comprehensively assessed (general intellectual functioning, language, attention, visual-spatial skills, executive functions, memory) in 67 adults (59.7% men) with d-TGA (aged 22.9 ± 3.4 years) and in 43 healthy individuals. The prevalence of psychiatric disorders, including depression and anxiety, was evaluated using a structured diagnostic interview. We also analyzed patient- and operative-related risk factors associated with outcomes. RESULTS: Compared with the general population and the control group, adults with d-TGA displayed reduced performance in tasks assessing attention, visual-spatial skills, executive functions, and memory (all p < 0.05). Compared with controls, patients had also a higher lifetime prevalence of depression (43% vs 19%, p = 0.008) and anxiety disorders (54% vs 33%, p = 0.025). Predictors of long-term outcomes included gender and parental socioeconomic and educational status (all p < 0.05). CONCLUSIONS: Adults who have undergone a neonatal ASO to correct d-TGA have an increased risk of cognitive deficits and psychiatric disorders. Evaluation of long-term neuropsychological and psychosocial outcomes in early adulthood is a crucial step to anticipate for adapted treatment strategies in adults with congenital heart disease.

Primary Pulmonary Vein Stenosis: Outcomes, Risk Factors, and Severity Score in a Multicentric Study.

BACKGROUND: Primary pulmonary vein stenosis (PPVS) still carries a poor prognosis, and prognostic factors remain controversial. The aim of this study was to determine outcomes and prognostic factors after PPVS repair in the current era. METHODS: Thirty patients with PPVS and a normal pulmonary vein (PV) connection operated on in 10 European/North American centers (2000-2012) were included retrospectively. A specific PVS severity score was developed based on the assessment of each PV. Studied end points were death, PV reoperation, and restenosis. A univariate and multivariate risk analysis was performed. RESULTS: The mean number of affected PVs per patient was 2.7 ± 1.1. Sutureless repair was used in 21 patients (70%), endovenectomy was used in 5 patients, and patch venoplasty was used in 4 patients. Overall PV restenosis, reoperation, and mortality occurred in 50%, 40%, and 30% of patients respectively. Freedom from mortality, reoperation, and restenosis at 8 years of follow-up was 70% ± 8%, 62% ± 8%, and 47% ± 9%, respectively. Restenosis and mortality rates after sutureless repair versus nonsutureless repair were 57% (n = 12 of 21) versus 33% (n = 3 of 9) (p = 0.42) for restenosis and 38% (n = 8 of 21) versus 11% (n = 1 of 9) (p = 0.21) for mortality. Patients selected for a sutureless technique were younger and smaller and had more severe disease before operation. A postoperative high PVS score and pulmonary hypertension 1 month after the operation were independent risk factors for restenosis (hazard ratio [HR], 1.34; p = 0.002 and HR, 6.81; p = 0.02, respectively), reoperation (HR, 1.24; p = 0.01 and HR, 7.60; p = 0.02), and mortality (HR, 1.39; p = 0.01 and HR, 39.5; p = 0.008). CONCLUSIONS: Primary PVS still has a guarded prognosis in the current era despite adoption of the sutureless technique. Postoperative pulmonary hypertension and severity of disease evaluated by a new severity score are independent prognostic factors regardless of surgical technique.

Cognitive outcomes and health-related quality of life in adults two decades after the arterial switch operation for transposition of the great arteries.

OBJECTIVE: The study objective was to evaluate the cognitive and psychosocial outcomes of young adults who underwent an arterial switch operation for transposition of the great arteries. METHODS: Sixty-seven adults with transposition of the great arteries (aged 22.9 ± 3.3 years) and 43 healthy subjects matched in age, gender, and educational level participated. Global cognitive functioning, psychologic state, and health-related quality of life were evaluated using validated tools. We analyzed patient-related and procedure-related risk factors associated with cognitive and psychosocial outcomes. RESULTS: Some 69% of patients had an intelligence quotient greater than 85 (normal range, 85-115). Mean full-scale, verbal, and performance intelligence quotients were lower in patients (94.9 ± 15.3, 96.8 ± 16.2, 93.7 ± 14.6, respectively) than in healthy subjects (103.4 ± 12.3, P = .003; 102.5 ± 11.5, P = .033; 103.8 ± 14.3, P < .001, respectively). Cognitive difficulties (intelligence quotient ≤-1 standard deviation) and impairments (intelligence quotient ≤-2 standard deviations) were more frequent in patients than in the general population (31% vs 16%, P = .001; 6% vs 2%, P = .030). Patients with cognitive difficulties had lower educational level (P < .001) and more grade retention at school (P = .007). Patients reported an overall satisfactory health-related quality of life; however, those with cognitive or psychologic difficulties reported poorer quality of life. Predictors of worse outcomes included lower parental socioeconomic and educational status, older age at surgery, and longer hospitalization stay. CONCLUSIONS: Despite satisfactory outcomes in most adults with transposition of the great arteries, a substantial proportion has cognitive or psychologic difficulties that may reduce their academic success and quality of life. Further studies are needed to better understand the long-term outcome of this population to provide prevention, surveillance, and care strategies.

Double-Outlet Right Ventricle With Noncommitted Ventricular Septal Defect and 2 Adequate Ventricles: Is Anatomical Repair Advantageous?

The management of double-outlet right ventricle associated with anatomically noncommitted ventricular septal defect constitutes a surgical challenge. The limits for, and the specific outcomes after anatomical vs univentricular repair still remain to be established. Between 1993 and 2011, 36 consecutive patients presenting with double-outlet right ventricle or noncommitted ventricular septal defect (21 inlet, 10 muscular, and 5 central perimembranous) and 2 adequately sized ventricles underwent surgical repair at 2 centers. Right ventricular outflow tract obstruction was present in 18 of 36 patients (50%). A total of 21 patients had undergone previous palliative procedures. Anatomical repair (group I) by means of intraventricular baffle construction was performed in 24 (associated right ventricular outflow tract reconstruction in 12 and arterial switch in 5) at a median age of 10.5 months. Ventricular septal defect was surgically enlarged in 12 (50%) patients. The remaining 12 patients underwent univentricular repair (group II). There were 4 hospital deaths (11%), all in group I (P = 0.30 vs group II). A total of 8 of 20 patients in group I survivors underwent 13 reoperations after a median delay of 24 months: subaortic stenosis was the main cause for reoperation in 6 of 8 patients. There was 1 late death in group I and 2 late deaths in group II. The median follow-up was 5.6 years (95% CI: 0.2-9.8). The 10- year actuarial survival rate and freedom from reoperation were 74.7 ± 5% and 58 ± 5% in group I and 71 ± 7% and 70 ± 7% in group II, respectively. At the last visit, all survivors were in New York Heart Association class I-II. Univariate analysis showed that atrioventricular septal defect and isolated mitral cleft were associated with death (P = 0.04) and need for reoperation (P = 0.038). In conclusion, anatomical repair, associated with substantial rates of mortality and need for reoperation, should be considered with caution. Associated atrioventricular septal defect and isolated mitral cleft were the only risk factors for mortality and reoperation.

Impact of anatomic characteristics and initial biventricular surgical strategy on outcomes in various forms of double-outlet right ventricle.

OBJECTIVES: Surgical management of various forms of double-outlet right ventricle uses a variety of approaches depending on the underlying anatomic form. In this study, we sought to determine the risk factors of mortality and reoperation in those with double-outlet right ventricle undergoing biventricular repair, according to anatomic characteristics and initial surgical strategy. METHODS: Between 1992 and 2013, 433 patients were included in the study. Double-outlet right ventricle was classified as double-outlet right ventricle with subaortic ventricular septal defect associated with subpulmonary obstruction in 33% of patients (n = 141), with subaortic ventricular septal defect without subpulmonary obstruction in 30% of patients (n = 130), with subpulmonary ventricular septal defect in 32% of patients (n = 139), and with noncommitted ventricular septal defect in 5% of patients (n = 23). Three types of repairs were performed: (1) intraventricular baffle repair, n = 149 (34%); (2) intraventricular baffle repair with right ventricular outflow tract reconstruction, n = 163 (38%); and (3) intraventricular baffle repair with arterial switch operation, n = 121 (28%). RESULTS: Thirty-day overall mortality was 7.4%. Early reoperation was needed in 6% of the cases. Early mortality was higher in the intraventricular baffle repair with arterial switch operation group (P = .01). Survival at 10 years was 86.2%, and freedom from reoperation at 10 years was 61.4%. At last follow-up (median, 5.7 years; 95% confidence interval, 4.5-6.6), mortality and reoperation rates were similar in the different surgical strategy groups. Late reoperation and late mortality were significantly higher in the double-outlet right ventricle with noncommitted ventricular septal defect group (P < .01). In multivariate analyses, risk factors for reoperation were concomitant surgical procedures (P = .03) and duration of cardiopulmonary bypass (P < .01). Risk factors for mortality were restrictive ventricular septal defect (P = .01), mitral cleft (P < .01), and associated coronary artery anomalies (P = .01). CONCLUSIONS: Those with the anatomic type of double-outlet right ventricle with noncommitted ventricular septal defect were at higher risk for reoperation and mortality. Intraventricular baffle repair with arterial switch operation was the surgical strategy in patients at higher risk of early death. Initial surgical strategy did not influence the late outcomes.

Long-term outcomes of the arterial switch operation for transposition of the great arteries and ventricular septal defect and/or aortic arch obstruction.

OBJECTIVES: Long-term outcomes after the arterial switch operation (ASO) for complex transposition of the great arteries (TGA) should be clarified. METHODS: A retrospective study was conducted in patients operated on between 1982 and 1998. Overall 220 postoperative survivors, 79.1% with a ventricular septal defect, 13.2% with multiple ventricular septal defects, and 29.1% with aortic arch obstruction, were followed for 17 years (0-28 years). RESULTS: The conditional survival rate was 96.7% [95% confidence interval (CI): 94.4-99.1] at 25 years. Late sudden death occurred in 2 asymptomatic patients. The cumulative incidence rate of death or reinterventions was 3.8% (95% CI: 2.9-4.8) at 25 years, with age at ASO <10 days and aortic regurgitation at discharge identified as independent risk factors. The cumulative incidence rate of neoaortic regurgitation was 41.6% (95% CI: 20.5-62.8) at 25 years with an aorto-pulmonary diameter mismatch at the time of the ASO, age at ASO <10 days and aortic regurgitation at discharge identified as independent risk factors. At the last follow-up, 53 patients (24.1%) had neoaortic root dilatation with an aortic sinus z-score ≥3 and 6 of them had a Bentall operation at a median delay of 14.1 years since the ASO. The only independent factors for neoaortic root dilatation were male sex and an aorto-pulmonary diameter mismatch at the time of the ASO. CONCLUSIONS: Despite a continual rate of reinterventions, long-term survival and cardiovascular outcome are excellent after ASO for complex TGA. Dilatation of the neoaortic root and neoaortic regurgitation may be observed with time and 2 late sudden deaths occurred, justifying a close follow-up in all patients.

Concise Review: Pluripotent Stem Cell-Derived Cardiac Cells, A Promising Cell Source for Therapy of Heart Failure: Where Do We Stand?

Heart failure is still a major cause of hospitalization and mortality in developed countries. Many clinical trials have tested the use of multipotent stem cells as a cardiac regenerative medicine. The benefit for the patients of this therapeutic intervention has remained limited. Herein, we review the pluripotent stem cells as a cell source for cardiac regeneration. We more specifically address the various challenges of this cell therapy approach. We question the cell delivery systems, the immune tolerance of allogenic cells, the potential proarrhythmic effects, various drug mediated interventions to facilitate cell grafting and, finally, we describe the pathological conditions that may benefit from such an innovative approach. As members of a transatlantic consortium of excellence of basic science researchers and clinicians, we propose some guidelines to be applied to cell types and modes of delivery in order to translate pluripotent stem cell cardiac derivatives into safe and effective clinical trials.

Critical Congenital Heart Diseases in Preterm Neonates: Is Early Cardiac Surgery Quite Reasonable?

Prematurity is a recognized risk factor for morbidity and mortality following cardiac surgery. Postoperative and long-term outcomes after cardiac surgery performed in the preterm period are poorly described. The aim of this study was to analyze a population of preterm neonates operated on for critical congenital heart disease (CHD) before 37 weeks of gestational age (wGA) with special attention given to early and late mortality and morbidity. Between 2000 and 2013, 28 preterm neonates (median gestational age (GA) 34.3 weeks) underwent cardiopulmonary bypass (CPB) surgery for critical CHD before 37 wGA; records were retrospectively reviewed. All patients except three with single ventricle physiology had a single-stage anatomic repair. Overall mortality was 43 % (95 % CI 25-62). Risk factors for death were birth weight (p = 0.032) and weight at surgery (p = 0.037), independently of GA, preoperative status, CPB and aortic clamp time. Seven patients, including those with univentricular hearts, died during the postoperative period, and five in the first year after surgery. Median follow-up was 5.9 years (range 1 month-12.8 years). Kaplan-Meier survival rate was 75 % (95 % CI 59-91) at 1 month, and 57 % (95 % CI 39-75) at 1 and 5 years. Eight patients required reoperations after a delay of 2.8 ± 1.3 months; eight had bronchopulmonary dysplasia. At the end of follow-up, nine patients were asymptomatic. One-stage biventricular repair for critical CHD on preterm neonates was feasible. Mortality remained high but acceptable, mainly confined to the first postoperative year and related to small weight. Despite reoperations, long-term clinical status was good in most survivors. Further long-term prospective investigations are necessary to evaluate neurodevelopmental outcomes.

Portopulmonary Hypertension in Liver Disease Presenting in Childhood.

OBJECTIVE: Portopulmonary hypertension (POPH) is a known complication of cirrhosis in adults, but there is little information on its incidence and outcome in children with liver disease. We report 14 patients with POPH and present a synthesis of the medical literature. METHODS: Diagnosis of POPH in the 14 patients was based on right-sided heart catheterization displaying mean pulmonary artery pressure (mPAP) >25 mmHg, indexed pulmonary vascular resistances >3 Wood units · m, and pulmonary wedge pressure <15 mmHg. A literature review added 84 patients. RESULTS: In our unit, POPH was found in 0.5% of the children with portal hypertension, 0.9% of the children with end-stage liver disease awaiting transplantation, and 3 children with congenital portosystemic shunts (CPSSs). Analysis of 98 reported patients, including the 14 presented here, showed the cause of liver disease to be chronic liver disease or portal cavernoma in 76 instances (34 with a history of surgical portosystemic shunt) and CPSS in 22 instances. There was a precession with proven hypoxemia caused by hepatopulmonary syndrome in 6 patients. Median survival was 3 months in 56 untreated patients. An 80% 5-year probability of survival in 42 patients was treated by CPSS closure, pulmonary vasodilators, and/or liver transplantation. Mean pretransplant mPAP was 34 and 49 mmHg in transplant survivors and nonsurvivors, respectively. CONCLUSIONS: POPH is a rare but extremely severe complication of childhood liver disease. Portosystemic shunts, whether congenital or acquired, likely play an important causative role. Early diagnosis is crucial and requires systematic screening by echocardiography in children at risk.

Atrio-ventricular valve regurgitation in univentricular hearts: outcomes after repair†.

OBJECTIVES: The aim was to describe the early and mid-term outcome after atrio-ventricular valve (AVV) repair in patients with univentricular hearts (UVHs) and to identify risk factors for AVV reoperation and death. METHODS: This study is a retrospective review of patients undergoing valve repair for AVV regurgitation at any stage of univentricular palliation from 1998 to 2014. Patient- and procedure-related variables were analysed. RESULTS: A total of 31 consecutive patients underwent 38 procedures for ≥ moderate AVV regurgitation at a median age of 3.6 years. Thirty-two percent of patients had a common AVV, 26% had two AVVs, 22% had a dominant tricuspid valve and 19% had a dominant mitral valve. All patients underwent valve repair as a first procedure without early mortality. At discharge, patients preserved their ventricular function (fractional shortening <30%: preoperative 16% vs postoperative 22.5%, NS). In 19% (n = 6) of patients, the procedure was considered as failed because of significant residual regurgitation. There were three late deaths [median delay: 1 year (range 0.7-13.6)] and three heart transplantations. Six patients underwent seven AVV reoperations [median delay: 2 years (range 0.2-7.6)]. Longer intensive care stay (P = 0.022), longer total postoperative hospital stay (P = 0.039), higher total number of surgeries (P = 0.039), lower body mass index (P = 0.042) and higher preoperative mean pulmonary pressure (P = 0.047) were univariate risk factors for death/transplantation. Failed first AVV repair (P = 0.01), higher total number of surgeries (P = 0.026), lower body mass index (P = 0.031), male gender (P = 0.031) and need for valve repair before bidirectional cavopulmonary connection (P = 0.036) were univariate risk factors for AVV reoperation. In multivariate analysis, no univariate risk factor reached statistical significance. Freedom from death/transplantation was 84% (CI 95%: 70%-98%) at 5 and 10 years. Survival free from AVV reoperation was 72% (CI 95%: 52%-92%) at 5 years and 62% at 10 years (CI 95%: 36%-88%). Mean follow-up of survivors was 4.7 years (SD ± 4.3; range 0.2-15.6). At last visit, 96% of survivors were in NYHA Class I-II. Ninety-two percent had a ≤ mild residual regurgitation. CONCLUSIONS: In patients with a UVH and ≥ moderate AVV regurgitation, AVV repair is feasible without postoperative deterioration of their ventricular function. Nevertheless, these patients remain at increased risk for death/transplantation and AVV reoperation.

Right ventricular failure secondary to chronic overload in congenital heart diseases: benefits of cell therapy using human embryonic stem cell-derived cardiac progenitors.

OBJECTIVE: Despite the increasing incidence of right ventricular (RV) failure in adult patients with congenital heart disease, current therapeutic options are still limited. By contrast to left-heart diseases, cell-based myocardial regeneration applied to the right ventricle is poorly studied, even though it may be a therapeutic solution. As human embryonic stem cell-derived cardiac progenitors seem to be good candidates owing to their proliferation capacity, our aim was to assess, in a large animal model of overloaded RV dysfunction, the feasibility and effects of such a cell therapy. METHODS: Human MesP1(+)/SSEA-1(+) cardiogenic mesodermal cells were administered using multiple intramyocardial injections 4 months after a surgical procedure mimicking the repaired tetralogy of Fallot, and their effects were observed 3 months later on hemodynamic, rhythmic, and histologic parameters. RESULTS: All pigs (sham n = 6, treated n = 6) survived without complication, and cell therapy was clinically well tolerated. Although functional, contractility, and energetics parameters evolved similarly in both groups, benefits regarding arrhythmic susceptibility were observed in the treated group, associated with a significant decrease of peri-myocyte fibrosis (5.71% ± 2.49% vs 12.12% ± 1.85%; P < .01) without interstitial fibrosis change (5.18% ± 0.81% vs 5.49% ± 1.01%). Such a decrease could be related to paracrine effects, as no human cells could be detected within the myocardium. CONCLUSIONS: Cell therapy using intramyocardial injections of human MesP1(+)/SSEA-1(+) cardiogenic mesodermal cells seems to have benefits regarding overloaded RV tissue remodeling and arrhythmic susceptibility, but this mode of administration is not sufficient to obtain a significant improvement in RV function.

Late outcomes after arterial switch operation for Taussig-Bing anomaly.

OBJECTIVE: To assess the long-term results of the arterial switch operation (ASO) for Taussig-Bing Anomaly (TBA) and identify risk factors affecting outcomes. METHODS: Retrospective review and late follow-up was performed for all TBA patients from 1997 to 2010 (follow-up >3 years). Selection criteria included the absence of mitro-pulmonary continuity. RESULTS: Sixty-nine children underwent ASO at a median age of 24 days (interquartile range [IR] 11-125), with concomitant repair of aortic arch obstruction in 26 (37.7%). Complex coronary anatomy (n = 38; 55.0%) was common. Nine (13.0%) patients had staged repair. Hospital mortality was 5.8% (95% confidence interval [CI], 1.6%-14.2%; n = 4). Median follow-up was 11.2 years (IR 7.2-13.8). Subsequent mortality was confined to the first postoperative year (n = 5, 86% [95% CI, 78%-95%]), 1-, and 10-year survival). Overall mortality was related to coronary pattern (Yacoub types C and E vs A and D, multivariate, hazard ratio [HR] 12.2 [95% CI, 1.2-122.1], P = .03). At latest follow-up, 96% of the survivors are asymptomatic, with normal ventricular function. Cumulative incidence of reintervention at 10 years was 53% (95% CI, 28%-77%). Concomitant aortic arch obstruction was a predictor of reintervention (multivariate, HR 2.9 [95% CI, 1.1-7.4], P = .03). No mortality occurred upon reinterventions. CONCLUSIONS: In the largest series to date of ASO for TBA, mortality is confined to the first postoperative year, and related to coronary artery pattern. Beyond the first year, needed reinterventions are frequent, but with sustained functional status and no mortality over >10 years follow-up. Aortic arch obstruction is the main predictor for reintervention. Despite a significant rate of early events, favorable long-term outcomes argue for use of the ASO in TBA patients.

Closure of tubular patent ductus arteriosus with the Amplatzer Vascular Plug IV: feasibility and safety.

BACKGROUND: Closure of tubular patent ductus arteriosus remains a challenging procedure. Anecdotal use of Amplatzer Vascular Plug IV for tubular ductus closure has been reported but feasibility and safety in a consecutive patients' series remain unknown. METHODS: We performed a monocenter prospective study at the Marie Lannelongue Hospital in Paris, France. From 2009 to 2014, a total of 47 patients (39 infants, 3 children, and 5 adults) underwent ductus closure with the Plug IV. RESULTS: Ductus morphology was a type E in 34 (72.3%) patients and a type C in 13 (27.7%) patients. Ductus closure occurred in 39 (83.0%) infants at a median age of seven months (range: 3-23 months) and a median weight of 6.9 kg (range: 4.1-17.0 kg). A past history of prematurity and very low birth weight was found in 33 (70.2%) of them. Twelve (25.5%) patients had pulmonary hypertension. Mean Plug IV diameter was 1.9 ± 0.1 mm larger than the mean maximal ductus diameter. Early complete closure of the ductus was obtained in all patients. Early migration of an undersized Plug IV occurred in one (2.1%) patient and was suitable for percutaneous device retrieval. After a mean follow-up of 3.4 ± 1.4 years, all patients are alive and asymptomatic, no late complication occurred. CONCLUSION: Transcatheter closure of tubular ductus with the Amplatzer Vascular Plug IV can be safe and effective, with a 100% early occlusion rate. This device, suitable for a 4F sheath, is a new alternative for tubular ductus closure in low-body-weight infants.

Aortopulmonary window and the interrupted aortic arch: midterm results with use of the single-patch technique.

BACKGROUND: An aortopulmonary window (APW) associated with an interrupted aortic arch (IAA) can be associated with significant rates of perioperative mortality and recurrent arch obstruction. We assessed the outcomes associated with the use of a single pericardial patch technique for primary repair. METHODS: Between 2002 and 2011, 9 neonates and 2 infants with APW and IAA underwent single-stage repair, under a hypothermic (28°C) continuous cardiopulmonary bypass with antegrade selective cerebral perfusion. A single autologous pericardial patch (glutaraldehyde-fixed) was used both to augment the IAA end-to-side anastomosis and to close the APW by use of the "sandwich" technique. RESULTS: The IAA was type A in 6 patients and type B in 5 patients. The APW morphology was type I in 6 patients, type II in 4 patients, and type III in 1 patient. The median age and weight at operation were 11 days (range, 6 to 180 days) and 2.6 kg (range, 2.2 to 6.5 kg), respectively. The mean cardiopulmonary bypass and aortic cross-clamp times were 108.6 ± 27.5 minutes and 49.3 ± 13.4 minutes, respectively. One patient required additional closure of a ventricular septal defect. Delayed sternal closure was performed in 8 patients. The mean follow-up time was 6 ± 3 years. There were no early and no late deaths. Postoperative morbidity consisted of one postoperative stroke with no late sequelae. There were no reoperations. The last follow-up visits confirmed the absence of recurrent aortic arch obstruction and pulmonary artery branch stenosis in all patients. CONCLUSIONS: Primary anatomic repair of APW associated with IAA can be safely performed. The efficiency of the single-patch technique was confirmed by the restoration of normal functional anatomy of the great arteries and aortic arch during follow-up.