BACKGROUND:Shprintzen-Goldberg syndrome (SGS) shares skeletal features with Marfan syndrome (MFS), but differs in its craniofacial and neurodevelopmental features. Cardiovascular features have been specifically investigated in few of the 57 known patients with SGS described in the literature, making it difficult to determine their prevalence and characteristics. METHODS:We reviewed the medical records of an international cohort of 29 patients, with a particular focus on cardiovascular features. Data were compared with those of MFS. RESULTS:The sex ratio was 1.9 and median age was 23 years (range: 4-54). 13 patients (44.8%) had mitral regurgitation (MR), 11 (37.9%) had a thoracic aortic aneurysm (TAA) and 9 (31.1%) had aortic regurgitation (AR). No cases of aortic dissection were reported. None had beta-blockers as a primary prevention of aortic events. The Kaplan-Meier method revealed a 30 years risk of 47%, 33% and 22% for occurrence of MR, TAA and AR, respectively. A statistically significant association was found between variants in the Dachshund Homology Domain and the risk of aortic aneurysm (11/20 vs 0/9, p=0.036). CONCLUSION:Patients with SGS also significantly have cardiovascular manifestations, encouraging the implementation of a follow-up and preventive cardiovascular treatment identical to that of MFS.

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.BACKGROUNDThe 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.METHODSThe 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 (2018–2020), 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.CONCLUSIONSThe 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.

Congenital heart disease (CHD) can lead to under vascularization of placenta, which can affect fetal development and subsequent neurological outcome. No data are currently available regarding neurodevelopmental outcome of children born to mothers with CHD. Characteristics of pregnancy, birth and neonatal period, items of neurodevelopment during infancy recorded in health book, need for speech therapist, physiotherapist, school helper and grade repetition were retrospectively collected in children under 10 years old born to CHD mothers followed up in 5 French congenital heart disease centres, and compared to a control population (children and brotherhood from mother consulting in 2 paediatric traumatology emergency rooms). Children under 7 years old of both groups were prospectively screened for neurodevelopmental trouble using the neurodevelopmental test developed by the “Haute Autorité de Santé” (HAS). One hundred and nineteen children from 83 CHD mothers and 122 children from 118 control mothers were included. Children from CHD mothers were born earlier (37.9 ± 2.6 vs. 39.3 ± 1.5 WA) and with a higher rate of prematurity (17.6 vs. 4.9%). They displayed lower birth weights (2910 ± 650 vs. 3370 ± 500 g), lower APGAR scores at 1 minute (8.6 ± 2.3 vs. 9.3 ± 1.5) and a smaller head circumference at 9 months (44.7 ± 1.4 vs. 45.3 ± 1.4 cm). There was no difference in the age of walking and head circumference at 24 months, as well as grade repetitions and need for speech therapist, physiotherapist, or school helper. The HAS neurodevelopmental test suspected trouble in 5.9% of children from CHD mothers and 11.5% of control children (NS). Despite increased prematurity and worse APGAR score, children from mothers with CHD appear not to show symptoms of neurodevelopment impairment in our study.

Aims Ventricular tachycardia (VT) ablation has been proven to be effective and safe to avoid arrhythmia recurrences in patients with repaired congenital heart disease (CHD). However, some of these patients may present right ventricular (RV) access issues [agenesia or thrombosis of inferior vena cava (IVC)], making impossible to access the right ventricle through an inferior approach. In such patients, only a superior approach would theoretically be feasible. Methods and results All VT ablations performed through a jugular or subclavian approach in CHD patients between 2012 and 2017 were included. Among 247 patients scheduled for VT ablation, two patients underwent three VT ablation procedures via a superior approach for due to the inability to access the right ventricle through a conventional IVC access (IVC interruption with azygos continuation in one patient and IVC thrombosis in the other). Ablation was performed using a three-dimensional system through a superior approach, using a subclavian access in both cases. A redo ablation had to be performed in the first patient using a jugular approach. Large curve catheters were used to facilitate RV outflow tract access. Supposed critical isthmuses could be localized and ablated. Patients remained free from arrhythmias during follow-up. Conclusion In patients with repaired CHD and 'no femoral access', ablation of RV tachycardia can be performed using a subclavian or a jugular approach. Mapping may be challenging, requiring large curve catheters. Conventional isthmuses can be mapped and ablated successfully, and such patients should not be denied radiofrequency ablation.

Maternal cyanotic congenital heart disease (CHD) is considered a great maternal and fetal risks during pregnancy, but information on management of these pregnancies are lacking. The purpose of this study was to assess maternal and fetal outcome in patients with cyanotic CHD in a large cohort of patients. This multicenter retrospective study included pregnant women with cyanotic CHD followed in 11 French specialized centers from 1997 to 2015. Patients with pulmonary hypertension were excluded. We recorded maternal, obstetrical and neonatal outcome. Thirty-one patients (mean age 27 ± 6 years) had 71 pregnancies. There were 17 (26%) miscarriages and 48 (73%) complete pregnancies (≥ 20 week gestation (WG)). All pregnancies were singleton. Severe cardiac events occurred in 7 patients (23%, 95% CI [10–41]) and 6 complete pregnancies (8%, 95% CI [3–17]). Heart failure (n = 3) and arrhythmia (n = 2) were the main cardiovascular complications. There was no maternal death. No thromboembolism event occurred, and one patient experienced an infective endocarditis during postpartum. Obstetrical complications included mainly hemorrhages (n = 9, 13% of pregnancies). Small for gestational age (SGA) was diagnosed in 28%. The mean birth weight was 1897 ± 607 g at a mean gestational age of 33 ± 3WG, and 85% of newborns were premature. These two comorbidities were associated with an 11% neonatal mortality. Pre-pregnancy maternal oxygen saturation ≤ 85% was related to miscarriages and SGA (P ≤ 0.04). Women with cyanotic CHD can go through pregnancy with a low risk for themselves. However, cyanotic CHD is associated with a high incidence of fetal and neonatal complications.

Background. - The relationship between pulmonary arterial hypertension-specific drug therapy (PAH-SDT) and mortality in Eisenmenger syndrome (ES) is controversial.Aims. - To investigate outcomes in patients with ES, and their relationship with PAH-SDT.Methods. - Retrospective, observational, nationwide, multicentre cohort study.Results. - We included 340 patients with ES: genetic syndrome (n =119; 35.3%); pretricuspid defect (n=75; 22.1%). Overall, 276 (81.2%) patients received PAH-SDT: monotherapy (endothelin receptor antagonist [ERA] or phosphodiesterase 5 inhibitor [PDE51]) 46.7%; dual therapy (ERA + PDE51) 40.9%; triple therapy (ERA+PDE51+prostanoid) 9.1%. Median PAH-SDT duration was 5.5 years [3.0-9.1 years]. Events (death, lung or heart-lung transplantation) occurred in 95 (27.9%) patients at a median age of 40.5 years [29.4-47.6]. The cumulative occurrence of events was 16.7% [95% confidence interval 12.8-21.6%] and 46.4% [95% confidence interval 38.2-55.4%] at age 40 and 60 years, respectively. With age at evaluation or time since PAH diagnosis as time, scales, cumulative occurrence of events was lower in patients taking one or two PAH-SDTs (P=0.0001 and P=0.004, respectively), with the largest differences in the post-tricuspid defect subgroup (P< 0.001 and P< 0.02, respectively) versus patients without PAH-SDT. By multivariable Cox analysis, with time since PAH diagnosis as time scale, New York Heart Association/World Health Organization functional class III/IV, lower peripheral arterial oxygen saturation and pretricuspid defect were associated with a higher risk of events (P=0.002, P=0.01 and P=0.04, respectively), and one or two PAH-SDTs with a lower risk of events (P=0.009).Conclusions. - Outcomes are poor in ES, but seem better with PAH-SDT. ES with pretricuspid defects has worse outcomes despite the delayed disease onset. (C) 2017 Elsevier Masson SAS. All rights reserved.

Survival into adulthood of patients with unrepaired cyanotic congenital heart defects (CHDs) is possible when cyanotic CHDs are deemed unsuitable for radical surgical repair but are compatible with survival. These situations include, for example, complex pulmonary atresia with aortopulmonary collaterals and single-ventricle hearts (with and without earlier palliation). This is also the case when patients with cyanotic CHDs reach adulthood without serious symptoms requiring surgery, such as those with mild tetralogy of Fallot, Ebstein’s anomaly, and some cases of corrected transposition of the great arteries with pulmonary stenosis and ventricular septal defect. Many women with these heart conditions wish to become pregnant, which creates a situation of high maternal and fetal risks of complications.1 Management of these patients before, during, and after pregnancy has improved, with an earlier recognition of the underlying disease, improved understanding of cardiopulmonary physiopathology, better prenatal and peri-partum obstetric/anesthetic management, and the introduction of a multidisciplinary approach.2We retrospectively reviewed the charts of all pregnant women with cyanotic CHDs (n=51) who were followed in 11 adult CHD referral …

OBJECTIVE:There is growing evidence that maternal mortality in pregnant women with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) is lower than that in available data. In order to evaluate this hypothesis, we collected data of pregnancies in women with PAH-CHD.METHODS:Women with PAH-CHD followed in seven French referral centres were retrospectively included from 1997 to 2015. All pregnancies were recorded. We collected data on maternal, obstetrical and neonatal outcomes.RESULTS:28 pregnancies in 20 women (26±6 years old) with PAH-CHD were managed during this period. There were 18 complete pregnancies (≥20 weeks' gestation (WG)), 8 abortions and 2 miscarriages. Six (33%, 95% CI (11.9 to 54.3)) patients experienced severe cardiac events. The concerned women had lower resting oxygen saturation (79.6±4.1% vs 89.3±3.8%, p<0.01). The most common cardiac complications during the complete pregnancies were heart failure (n=4) and severe hypoxaemia (n=5). Heart failure was overall severe, requiring inotropic treatment in three patients, mechanical circulatory support in one and led to one maternal death (mortality=5.0% 95% CI (0.1 to 24.9)). Obstetrical complications occurred in 25% of pregnancies. Small for gestational age was diagnosed in 39% (7/18) of fetuses. 12/18 (67%) pregnancies were delivered by caesarean section, of which 10 in emergency for obstetrical reason. Prematurity was frequent (78%), but no neonatal death occurred.CONCLUSIONS:Outcome of pregnancy in women with PAH-CHD is better than previously reported, with only 5% maternal mortality in our cohort. However, because of the severity of heart failure and the high rate of neonatal complications, patients should still be advised against pregnancy.

Background: The aim of this study was to assess health-related quality of life in patients with pulmonary arterial hypertension associated with CHD and correlations with clinical status.Methods: This prospective cross-sectional observational study included CHD patients with pulmonary arterial hypertension in 14 tertiary-care centres in France. We used two health-related quality of life questionnaires - SF-36 and Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) - and one anxiety/depression Hospital Anxiety and Depression Scale (HADS) questionnaire.Results: Clinical data were collected for the 208 included patients (mean age: 42.6 years, range from 15.1 to 85.8 years, 69.7% female). Most patients were in NYHA functional class II (48.1%) and III (37.5%). Patients' phenotype was classified as Eisenmenger syndrome (70.7%), pulmonary arterial hypertension associated with systemic-to-pulmonary shunts (12.0%), with small defects (3.4%), or after corrective cardiac surgery (13.9%). In total, 76.4% of the patients were receiving pulmonary arterial hypertension-specific treatments. SF-36 scores showed impairment compared with normalised data. Health-related quality of life scores were significantly lower in females than in males for most dimensions of both questionnaires and were independent of the patients' phenotype, even after gender adjustment - except for CAMPHOR functioning - but significantly depended on NYHA functional class. The Hospital Anxiety and Depression Scale (HADS) scores suggested anxiety and depression associated with increasing NYHA functional class but independent of patients' phenotype. NYHA functional class, 6-minute walk distance, HADS, gender, and recent stressful event significantly affected quality of life in the multivariate analysis.Conclusions: This study showed impairment of quality of life in a large cohort of patients with pulmonary arterial hypertension associated with CHD with both generic and specific questionnaires. NYHA functional class and HADS scores were predictive of most quality of life scores.

BACKGROUND: There is emerging evidence showing that maternal mortality in pregnant women with pulmonary artery hypertension, such as Eisenmenger syndrome (ES), is lower in recent years than historically described. In order to analyze recent outcomes, we retrospectively collected data of pregnancies in women with ES from 1997 to 2015. METHODS: This multicenter study included women with ES, followed in 7 French referral centers for congenital heart disease. All pregnancies were included, including ectopic pregnancies, miscarriages and abortions. We collected data on maternal, obstetrical and neonatal outcome. RESULTS: Twenty nine pregnancies in 18 women (25 ± 6 years old) with ES were managed during this period. There were 21 complete pregnancies (≥20 week gestation (WG)), 7 abortions, and 1 miscarriage. Six (32%) patients experienced severe cardiac events. These patients had lower saturation (79% vs. 89%) and were older. The most common cardiac complications after 20WG were heart failure (n = 4) and deep desaturation (n = 3).These heart failures were severe, requiring inotropic treatment (n = 3) or ventricular assistance device (n = 1), and lead to the only maternal death (mortality = 5%). Obstetrical complications occurred in 38% of pregnancies. Small gestational for age was diagnosed in 33% (7/21) and was statistically related to basal saturation level of the patient (p = 0.03), and to the maternal body mass index (p = 0.04). 12/21 (57%) pregnancies were delivered by cesarean section, with 7/12 for cardiac indications. The mean birth weight was 1824 ± 594 g at a mean gestational age of 34 ± 3WG. There was a high incidence of prematurity (57%), and no fetal or neonatal death. CONCLUSIONS: Outcome of pregnancy in women with ES has improved with modern cardiologic and obstetrical management with a lower rate of maternal mortality. However, the severity of heart failure and the high rate of prematurity and SGA should still lead to counsel patients against pregnancy.

Background: Many cyanotic congenital heart diseases (CHD) are deemed unsuitable for radical repair but are compatible with survival. Previous studies suggest that cyanotic CHD are of great maternal and fetal risk to pregnancy, but information on management of these pregnant women is lacking. The purpose of this study was to determine maternal and fetal outcomes in patients with cyanotic CHD. Methods: This multicenter retrospective study included pregnant women with cyanotic CHD followed in 10 French specialized centers from 1992-2015. Patients with pulmonary hypertension were excluded. All pregnancies were reviewed. We observed maternal, obstetrical and neonatal outcomes. Results: Twenty four patients (27 ± 6 years old) had 55 pregnancies. There were 10 miscarriages (19%), 40 complete pregnancies (≥20 week gestation (WG)), 4 abortions and 1 ectopic pregnancy. All pregnancies were singleton. Severe cardiac events occurred in 6 (11%) pregnancies. There was no maternal death. Cardiac complications were arrhythmia (n = 3), heart failure (n = 3) and stroke attack (n = 1). Six patients experienced deep hypoxia during the peri-partum period. No infectious endocarditis occurred. Half of cardiovascular events occurred in patients with single ventricle, and were more frequent in older patients (33 vs 27 y.o., p = 0.03). Obstetric complications occurred in 20% of the cases. Small for gestational age was diagnosed in 33%.The mean birth weight was 1868 ± 641 g at a mean gestational age of 34 ± 3WG, and 76% of newborns were premature. Neonatal death occurred in 4/40 live births. No CHD was diagnosed in the offspring. Conclusion: Women with cyanotic CHD can go through pregnancy with a low risk for themselves during pregnancy and postpartum period. However, cyanotic CHD is associated with a high incidence of fetal and neonatal complications, with high rates of premature births, small gestational for age neonates and neonatal death. Close fetal monitoring and management in referral centers are required in this complex cardiac condition.

AIMS:To evaluate the benefit of adding Losartan to baseline therapy in patients with Marfan syndrome (MFS). METHODS AND RESULTS:A double-blind, randomized, multi-centre, placebo-controlled, add on trial comparing Losartan (50 mg when <50 kg, 100 mg otherwise) vs. placebo in patients with MFS according to Ghent criteria, age >10 years old, and receiving standard therapy. 303 patients, mean age 29.9 years old, were randomized. The two groups were similar at baseline, 86% receiving β-blocker therapy. The median follow-up was 3.5 years. The evolution of aortic diameter at the level of the sinuses of Valsalva was not modified by the adjunction of Losartan, with a mean increase in aortic diameter at the level of the sinuses of Valsalva of 0.44 mm/year (s.e. = 0.07) (-0.043 z/year, s.e. = 0.04) in patients receiving Losartan and 0.51 mm/year (s.e. = 0.06) (-0.01 z/year, s.e. = 0.03) in those receiving placebo (P = 0.36 for the comparison on slopes in millimeter per year and P = 0.69 for the comparison on slopes on z-scores). Patients receiving Losartan had a slight but significant decrease in systolic and diastolic blood pressure throughout the study (5 mmHg). During the study period, aortic surgery was performed in 28 patients (15 Losartan, 13 placebo), death occurred in 3 patients [0 Losartan, 3 placebo, sudden death (1) suicide (1) oesophagus cancer (1)]. CONCLUSION:Losartan was able to decrease blood pressure in patients with MFS but not to limit aortic dilatation during a 3-year period in patients >10 years old. β-Blocker therapy alone should therefore remain the standard first line therapy in these patients.

To assess health-related quality of life (QoL) in patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) and correlations with clinical status. This cross-sectional study included PAH-CHD patients in 14 centers in France. QoL was self-reported with a generic questionnaire (SF-36) and a PH-specific questionnaire (CAMPHOR). Patients filled out the Hospital Anxiety and Depression Scale (HADS) questionnaire. Main clinical data were collected. 200 patients were included (mean age 43±SD15.7 years, range 15 to 86 years, 70% female), and were classified as Eisenmenger syndromes (73.5%), PAH associated with systemic to pulmonary shunts (13%), PAH associated with small defects (3.5%) and PAH after corrective cardiac surgery (10%). At inclusion, 76.5% patients were receiving PAH-specific treatments. All component scores of both QoL questionnaires showed degradation vs healthy population standard scores. QoL scores were lower in females than in males for all dimensions of both questionnaires (p<0.05). QoL scores were independent of the type of PAH-CHD but significantly depended on NYHA class even after gender adjustment. In a multivariate analysis, variables significantly affecting QoL included NYHA class, six-minute walk distance, HADS, gender, recent stressful event, and more than one hospitalization within the past 12 months. This study showed degradation of QoL in a large cohort of PAH-CHD patients with both generic and specific questionnaires. QoL was correlated with NYHA class but not with the type of PAH-CHD.

The use of COAGUCHEK XS® (Roche Diagnostics), an INR home measuring device, was authorised by the French Health High Authority on June 2008 for children. Nevertheless, there are few data on safety and effectiveness of patients self management particularly in children. Since 2008, 23 children (mean age: 9 y; 16 males, 7 females) and their families were trained to INR self testing and self management of vitamin K antagonists (VKA) (acenocoumarol: n=10, fluindione : n=9, warfarin: n=4). INR controls (self testing or lab) were made at expected dates established by the french law. Additional measurements were authorised in risky situations (illness, hyperthermia, forgetting VKA treatment, bleeding, etc…). Drug dose adaptation was made either by the family or by the health team if needed. To evaluate safety and efficacy in families performing self management in our centre. Time in therapeutic range (TTR), severe haemorrhage (needing hospitalization and/or blood transfusion) and thrombosis recurrence were observed. Mean follow-up time was 529 days [1.5 y; range 0.3-2.5y]. Mean TTR was 68.53% and was 90.14% when tolerance range was applied. There was no severe haemorrhage or thrombosis recurrence during follow-up and INR >5 were 0.5% (8/1604 measurements). Lastly, 3.5% additional measurements were performed by the families. VKA self management using COAGUCHEK XS® was safe and effective in our centre. Clinical studies with larger sample and cost-effectiveness considerations are required.

We analyzed 16 cases of hypoplastic left heart syndrome (HLHS) submitted to the multidisciplinary center at Rennes Teaching Hospital from 2006 to 2010 for prenatal diagnosis. The information given to parents at the moment of choice is capital for them to make their own decision: in our team the real choice for parents stands between termination of pregnancy (TOP) and palliative care (PC). The Norwood procedure is rarely proposed to parents in France and it is performed in very few centers. Heart transplant is never proposed nor done at this age. The objectives of our study were to understand the reasons for the choice of PC, take stock of our experience of PC, and relate the benefits but also the disadvantages of PC. Over the 16 patients whose fetus had HLHS, 9 requested TOP, while 7 others wanted to live their pregnancy and meet their child at birth, therefore requesting neonatal PC. No family asked for the Norwood procedure. Four children died within the first days (D1, D2, D4, D9), 2 others died at 5 and 7 months, 1 child was operated on for coarctation of the aorta (unknown before birth) and is still alive 1.5 years later. Maternal motivations to continue the pregnancy were clearly described for 2 of the 7 cases: religious prohibition of TOP in 1 case, negative experiences of previous abortions in the second case. In another case, the parents hesitated between PC and Norwood surgery. For the other women, the reasons were less clearly expressed. In our series, HLHS is the first indication for PC from prenatal diagnosis (7/16 cases in the same period) while in the literature, heart diseases are the second cause of TOP after the neurological causes. The overrepresentation of this pathology in the families who opt for PC may be due to the unconscious image that both professionals and families have of HLHS: severity of an inevitably fatal disease, rapid postnatal death, and no suffering. Our study may change this view: a child was in fact carrying a curable defect which was discovered 12 days after birth, 2 children died at 5 and 7 months, and 5 of 6 children had major analgesics at the end of life. Nevertheless, the families were supported and followed by the PC network, except 1. who ruptured all contacts in a context of presumed intense suffering, but the other 6 do not regret their choice despite the difficulties. (C) 2012 Elsevier Masson SAS. All rights reserved.