Search

Treatment for pulmonary arterial hypertension (PAH) has been underpinned by single-agent therapy to which concomitant drugs are added sequentially when pre-defined treatment goals are not met.This retrospective analysis of real-world clinical data in 97 patients with newly diagnosed PAH (86% in New York Heart Association functional class III−IV) explored initial dual oral combination treatment with bosentan plus sildenafil (n=61), bosentan plus tadalafil (n=17), ambrisentan plus tadalafil (n=11) or ambrisentan plus sildenafil (n=8).All regimens were associated with significant improvements in functional class, exercise capacity, dyspnoea and haemodynamic indices after 4 months of therapy. Over a median follow-up period of 30 months, 75 (82%) patients were still alive, 53 (71%) of whom received only dual oral combination therapy. Overall survival rates were 97%, 94% and 83% at 1, 2 and 3 years, respectively, and 96%, 94% and 84%, respectively, for the patients with idiopathic PAH, heritable PAH and anorexigen-induced PAH. Expected survival rates calculated from the French equation for the latter were 86%, 75% and 66% at 1, 2 and 3 years, respectively.Initial combination of oral PAH-targeted medications may offer clinical benefits, especially in PAH patients with severe haemodynamic impairment.

Objective Kawasaki disease (KD) is a vasculitis that mostly occurs in young children and rarely in adults. We analyzed the characteristics of adult-onset KD (AKD) in France. Methods We collected retrospective and prospective data for patients with a diagnosis of KD occurring after the age of 18 years. Cases were obtained via various French medical networks and identified from the international literature. Results We included 43 patients of AKD at 26 institution from 1992 to 2015, with mean (SD) age 30 (11) years (range 18–68) and sex ratio (M/F) 1.2; 34 patients met the American Heart Association criteria and 9 were incomplete AKD. The median time to diagnosis was 13 days (interquartile range 8–21). The main symptoms were fever (100%), exanthema (98%), changes in the extremities (91%), conjunctivitis (77%), oral cavity changes (89%), cervical adenitis (55%) and cardiac abnormalities (45%). Overall, 35% of patients showed large-vessel vasculitis: coronary vasculitis (26%) and coronary aneurysm (19%). Treatment was mostly intravenous immunoglobulins (79%) and aspirin (81%). Four patients showed myocardial infarction due to coronary vasculitis, but none were treated with IVIg because of late diagnosis. After a median follow-up of 5 months (range 1–117), persistent aneurysm was noted in 9% of cases. Damage was significantly lower with early treatment than late or no treatment (p = 0.01). Conclusion Given the high frequency of cardiac involvement and complications in this series of AKD, diagnosis and treatment should not be delayed, and early IVIg treatment seems to improve the outcome

The prognostic importance of follow-up haemodynamics and the validity of multidimensional risk assessment are not well established for systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH).We assessed incident SSc-PAH patients to determine the association between clinical and haemodynamic variables at baseline and first follow-up right heart catheterisation (RHC) with transplant-free survival. RHC variables included cardiac index, stroke volume index (SVI), pulmonary arterial compliance and pulmonary vascular resistance. Risk assessment was performed according to the number of low-risk criteria: functional class I or II, 6-min walking distance (6MWD) >440 m, right atrial pressure −1·m−2.Transplant-free survival from diagnosis (n=513) was 87%, 55% and 35% at 1, 3 and 5 years, respectively. At baseline, 6MWD was the only independent predictor. A follow-up RHC was available for 353 patients (median interval 4.6 months, interquartile range 3.9–6.4 months). The 6MWD, functional class, cardiac index, SVI, pulmonary arterial compliance and pulmonary vascular resistance were independently associated with transplant-free survival at follow-up, with SVI performing better than other haemodynamic variables. 1-year outcomes were better with increasing number of low-risk criteria at baseline (area under the curve (AUC) 0.63, 95% CI 0.56–0.69) and at first follow-up (AUC 0.71, 95% CI 0.64–0.78).Follow-up haemodynamics and multidimensional risk assessment had greater prognostic significance than at baseline in SSc-PAH.

RésuméJustificationLes données décrivant l’hypertension artérielle pulmonaire chez l’enfant sont peu nombreuses.ObjectifsL’objectif a été de caractériser l’épidémiologie, la prise en charge, l’impact sur la qualité de vie et les conséquences de l’hypertension artérielle pulmonaire de l’enfant en excluant les patients avec une hypertension artérielle pulmonaire persistante du nouveau-né et ceux dont l’hypertension artérielle pulmonaire était causée par une cardiopathie congénitale.MéthodesDans cette étude non interventionnelle multicentrique, des enfants atteints d’hypertension artérielle pulmonaire ont été inclus et suivis prospectivement pendant 2 ans dans 21 centres français. La classe fonctionnelle OMS, la distance de marche de 6 minutes, la qualité de vie (questionnaire CHQ-PF50), les paramètres hémodynamiques et les échodopplers réalisés ont été évalués.RésultatsCinquante enfants d’âge moyen de 8,9 ± 5,4 ans ont été inclus de mai 2005 à juin 2006. La prévalence de l’hypertension artérielle pulmonaire a été estimée à 3,7 cas/million. Les patients avaient une hypertension artérielle pulmonaire idiopathique (60 %), familiale (10 %), associée avec une cardiopathie congénitale qui n’était pas la cause de l’hypertension artérielle pulmonaire (24 %), associée à une connectivite (4 %) ou à une hypertension portale (2 %). Pendant le suivi, le nombre d’associations de médicaments spécifiques de l’hypertension artérielle pulmonaire prescrit a augmenté (44 % des patients contre 22 % à l’inclusion). La majorité des patients est restée stable en ce qui concerne l’état clinique, le test de marche de 6 minutes et la qualité de vie. La survie à 1 et 2 ans a été estimée à 86 % (intervalle de confiance à 95 % : [76, 96]) et 82 % (95 % intervalle de confiance : [71, 93]).ConclusionsChez l’enfant, dans la majorité des cas, les hypertensions artérielles pulmonaires sont idiopathiques ou familiales. Un groupe spécifique d’hypertension artérielle pulmonaire concomitante d’une cardiopathie congénitale a été identifié et ressemble à une hypertension artérielle pulmonaire idiopathique. Les associations de traitements spécifiques de l’HTAP peuvent avoir contribué à la stabilité de la maladie et à une meilleure survie.SummaryJustificationThere is few data describing pulmonary arterial hypertension in children.ObjectivesThe objective was to describe the epidemiology and management of pulmonary arterial hypertension (PAH) in children, as well as its effects on the quality of life and its consequences, excluding patients with persistent pulmonary hypertension of the newborn and those with pulmonary arterial hypertension due to congenital heart disease.MethodsThis multicenter non interventional study included children with pulmonary arterial hypertension who were prospectively followed for two years in 21 French centres. The WHO functional classification, the 6-minute walk distance, the quality of life (CHQ-PF50 questionnaire), the hemodynamics parameters and echodoppler performed were evaluated.ResultsFifty children with a mean age of 8.9 ± 5.4 years were included from May 2005 to June 2006. The prevalence of pulmonary arterial hypertension was estimated at 3.7 cases per million. The patients had the following types of pulmonary arterial hypertension: idiopathic (60%), familial (10%), associated with congenital heart disease that was not the cause of the pulmonary hypertension (24%), associated with a connective-tissue disease (4%) or with portal hypertension (2%). During follow-up there was an increase in the number of drugs prescribed specifically for pulmonary arterial hypertension (44% patients versus 22% at inclusion). The clinical status, 6-minute walk test and quality of life of the majority of patients remained stable. The survival at one and at two years was estimated at 86% [95% confidence interval (76, 96)] and 82% [95% confidence interval (71, 93)].ConclusionsThe majority of cases of pulmonary arterial hypertension in children are idiopathic / familial. A specific group of pulmonary arterial hypertension occurring with congenital heart disease has been identified and resembles idiopathic pulmonary arterial hypertension. The use of specific treatments for PAH may contribute to the stability of the disease and to better survival.

Kawasaki disease (KD) is an acute multisystemic vasculitis occurring predominantly in children and rarely in adults. Diagnosis is made clinically using diagnostic guidelines; no specific test is available. "Incomplete" KD is a more recent concept, which refers to patients with fever lasting > or =5 days and 2 or 3 clinical criteria (rash, conjunctivitis, oral mucosal changes, changes of extremities, adenopathy), without reasonable explanation for the illness. To describe the clinical and laboratory features of classical (or "complete") KD, and incomplete KD in adults, we report 10 cases of adult KD, including 6 patients who fulfilled the criteria for incomplete KD, diagnosed either at presentation (n = 4) or retrospectively (n = 2). At the time of clinical presentation, complete KD was diagnosed in 4 patients, while 4 patients fulfilled the criteria for incomplete KD. For 3 of the 4 patients with incomplete KD, presence of severe inflammation, laboratory findings (hypoalbuminemia, anemia, elevation of alanine aminotransferase, thrombocytosis after 7 days, white blood cell count > or =15,000/mm, and urine > or =10 white blood cell/high power field), or echocardiogram findings were consistent with the diagnosis. In 2 patients, the diagnosis of KD was made retrospectively in the presence of myocardial infarction due to coronary aneurysms, after an undiagnosed medical history evocative of incomplete KD. Seven patients received intravenous immunoglobulins (IVIG), after a mean delay of 12.5 days, which appeared to shorten the course of the disease. This relatively large series of adult KD highlights the existence of incomplete KD in adults and suggests that the algorithm proposed by a multidisciplinary committee of experts to diagnose incomplete KD in children could be useful in adults. Further studies are needed to determinate whether prompt IVIG may avoid artery sequelae in adult patients with complete or incomplete KD.

SummaryBackgroundIntrastent thrombosis, while rare, has a poor prognosis. Strut non-coverage is one causal factor, especially in cases of resistance to or premature discontinuation of dual antiplatelet therapy.AimTo compare neointimal coverage with paclitaxel and zotarolimus drug-eluting stents, using optical coherence tomography (OCT).MethodsTwenty-two drug-eluting stents (11 paclitaxel-eluting stents and 11 zotarolimus-eluting stents) were examined by OCT, 6 months after implantation. Mean neointimal strut-coverage thickness and percentage neointimal hyperplasia were measured every millimetre. On each OCT image, struts were classified into one of four categories: well-apposed to vessel wall with apparent neointimal coverage; well-apposed to vessel wall without neointimal coverage; malapposed to the vessel wall; or located on a major side branch.ResultsOCT analysis showed a lower percentage of neointimal hyperplasia with paclitaxel-eluting stents than with zotarolimus-eluting stents (17% vs 38% and mean thickness 154μm vs 333μm, respectively; p

Summary Background Percutaneous closure of large persistent ductus arteriosus using the Amplatzer ® duct occluder is an alternative to surgery. However, this device is not recommended in infants weighing less than 6 kg. Aim To evaluate the safety and effectiveness of this procedure in low-body-weight infants. Methods We reviewed retrospectively data for infants weighing less or equal to 6 kg who underwent percutaneous closure of significant persistent ductus arteriosus using the Amplatzer ® duct occluder in France between 1998 and 2007. Results Data for 58 patients (mean weight: 5 kg, range: 3.4–6; mean age: 5.5 months, range: 2.1–15.3) were reviewed. Mean angiographic persistent ductus arteriosus minimal diameter was 3.7 mm (range: 1–7.5). Implantation of the Amplatzer ® duct occluder was successful in 89.7% of cases. In six (10.3%) patients, the device was not implanted because it would have led to significant aortic obstruction. One procedure-related death occurred in a 4 kg infant (1.7%). Major and minor complications occurred in 6.9 and 31.0% of patients, respectively. Persistent ductus arteriosus diameter greater than 3.7 mm, type C (tubular shape) and diameter/patient weight ratio greater than 0.91 were significantly associated with an unsuccessful procedure and/or major complications. During a median 10-month follow-up, no late device embolization occurred. Conclusions Although percutaneous closure of significant persistent ductus arteriosus with the Amplatzer ® duct occluder is effective in low-body-weight infants, the level and severity of complications indicate surgery as first-line treatment, at least until further studies are done to assess the safety and effectiveness of the new Amplatzer ® duct occluder II in low-body-weight infants.

We present an unusual fortuitously discovered case of atresia of the left inferior pulmonary vein with drainage via anastomosis to the left upper pulmonary vein and the left atrium. Atresia of the pulmonary veins is a very rare anomaly that results from defective incorporation of the pulmonary venous system into the left atrium. The initial diagnosis, drawn from plain radiographs, was confirmed by cardiac catheterization and pulmonary angiography. The appearance of clinical signs, prognosis, and the need for treatment depend on how well substitute drainage is performed.

Summary Introduction Thromboembolic accidents and haemorrhage are the main complications observed during long-term follow-up of mechanical heart valve patients. Several suggestions for improving anticoagulation quality have been made, including international normalised ratio (INR) self-monitoring. Objectives We report the preliminary results of a single-centre, open, randomised study (scheduled population of 200 patients), which compares monthly laboratory monitoring (group A) versus weekly self-monitoring of INR (group B). The primary aim is INR stability improvement within the target range, and the secondary aim is adverse events reduction. Patients and methods Between May 2004 and June 2005, 67 patients with an average age of 56.6 years (± 9.6), were enrolled in the study (group A: 34 patients, group B: 33 patients). The mean follow-up was 47 weeks (± 11.5). The two groups differed only in the sex ratio (44.1 and 21.2% of women in groups A and B respectively, p = 0.0459). Mechanical heart valves were aortic in 73% of patients, mitral in 13.5%, and multiple in 13.5%. Sixty-five patients (97%) were treated with fluindione, the others with acenocoumarol. The intraclass correlation coefficient between the self- and laboratory-monitored INR was 0.75. Results The time spent in the INR target range (group A: 53 ± 19%, group B: 57 ± −19%, p = 0.45) and the time spent in the INR therapeutic range, between 2 and 4.5, (group A: 86 ± 14%, group B: 91 ± 7%, p = 0.07) are longer in group B, but not significantly so. For patients outside the range, the absolute mean deviation of INR from the target or therapeutic range (range standardized between 0 and 100) is lower for the self-monitoring group (41.1 ± 39.3 and 11.27 ± 11.2) than for the control group (62.4 ± 72.6 and 39.2 ± 52.8). This difference is significant ( p = 0.0004 and p = 0.0005). Eighteen adverse events were reported: 17 haemorrhages, 13 in group A (9 mild, 4 serious) and four in group B (all mild), and one sudden death in group B, two days after the patient's discharge. No thromboembolic events were reported. Six patients (8.8 %), 3 in each group, dropped out of the study. Conclusion This first study evaluating INR self-monitoring in France shows that this method leads to better stability of the INR within the target range. On the basis of these preliminary data, this appears to be related to a decrease in serious haemorrhages (11.8% serious haemorrhage cases in group A versus 0% in group B, p = 0.06, NS).

Percutaneous Patent Foramen Ovale (PFO) closure after paradoxical embolism has become established as a safe, effective and validated procedure. The use of dedicated devices by experienced operators allows for low complication rates and good clinical results in the prevention of paradoxical embolism recurrence. This has led to a widespread use of the technique. However, late complications have been reported after the implantation of different types of devices. We report the first case of cardiac tamponade due to atrial wall erosion, which occurred three months after the implantation of a STARflex device (Nitinol Medical Technologies, Boston, Massachusetts, USA) in a 57 year-old-patient Transoesophageal echocardiographic images and surgical views of the perforation related to the device are presented. This report describes treatment of a late complication that arose following implantation of a STARflex device.

Introduction: Kawasaki disease (KD) is a vasculitis that occurs mostly among children and exceptionally in adults. We report data from a French observatory of adult KD. Patients and methods: Adult patients diagnosed with KD in 16 French centers were included. Patients were classified as complete KD or incomplete KD according to IKDC or probable KD. Results: We included 24 patients with a median age of 29 years (22-39) and a sex ratio (M / F) 2.42, 12 complete KD, 9 incomplete KD and 3 probable KD without any other cause. Time to diagnosis was 13 days (10-20.5). Main events were: fever (100%), extremities changes (21/24, 87.5%), rash (22/24, 92%), conjunctivitis (16/24, 16, 66%), cheilitis (15/24, 63%), strawberry tongue (11/24, 46%), adenopathy (10/24, 42%), cardiac abnormalities (11/24, 46%), cardiogenic shock (n = 1), myo-pericarditis (n = 3) and left heart failure (n = 1). Median CRP was 228mg/L (166-311), SGOT: 68 IU/L (51-139), SGPT: 125 IU/L (69-190), platelets 372 G/L (209-630) and leukocytes 16 G/L (8.3-20). Cardiac involvement was researched in 23 patients (96%) by achieving: echocardiography (20/24), coronary scanners (6/24), coronary angiography (5/24), cardiac MRI (2/24) and stress tests (2/24). An arteritic vascular disease was found in 11 patients (46%): coronary aneurysms (8/24, 33%), coronary arteritis (10/24; 42%) and peripheral arteritis (2/24, 8.3%) with acute lower limb ischemia (1/24, 4.2%) and splenic infarction (1/24, 4.2%). Patients received: intravenous immunoglobulin (17/24; 71%): aspirin (21/24, 88%). After 6 months, it persisted 5 aneurysm (20.8%). Complications noticed during the last follow-up were: heart failure (1/24, 4.3%), aneurysm (3/24, 12.5%). Conclusion: The adult KD is a rare disease that can have bad prognosis in short or long term and leave irreversible damage. The high rate of cardiac complication could be due to the long diagnosis delay, the absence of the gold standard treatment in 30% of cases or a selectional bias due to the difficulty to diagnose this disease in adulthood.

Intrahepatic portosystemic anastomoses are macroscopic communications between the venous portal system and the systemic circulation and located partly in the liver. We report 4 new cases of type II shunts, which illustrate the circumstances of the diagnosis of these exceptional anomalies. For 2 children, the diagnosis was done antenataly by US and spontaneous involution in a few months was observed. In the third case the malformation was evidenced fortuitously at 3 weeks of life, and this 6-year-old child remains completely asymptomatic so far. Then, in the fourth case, a cerebral venous thrombosis was fortuitously and antenatally evidenced in an otherwise uneventful pregnancy and portosystemic shunt was demonstrated postnataly in the extensive work up of the neonate.

We describe a case of recurrent Kawasaki disease (KD) in a non-Asian 6-year-old boy who had been diagnosed with typical KD without cardiac involvement at age 3 years. He was admitted to the PICU 3 years later for heart failure, hypotension, and deterioration of his general condition. Ultrasonography revealed left ventricular dysfunction with a 44% ejection fraction and grade I mitral valve failure without coronary artery involvement. Subsequent observation of hyperemic conjunctiva, bilateral cervical adenopathies with erythematous skin (normal neck ultrasound and computed axial tomography findings), peeling of the fingertips at day 8 of the illness, and occurrence of an inflammatory syndrome led to a diagnosis of incomplete recurrent KD with a clinical picture of Kawasaki shock syndrome (KSS). Clinical improvement was rapidly obtained after intravenous immunoglobulin and intravenous corticosteroid therapy (30 mg/kg per day for 3 subsequent days). Left ventricular function gradually improved, with ultrasound returning to normal after 3 months. Diagnosis was difficult to establish because of the recurrence of the disease and the incomplete clinical picture, with clinical features of KSS. Physicians need to be aware of these pitfalls in the management of patients with clinical signs of KD.

Resume Le thrombus flottant de la crosse aortique est une cause rare et souvent meconnue d’evenements emboliques peripheriques. Nous rapportons l’observation d’une patiente presentant des manifestations emboliques peripheriques recidivantes : ischemie aigue du membre superieur gauche et accident vasculaire cerebral transitoire. Le bilan (echocardiographie transœsophagienne et angio TDM) a mis en evidence un thrombus de 12 mm de l’arche aortique. L’evolution a ete bonne sous traitement anticoagulant. Ce diagnostic ne doit pas etre meconnu dans le bilan d’une pathologie emboligene, sous peine de lourdes sequelles fonctionnelles causees par un retard diagnostique important.

Although varicella is most often a benign and self-limited disease of childhood, it can be associated with a variety of serious and potential lethal complications. Especially, the incidence of severe infectious complications caused by group A streptococci has been increasing over the last years. We report the case of a previously healthy young boy with an aortic bicuspidy who developed a varicella complicated by endocarditis due to group A streptococcus, and a haemophagocytic syndrome. A favorable outcome was obtained after an early valvular replacement and 6 weeks of intravenous antibiotics.

We report a case with very early antenatal diagnosis of aortico-left ventricular tunnel (ALVT) at 22 weeks of pregnancy. Early recognition of ALVT by antenatal ultrasound allows prompt neonatal management and avoidance of harmful aortic valve regurgitation. The present case is unique because of the conjunction of very early antenatal diagnosis, prompt postnatal management, early surgical repair on the sixth day of life, direct closure from the aorta of the aortic orifice only, and optimal postoperative course with excellent mid-term result.

Introduction Transcatheter closure of ASD is now proposed as first line treatment for the elderly patients. Purpose The aim of our study is to evaluating the transcatheter closure of ASD in patients older than 60 years. Methods The records of 41 patients (37 women, 4 men) who are over 60 years (69.88±6 years, range 61-82 years), referred between April 1998 and December 2010 for transcatheter closure of secundum ASD, were retrospectively reviewed Results ASD was discovered during the assessment of patients with dyspnea (17) or arrhythmia (17). Average age at time of diagnosis was 62.4±14.89 years (range 14-82 years). 37.8% of cases had a delayed diagnosis. At time of the procedure, 19 patients (46.3%) had supraventricular arrhythmia and 82.9% of patients were dyspneic. Shunt ratio was 2.50±0.66, defect size 19.67±6.76 mm, stretched diameter 24.36 mm±5.87, device diameter of 24.49 mm±6.58. One patient was recused, because of increased left atrial pressure at occlusion test. Fluoroscopy time was 7.01±4.41 min. Success rate is 97.5%. Complete closure rate at one day and one month was 84.6% and 94.9% respectively. Systolic pulmonary pressure decreased from 49.37 to 34,58 mmHg at one month. Hospital stay was 3.58 days ± 2.71. Periprocedural complication rate was 12.2%. 2 complications were major: one death by esophageal hematoma, and one oropharyngeal bleeding, and 3 minors: 3 femoral arteriovenous fistulas. At late follow-up (34±44 months, range 1month to 12 years), 34 patients were in stage one, 4 recurred supraventricular arrhythmia, 1 needed pace maker for sinus node dysfunction. Conclusion Transcatheter closure of ASD in ederly patients is effective. It does not change rhythmic status but allows symptomatic improvement.

Secundum-type atrial septal defects (ASDII) account for approximately 10% of all congenital heart defects (CHD) and are associated with a familial risk. Mutations in transcription factors represent a genetic source for ASDII. Yet, little is known about the role of mutations in sarcomeric genes in ASDII etiology. To assess the role of sarcomeric genes in patients with inherited ASDII, we analyzed 13 sarcomeric genes (MYH7, MYBPC3, TNNT2, TCAP, TNNI3, MYH6, TPM1, MYL2, CSRP3, ACTC1, MYL3, TNNC1, and TTN kinase region) in 31 patients with familial ASDII using array-based resequencing. Genotyping of family relatives and control subjects as well as structural and homology analyses were used to evaluate the pathogenic impact of novel non-synonymous gene variants. Three novel missense mutations were found in the MYH6 gene encoding alpha-myosin heavy chain (R17H, C539R, and K543R). These mutations co-segregated with CHD in the families and were absent in 370 control alleles. Interestingly, all three MYH6 mutations are located in a highly conserved region of the alpha-myosin motor domain, which is involved in myosin-actin interaction. In addition, the cardiomyopathy related MYH6-A1004S and the MYBPC3-A833T mutations were also found in one and two unrelated subjects with ASDII, respectively. No mutations were found in the 11 other sarcomeric genes analyzed. The study indicates that sarcomeric gene mutations may represent a so far underestimated genetic source for familial recurrence of ASDII. In particular, perturbations in the MYH6 head domain seem to play a major role in the genetic origin of familial ASDII.

International audience; Dilated Cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. More than 30 genes have been reported to cause DCM. To provide new insights into the pathophysiology of dilated cardiomyopathy, a mutational screening on 4 DCM-causing genes (MYH7, TNNT2, TNNI3 and LMNA) was performed in a cohort of 105 unrelated DCM (64 familial cases and 41 sporadic cases) using a High Resolution Melting (HRM)/sequencing strategy. Screening of a highly conserved arginine/serine (RS)-rich region in exon 9 of RBM20 was also performed. Nineteen different mutations were identified in 20 index patients (19%), including 10 novels. These included 8 LMNA variants in 9 (8.6%) probands, 5 TNNT2 variants in 5 probands (4.8%), 4 MYH7 variants in 3 probands (3.8%), 1 TNNI3 variant in 1 proband (0.9%), and 1 RBM20 variant in 1 proband (0.9%). One proband was double-heterozygous. LMNA mutations represent the most prevalent genetic DCM cause. Most patients carrying LMNA mutations exhibit conduction system defects and/or cardiac arrhythmias. Our study also showed than prevalence of mutations affecting TNNI3 or the (RS)-rich region of RBM20 is lower than 1%. The discovery of novel DCM mutations is crucial for clinical management of patients and their families because pre-symptomatic diagnosis is possible and precocious intervention could prevent or ameliorate the prognosis.

In this single-center French study, the conventional management of patients receiving vitamin K antagonists (VKAs) was compared with an International Normalized Ratio (INR) self-testing program. The aim was to determine the reliability of self-testing devices, and to estimate the variability of the self-measured INR within the therapeutic and target range.A total of 206 patients who had undergone valve replacement with a mechanical prosthesis, with or without myocardial revascularization, between May 2004 and September 2007 was randomized into two groups. Group 1 patients (n = 103) underwent INR monitoring at a laboratory, while Group 2 patients (n = 103) underwent self-testing INR using either the CoaguChek (Roche) (Group 2A; n = 55) or INRatio (Hemosense) (Group 2B; n = 48) system. Patients in Group 1 underwent at least once-monthly INR measurement, while those in Group 2 carried out once-weekly self-testing, and also underwent once-monthly INR measurement at the laboratory. The large majority of patients (97.9%) were treated with fluindione.The mean follow up period was 49.0 +/- 10.3 weeks. Self-testing was reliable, with a correlation coefficient between device- and laboratory-measured INRs of 0.80 [CI: 0.78, 0.82] (p0.0001). The proportion of time spent within the INR target range was significantly higher for Group 2 (61.5 +/- 19.3% versus 55.5 +/- 19.9%; p0.05), while the absolute mean deviation of INR from the target range was higher in Group 1 (60.1 +/- 70.2% versus 47.4 +/- 51.5%). Adverse events were reported by seven patients in Group 1, but by no patients in Group 2 (p0.01).INR self-testing devices are reliable and beneficial. Moreover, INR self-monitoring allows an enhanced stability within a target range, and also helps to prevent serious postoperative complications.

Background Combined oral contraceptives (COC) increase the risk of venous thromboembolism (VTE), but the risk of recurrent VTE is not precisely determined. In this retrospective cohort study, we sought the risk factors for recurrence after a first VTE that occurred in women taking COC. Study Design Time-to-event analysis was done with Kaplan–Meier estimates. In total, 172 patients were included (43% with pulmonary embolism): 82% had no other clinical risk factor for VTE. Results Among the 160 patients who stopped anticoagulation, the cumulative incidence of recurrent VTE was 5.1% after 1 year and 14.2% after 5 years. Significant factors associated with recurrence were renewed use of COC [hazard ratio (HR)=8.2 (2.1–32.2)], antiphospholipid syndrome [HR=4.1 (1.3–12.5)] and protein C deficiency or factor II G20210A [HR=2.7 (1.1–7)]. Pure-progestin contraception [HR=1.3 (0.5–3.0)] or factor V Leiden [HR=1.3 (0.5-3.4)] did not increase recurrence. Postsurgical VTE had a lower risk of recurrence [HR=0.1 (0.0–0.9)]. Conclusion Further studies are warranted to determine whether testing for antiphospholipid syndrome, protein C deficiency or the factor II G20210A could modify the duration of anticoagulation. This study confirms the safety of pure-progestin contraception.

International audience; Hypertrophic Cardiomyopathy (HCM), a common and clinically heterogeneous disease characterized by unexplained ventricular myocardial hypertrophy and a high risk of sudden cardiac death, is mostly caused by mutations in sarcomeric genes but modifiers genes may also modulate the phenotypic expression of HCM mutations. The aim of the current study was to report the frequency of single and multiple gene mutations in a large French cohort of HCM patients and to evaluate the influence of polymorphisms previously suggested to be potential disease modifiers in this myocardial pathology. We report the molecular screening of 192 unrelated HCM patients using denaturing high-performance liquid chromatography/sequencing analysis of the MYBPC3, MYH7, TNNT2 and TNNI3 genes. Genotyping of 6 gene polymorphisms previously reported as putative HCM modifiers (5 RAAS polymorphisms and TNF-α -308 G/A) was also performed. Seventy-five mutations were identified in 92 index patients (48%); 32 were novel. MYBPC3 mutations (25%) represent the most prevalent cause of inherited HCM whereas MYH7 mutations (12%) rank second in the pathogenesis. The onset age was older in patients carrying MYBPC3 mutations than in those with MYH7 mutations. The MYBPC3 IVS20-2A>G splice mutation was identified in 7% of our HCM population. Multiple gene mutations were identified in 9 probands (5%), highlighting the importance of screening other HCM-causing genes even after a first mutation has been identified, particularly in young patients with a severe phenotype. No single or cumulative genetic modifier effect could be evidenced in this HCM cohort.

International audience; BACKGROUND: Limited data are available describing paediatric pulmonary arterial hypertension. AIMS: To characterize the epidemiology, management and impact on quality of life and outcome of paediatric pulmonary arterial hypertension, excluding persistent pulmonary hypertension of the newborn and pulmonary arterial hypertension caused by congenital heart disease. METHODS: In this multicentre study, children with pulmonary arterial hypertension were included and followed prospectively for two years at 21 referral centres in France. WHO functional class, 6-minute walk distance and quality of life (CHQ-PF50 questionnaire) were evaluated. RESULTS: Fifty children were included with a mean age of 8.9 +/- 5.4 years from May 2005 until June 2006. The estimated prevalence for pulmonary arterial hypertension was 3.7 cases/million. Patients had idiopathic pulmonary arterial hypertension (60%), familial pulmonary arterial hypertension (10%), pulmonary arterial hypertension associated with, but not caused by, congenital heart disease (24%), pulmonary arterial hypertension associated with connective tissue disease (4%) or portal hypertension (2%). During follow-up, the combination of pulmonary arterial hypertension-specific therapies was increasingly prescribed (44% patients versus 22% at inclusion). Patients remained stable regarding clinical status, 6-minute walk distance and quality of life. Survival estimates after one and two years were 86% (95% CI 76, 96) and 82% (95% CI 71, 93), respectively. CONCLUSIONS: In children, idiopathic/familial pulmonary arterial hypertension accounts for the majority of cases. A specific pulmonary arterial hypertension group in conjunction with congenital heart disease can be identified that resembles patients with idiopathic pulmonary arterial hypertension. Combined pulmonary arterial hypertension-specific therapies may have contributed to disease stability and favourable survival.

Introduction Pulmonary arterial hypertension (PAH) is a devastating disease with poor survival but there are limited data describing its impact in the paediatric population. Objective The objectives of this national prospective registry were to collect clinical and epidemiological data and to investigate the outcome of children with PAH. Methods All consecutive patients Results Fifty patients were included between May 2005 and June 2006. Mean age at diagnosis was 8.7 ± 5.4 years and male/female ratio was 1/1. The prevalence of pediatric PAH was 4.2 cases/million. A history of prematurity, cancer and major surgery was noticed in respectively 19%, 6% and 4% of patients. At inclusion, 28% of patients were in WHO FC III or IV. Aetiology of PAH was idiopathic in 60%; familial in 10%, associated with but not due to CHD in 24%, related to connective tissue disease in 4% and to portal hypertension in 2%. Nine patients (018%) died during the 2-year follow up. Survival estimates at 1 and 2 years were 86% and 82%. Seventy three percents of patients improved or did not change WHO FC (n = 44). Patients remained stable regarding 6MWD (n = 25), hemodynamics (n = 11), and QoL (n = 19). During the 2-year follow-up, combination of PAH-specific therapies was increasingly prescribed (44% patients vs. 22% at inclusion). Conclusions This first national paediatric registry showed (1) the presence of multiple PAH aetiologies in children, that could be different from those seen in adults, (2) the association with other co-morbidities, and (3) the stabilization or even improvement in patient's condition with the therapeutic management recommended in the current era.

Spontaneous coronary artery dissection (SCAD) is a rare pathology, principally affecting young women free of atheroma risk factors. Its physiopathology remains little understood, and the prognosis for such acute coronary syndromes is poor, as they occur suddenly. Management is often difficult, and no guidelines exist. The present single-center retrospective study concerns 12 cases of SCAD occurring between 2001 and 2008 in female patients under the age of 60. Eleven patients survived, with a favorable long-term evolution. Only 2 had conservative medical therapy, the other 10 undergoing percutaneous coronary intervention (2 procedures involving a coronary artery bypass graft). On the basis of this series and data from the literature, we suggest a strategy to improve the often dire prognosis of SCAD. Emergency angiography to confirm diagnosis is essential. Treatment should be guided by the extent of the lesions, the myocardial ischemia and the hemodynamic status. Conservative medical therapy is a reasonable approach in the case of distal dissection or conserved coronary flow. Percutaneous coronary intervention is feasible in the acute phase to restore coronary perfusion and hemodynamic stability. Surgery – emergency bypass or assisted circulation – should be restricted to cases where percutaneous coronary intervention has failed or is impossible.

Occult cardiac injury following blunt trauma is more common than generally suspected. Myocardial contusion is not rare, however, it is generally a benign disorder which often remains undiagnosed. We report a case of a right atrial rupture after blunt chest trauma causing a tamponade. A 24-year-old man was involved in a violent car accident and he presented in a state of collapse. A multislice computed tomography indicated a pericardial effusion (Figure 1). A transthoracic echocardiography was performed and confirmed pericardial effusion which was hyperechoic (Figure 2, Movie 1). Concerns about a possible mass in the right atrium led to examination with transesophageal echocardiography (Figure 3, Movie 2) which revealed the presence of a voluminous mass in the right atrium. The patient successfully underwent cardiac surgery to remove the mass, identified as a blood clot, and to repair the atrial tear. The present case is of special interest because of the rarity of documented incidents of blunt chest trauma causing right atrial tear and illustrates the usefulness of transesophageal echocardiography in completing the diagnosis in the event of haemopericardium.

Background: Pulmonary arterial hypertension (PAH) is an orphan disease with a poor prognosis. Recent significant medical advances include the availability of PAH-targeted therapies as well as the publication of international guidelines and of a treatment algorithm. Epidemiology data relative to PAH are scarce, especially in the paediatric population. Based on the recent experience of a French PAH registry in the adult population, we set up the project to establish a similar registry dedicated to paediatric PAH in France.Methods: This multicentre, prospective, epidemiological and non-interventional study consists of a transversal phase (1‐year enrolment) and a longitudinal phase (2‐year follow-up). Patients < 18 years old followed in the investigational centres for PAH, and for whom data from right heart catheterization or Doppler echocardiography at the time of diagnosis are available, are eligible. All forms of PAH may be enrolled, except for persistent pulmonary hypertension of the newborn and w...

Platypnea orthodeoxia syndrome (POS) is a rare situation with hypoxia and breathlessness in the upright position recovering in the recumbent position. A mechanical inter-atrial septum distortion, causing redirection of flow from the right to the left atrium through a patent foramen ovale (PFO), despite normal pulmonary pressure, is suggested to explain POS. Prevalence of predisposing anatomical factors remain little known Methods All patients who underwent a PFO closure for a POS were retrospectively included from 2 CHU. Predisposing anatomical factors were investigated. Results 67 patients (Median age 72 y.o., interquartile range 61-80; 58.2% men) were included. All patients had dyspnea (76.2% NYHA III or IV, 53.7% under oxygen-therapy). The remaining patients had a refractory hypoxemia (38.2%) without POS. Most frequent predisposing anatomical factor was an enlarged or unwound aorta (n=29, 43.3% 95CI 31.2-56.0) with an aortic aneurysm in 25 patients (37.3%, 95CI 25.8-50.0). Other factors identified were pneumonectomy (n=8, 11.9% CI95 5.3-22.2), a history of cardiac surgery (n=7, 10.5%, 95CI 4.3-20.3), mechanical ventilation (n=6, 9.0% 95CI 3.4-18.5), kyphoscoliosis (n=4, 6.0% 95CI 1.7-14.6), hepatomegaly (n=4, 6.0% 95CI 1.7-14.6, 2 patients with hepato-renal polycystic disease, one hemochromatosis and one cirrhosis), right ventricle failure (n=2,3.0% 95CI 0.4-10.4), pericardial effusions (n=2,3.0% 95CI 0.4-10.4), right ventricle arrhythmogenic dysplasia (n=2,3.0% 95CI 0.4-10.4), diaphragmatic paralysis (n=1, 1.5% 95CI 0.1-8.0), carcinoid syndrome with tricuspid regurgitation (n=1, 1.5% 95CI 0.1-8.0), a right atrium pace-maker lead (n=1, 1.5% 95CI 0.1-8.0) and a tako-tsubo syndrome (n=1, 1.5% 95CI 0.1-8.0). Conclusion Aortic aneurysm and pneumonectomy are the most frequent situation leading to a POS. Other causes were observed such as hepato-renal polycystic kidney, or atrial pacemaker probe that may be underdiagnosed in clinical practice.

Platypnea orthodeoxia syndrome (POS) is a rare situation with hypoxia and breathlessness varying between upright and recumbent position. A mechanical inter-atrial septum distortion, causing redirection of flow from the right to the left atrium through a patent foramen ovale (PFO), despite normal pulmonary pressure, is suggested to explain POS. Prevalence of predisposing anatomical factors remain little known. Methods All patients who underwent a PFO closure for a POS were retrospectively included from 2 CHU. Aetiologies were investigated. Results 67 patients (Median age 72 y.o., interquartile 61-80; 58.2% men) were included. All patients had dyspnea (76.2% NYHA III or IV, 53.7% under oxygen-therapy). The remaining patients had a refractory hypoxemia (38.2%) without POS. The most frequent predisposing anatomical factor was an enlarged or unwound aorta (n=29, 43.3% 95CI 31.2-56.0) with an aortic aneurysm in 25 patients (37.3%, 95CI 25.8-50.0). Other factors identified were pneumonectomy (n=8, 11.9% CI95 5.3-22.2), a history of cardiac surgery (n=7, 10.5%, 95CI 4.3-20.3), mechanical ventilation (n=6, 9.0% 95CI 3.4-18.5), kyphoscoliosis (n=4, 6.0% 95CI 1.7-14.6), hepatomegaly (n=4, 6.0% 95CI 1.7-14.6, 2 patients with hepato-renal polycystic disease, one hemochromatosis and one cirrhosis), right ventricle failure (n=2,3.0% 95CI 0.4-10.4), pericardial effusions (n=2,3.0% 95CI 0.4-10.4), right ventricle arrhythmogenic dysplasia (n=2,3.0% 95CI 0.4-10.4), diaphragmatic paralysis (n=1, 1.5% 95CI 0.1-8.0), carcinoid syndrome with tricuspid regurgitation (n=1, 1.5% 95CI 0.1-8.0), a right atrium pace-maker lead (n=1, 1.5% 95CI 0.1-8.0) and a takotsubo syndrome (n=1, 1.5% 95CI 0.1-8.0). Conclusion Aortic aneurysm and pneumonectomy are the most frequent and well known situation leading to a POS. Other causes less known were observed such as hepato-renal polycystic kidney, or atrial pacemaker probe that may be underdiagnosed in clinical practice.

Background Kawasaki Disease (KD) diagnostic is based on clinical, laboratory and echocardiographic criteria. Coronary artery brightness has been proposed as a criterion for diagnosis KD at the acute phase, but it is qualitative and subjective. Evaluation depends on the experience of individual echocardiographers. Objectives Diagnostic value of quantitative evaluation of echogenicity of the coronary artery wall (CAW) in KD at the acute phase. Methods A retrospective case-control study was performed in Clermont-Ferrand university hospital. Echocardiograms of 0 to 18 years old children between January 2012 to January 2014 was enrolled: 19 KD confirmed, 14 acute febrile illness and 34 apyretic children with congenital heart disease without coronary disease. The value of echogenicity was evaluated in decibel on 2mm2 Regions Of Interest (ROI) using Q LAB software -Philips-. For each examination, precordial short axis cross-section at level of aortic valve, 3 ROI are placed at the coronary artery environment, 3 ROI at the proximal segment of the left or right CAW, and 3 ROI at the aorta. Quantitative evaluation of echogenicity of CAW was performed with the measurement differences between ROI. Intraobserver variability was 0.8. Results Echogenicity of right CAW was significantly higher in the acute phase of KD than the other groups - p = 0.004, area under curve ROC = 0.8 -. Also it has been observed for left CAW - p = 0.17 -. Debate and outcome This first study highlights the interest of echogenicity quantitative measure of CAW for KD diagnostic. Echogenicity of CAW might be helpful in diagnostic for atypical or incomplete KD. The reproducibility has to be confirmed by a prospective study with more children suspected of KD. Download : Download full-size image Abstract 0328 - Figure: Area under curve ROC of the CAW echogenicity

Aims The comparison of three imaging methods to determine which is the most accurate and reliable for the detection of right-to-left shunt. Methods and results One hundred and seven patients who were hospitalized for stroke underwent: a transthoracic echocardiography (TTE) using second harmonic, a transcranial Doppler (TCD) and a transesophageal echocardiography (TEE) from August 2003 to April 2004. All studies were recorded on a videotape and were studied by a physician blinded to the study. With TTE and TEE, we found 44 (41%) patent foramen ovales. All contrast tests were positive with TCD for these 44 patients. For two patients, the contrast test was positive only with TTE and TCD. We found four false negative contrast tests with TTE. Among the 63 patients who had a negative contrast test with TEE and TTE, the results were the same with TCD for 59 of them; we were not able to determine a cause for the four positive tests. Conclusion This study confirms that transesophageal echocardiography has limitations in the diagnosis of patent foramen ovale. In this study, the negative predictive value of transcranial Doppler was excellent. Therefore, this examination is able to exclude a patent foramen ovale with a high level of confidence.

Objectif Les immunoglobulines intra-veineuses (IG-IV) representent une therapeutique centrale en immunopathologie. Leur pharmacodynamie immunomodulatrice est encore imparfaitement comprise. Leur tolerance est bonne, malgre de frequents effets indesirables mineurs. Sujet Nous presentons deux cas d’anemie par hyperhemolyse (AH) induite par IG-IV, administrees pour maladie de Kawasaki. Resultats principaux Les caracteristiques de ces enfants etaient : fille, 2 ans, 12 kg, sans antecedent, dilatation coronaire moderee, groupe A+ ; garcon, 10 ans, 45 kg, sans antecedent, myopericardite, groupe A-. Les doses de PRIVIGEN etaient : 2 g/kg ×2 a 48H. L’anemie hemolytique a evolue comme suit : apparition a 3 et 5 jours du traitement ; bonne tolerance ; taux minimal d’hemoglobine a 6.5 et 8.4 g/dL ; pics synchrones de LDH a 482 et 1699 U/L, de reticulocytes a 480 et 461 G/L ; coombs positif ; traitement par corticosteroides a 2 et 1.5 mg/kg sans transfusion ; resolution en 5 et 4 jours. Conclusion L’AH, liee a une immunisation passive iatrogene, est un evenement indesirable rare qui necessite une surveillance du taux d’hemoglobine avant et apres administration d’IG-IV.

Contexte L’hyperechogenicite coronaire est un signe echographique evocateur de maladie de Kawasaki (MK), mais sa valeur diagnostique est affaiblie par sa subjectivite. Objectif evaluer la valeur diagnostique de la mesure echographique de l’echogenicite pour la MK. Materiel et methode Analyse retrospective des images echographiques d’enfants de 0 a 18 ans : 18 MK confirmee, 18 temoins febriles et 18 temoins apyretiques apparies sur l’âge. Echographies sur le meme appareil, 3 operateurs. Echogenicite mesuree par le logiciel Q Lab. Mesure du signal (en dB) pour des regions d’interet (ROI) de 2 mm2 : en coupe parasternale petit axe, 3 ROI sur le myocarde, 3 dans la paroi de la partie intermediaire de la coronaire droite (CD), 3 dans la paroi du tronc de la coronaire gauche (CG) et 3 au niveau de l’aorte (Ao). Resultats Pas de difference d’echogenicite du myocarde (p=0.7), de l’Ao (p=0.4) ni de la CG (p=0.4). En revanche, la CD etait plus echogene chez les enfants ayant une MK que chez les 2 groupes de temoins (p Discussion et conclusion La reproductibilite de la mesure de l’echogenicite de la CD doit etre confirmee avant une etude prospective diagnostique et pronostique chez des enfants suspects de MK.

We report a case of a 14-month-old girl who was treated for acute lymphoblastic leukemia but died from interstitial alveolitis associated with foreign body vasculitis. This respiratory complication arose 3 months after an allogenic bone marrow transplant. No infectious agents (bacteria, virus, or parasite) were isolated from bronchial or lung tissue samples. Respiratory complications after chemotherapy are reviewed as well as the potential origin of the intravascular foreign bodies. Pediatr. Pulmonol. 1997; 23:382–385. © 1997 Wiley-Liss, Inc.

Le syndrome d'Eisenmenger (SE) est habituellement bien tolere pendant l'enfance et l'adolescence. Sa prise en charge necessite une experience a la fois dans le domaine de l'hypertension arterielle pulmonaire et dans celui des cardiopathies congenitales pour permettre: - la mise en route d'un traitement specifique de l'hypertension arterielle pulmonaire (HTAP), en fonction de la gene fonctionnelle du patient, parfois difficile a quantifier ; - la prevention et la prise en charge rapide des complications.

Objectifs Le suivi des Fallot operes repose sur la determination des volumes ventriculaires droits (VD), pouvant faire discuter une reprise chirurgicale. L’IRM est l’imagerie de reference. L’echographie 2D est notamment mise en defaut lors de dilatations VD massives. Materiels et methodes Comparaison IRM/echo 3D pour la determination des volumes VD chez 14 Fallot operes. Resultats Les 2 methodes concordaient pour les patients presentant une dilatation VD moderee. Une sous-estimation echographique etait retrouvee chez les patients porteurs d’une dilatation VD importante (superieure a 150 ml/m 2 ), refletant les limites de l’echographie dans l’exploration de la region infundibulaire. Conclusion Ses performances autorisent l’utilisation de l’echo 3D pour surveiller les Fallot operes ; l’IRM reste indispensable pour des volumes VD de 120 a 150 ml/m 2 , ou l’indication d’une reprise chirurgicale est discutee (resection infundibulaire, revalvulation pulmonaire).

Fibroblastic endocarditis is a classic complication of prolonged hypereosinophilic syndrome, whatever the cause. In France, it is most frequently encountered in cases of idiopathic hypereosinophilic syndrome. It commonly involves the apex of the ventricles, with a clinical picture of restrictive cardiomyopathy of unfavorable prognosis, and the auriculoventricular valves. We report the case of a 77-year-old man in whom atypical cardiac involvement disclosed idiopathic hypereosinophilic syndrome. In addition to the usual features of obliteration of the apex and restrictive cardiomyopathy, echocardiographic examination showed severe left ventricular dysfunction and intracardiac tumors, one of which was unusually localized to an aortic valve. Treatment, which comprised strict control of the eosinophilic process, standard treatment for cardiac failure, and anticoagulation therapy, produced rapid and long-lasting improvement of his clinical status and left systolic and diastolic ventricular function, and on echocardiography the intracardiac tumors had totally disappeared. The patient suddenly died of septic shock 16 months after first being seen.