Jean-Marc Schleich

Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

BACKGROUND Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. METHODS In a multicenter, randomized, open‐label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long‐term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet‐only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. RESULTS A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet‐only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet‐only group (4.6% vs. 0.9%, P=0.02). The number of serious adverse events did not differ significantly between the treatment groups (P=0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. CONCLUSIONS Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation. (Funded by the French Ministry of Health; CLOSE ClinicalTrials.gov number, NCT00562289.)

Characteristics and prospective 2-year follow-up of children with pulmonary arterial hypertension in France.

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.

Characteristics and long-term outcome of non-immune isolated atrioventricular block diagnosed in utero or early childhood: a multicentre study

AIMS The natural history of congenital or childhood non-immune, isolated atrioventricular (AV) block is poorly defined. METHODS AND RESULTS We retrospectively studied 141 children with isolated, non-immune AV block diagnosed in utero, or up to 15 years of age, at 13 French medical centres, between 1980 and 2009. Patients with structural heart disease or maternal antibodies were excluded. Atrioventricular block was asymptomatic in 119 (84.4%) and complete in 100 (70.9%) patients. There was progression to complete AV block in 29/41 (70.7%) patients with incomplete AV block over 2.8 ± 3.4 years (1-155 months), but all patients with incomplete AV block may not have been included in the study. Narrow QRS complex was present in 18 of 26 patients (69.2%) with congenital, and 106 of 115 (92.2%) with childhood AV block. Pacemakers were implanted in 112 children (79.4%), during the first year of life in 18 (16.1%) and before 10 years of age in 90 (80.4%). The mean interval between diagnosis of AV block and pacemaker implants was 2.6 ± 3.9 years (0-300 months). The pacing indication was prophylactic in 70 children (62.5%). During a mean follow-up of 11.6 ± 6.7 years (1-32 years), no patient died or developed dilated cardiomyopathy (DCM). The long-term follow-up was uncomplicated in 127 children (90.1%). CONCLUSION In this large multicentre study, the long-term outcome of congenital or childhood non-immune, isolated AV block was favourable, regardless of the patients age at the time of diagnosis. No patient died or developed DCM, and pacemaker-related complications were few.

Parental Electrocardiographic Screening Identifies a High Degree of Inheritance for Congenital and Childhood Nonimmune Isolated Atrioventricular Block

Background— The origin of congenital or childhood nonimmune isolated atrioventricular (AV) block remains unknown. We hypothesized that this conduction abnormality in the young may be a heritable disease. Methods and Results— A multicenter retrospective study (13 French referral centers, from 1980–2009) included 141 children with AV block diagnosed in utero, at birth, or before 15 years of age without structural heart abnormalities and without maternal antibodies. Parents and matched control subjects were investigated for family history and for ECG screening. In parents, a family history of sudden death or progressive cardiac conduction defect was found in 1.4% and 11.1%, respectively. Screening ECGs from 130 parents (mean age 42.0±6.8 years, 57 couples) were compared with those of 130 matched healthy control subjects. All parents were asymptomatic and in sinus rhythm, except for 1 with undetected complete AV block. Conduction abnormalities were more frequent in parents than in control subjects, found in 50.8% versus 4.6%, respectively (P<0.001). A long PR interval was found in 18.5% of the parents but never in control subjects (P<0.0001). Complete or incomplete right bundle-branch block was observed in 39.2% of the parents and 1.5% of the control subjects (P<0.0001). Complete or incomplete left bundle-branch block was found in 15.4% of the parents and 3.1% of the control subjects (P<0.0006). Estimated heritability for isolated conduction disturbances was 91% (95% confidence interval, 80%–100%). SCN5A mutation screening identified 2 mutations in 2 patients among 97 children. Conclusions— ECG screening in parents of children affected by idiopathic AV block revealed a high prevalence of conduction abnormalities. These results support the hypothesis of an inheritable trait in congenital and childhood nonimmune isolated AV block.

A new dynamic 3D virtual methodology for teaching the mechanics of atrial septation as seen in the human heart

Learning embryology remains difficult, since it requires understanding of many complex phenomena. The temporal evolution of developmental events has classically been illustrated using cartoons, which create difficulty in linking spatial and temporal aspects, such correlation being the keystone of descriptive embryology. We synthesized the bibliographic data from recent studies of atrial septal development. On the basis of this synthesis, consensus on the stages of atrial septation as seen in the human heart has been reached by a group of experts in cardiac embryology and pediatric cardiology. This has permitted the preparation of three‐dimensional (3D) computer graphic objects for the anatomical components involved in the different stages of normal human atrial septation. We have provided a virtual guide to the process of normal atrial septation, the animation providing an appreciation of the temporal and morphologic events necessary to separate the systemic and pulmonary venous returns. We have shown that our animations of normal human atrial septation increase significantly the teaching of the complex developmental processes involved, and provide a new dynamic for the process of learning. Anat Sci Ed 2:69–77, 2009.

Long-term efficacy of two vena cava filter implants for congenital duplicated inferior vena cava.

MOTS CLÉS Filtres cave ; Veine cave In June 1984, a 61-year-old man presented with pulmonary embolism (PE) in the right lower lobe artery complicating left popliteal deep vein thrombosis. Oral anticoagulants were started. Four months later, the patient complained again of dyspnoea. A lung scan revealed multiple perfusion defects in the left lung suggesting a high probability of PE. No underlying conditions predisposing to thrombus formation were discovered. Since anticoagulation levels had remained within the therapeutic range, placement of an inferior vena cava (IVC) filter was advised. Venography revealed a right IVC in the normal position and an additional left IVC. The latter originated from the left common iliac vein and ended at the left renal vein, which crossed anteriorly to the aorta joining the right IVC to form a single suprarenal IVC. Two Greenfield filters were inserted percutaneously via the femoral vein into both IVCs. When inférieure ; Embolie pulmonaire last seen in March 2008, 24 years after the procedure, the patient was still receiving anticoagulant treatment and had remained free of recurrent clinical thromboembolic events. Fluoroscopy revealed that the two filters were still oriented in parallel directions (Fig. 1). Doppler ultrasound confirmed the absence of migration, tilting or occlusion of the filters (Fig. 2).

Antenatal presentation of congenital long QT syndrome: A prenatal diagnosis not to be missed.

We focus attention on the antenatal diagnosis of long QT syndrome (LQTS). Recent data show that a diagnosis of LQTS is possible at an early stage of life, namely, the fetal period, and that LQTS, now well established as capable of explaining some sudden infant death syndromes (SIDS), can explain some fetal loss [2, 8]. This new medical perspective implies strong preventative implications. Long QT syndrome is an heterogeneous inherited arrhythmia. To date, 10 responsible genes have been identified [7, 9]. The genetic prevalence is 1 to 2,000, but considering that most mutation carriers remain asymptomatic, clinical prevalence is less important [9]. Because LQTS is characterized by an abnormal prolongation of QT interval on electrocardiogram, it poses an increased risk of sudden death, usually due to ventricular fibrillation [9]. Echocardiography shows no heart structural abnormality [7, 9], and 25% of unexpected fetal loss cases remain unexplained after autopsy [6]. According to recent reports, LQTS can be diagnosed in utero. An M-mode echocardiogram or magnetocardiography, if available, can reveal sustained fetal bradycardia, decreased heart rate variability, 2:1 atrioventricular block, and ventricular arrhythmias [3–5, 10]. Fetal bradycardia is defined as a heart rate slower than 100 beats/min [4]. Recently, waveforms of torsade de pointes recorded on fetal magnetocardiogram at 28 weeks of gestation have been reported [6]. Parallel to these new fetal rhythm investigation methods, LQTS appears to be a silent killer among fetuses and newborns [8, 13]. An abnormal QT prolongation is associated with SIDS [11]. According to recent molecular screening studies, LQTS could be a strong contributor to SIDS, being responsible for 9.5% of them [1]. These findings suggest that abnormality in fetal rhythm compatible with LQTS (i.e., sustained fetal bradycardia, 2:1 atrioventricular block, or ventricular arrhythmias), even if there is no family history of sudden death, must require careful evaluation because of the risk for fetal loss, SIDS, or life-threatening events later in life. When LQTS is evoked, pregnancy should be managed in a medical center with cardiac facilities to allow preventive care such as beta-adrenergic blockers, adapted multidisciplinary follow-up assessment, identification of previously undiagnosed relatives, and early parental education with infant cardiopulmonary resuscitation and contraindicated medications. Beta-blocking therapy is known to be effective for children with LQTS [12], and some authors have reported prenatal treatment of fetal LQTS with beta-adrenergic blockers [3]. Further studies are needed to determine whether prenatal administration of this medication can be recommended.

Acquired Left Ventricular Submitral Aneurysms in the Course of Takayasu Arteritis in a Child

A 9-year-old black African boy was hospitalized for heart failure revealing a severe left ventricular dysfunction associated with dilated cardiomyopathy, two submitral aneurysms, occlusion of the circumflex artery and a giant coronary artery aneurysm on the proximal left anterior descending artery. The boy was coinfected with human immunodeficiency virus and Mycobacterium tuberculosis. Though rare, association of Takayasu arteritis and submitral aneurysm leads to rethinking the pathogenesis of submitral aneurysm and suggests that some of them may be acquired. In our case, a common inflammatory process, possibly triggered by tuberculosis or HIV, may underlie Takayasu and submitral aneurysms.

The French registry of pulmonary arterial hypertension in children: rationale and design

ABSTRACT 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 where congenital heart diseases are the cause of PAH. Conclusion: The objectives of the study are to determine the prevalence and incidence of PAH in children and to describe the characteristics, the survival in the current era and the management of paediatric PAH, paying special attention to the quality of life and impact of PAH on social and schooling activities. Recruitment for the transversal phase started in May 2005, in 21 cardiopaediatric centres that represent the majority of large University Hospitals in France, with a widespread geographical distribution. This registry will provide crucial information on PAH in children in the era of PAH-targeted therapies. It may help in identifying areas of improvement for optimal support to patients.

Understanding normal cardiac development using animated models

Learning how the human heart develops is essential in cardiology education. It lets us understand a normal hearts morphology and also explains the formation of congenital heart defects. However, learning cardiac embryology is difficult because the processes underlying the heart formation are complex. This complexity is caused by the fact that complicated organs like the heart are generated from only a couple of cells. The overall objective of the project presented was to design and develop a 3D model capable of rendering the dynamics of the various stages of normal heart development, beginning at fertilization until its final form.