NEXN Gene in Cardiomyopathies and Sudden Cardiac Deaths: Prevalence, Phenotypic Expression, and Prognosis.

BACKGROUND: Few clinical data are available on NEXN mutation carriers, and the gene's involvement in cardiomyopathies or sudden death has not been fully established. Our objectives were to assess the prevalence of putative pathogenic variants in NEXN and to describe the phenotype and prognosis of patients carrying the variants. METHODS: DNA samples from consecutive patients with cardiomyopathy or sudden cardiac death/sudden infant death syndrome/idiopathic ventricular fibrillation were sequenced with a custom panel of genes. Index cases carrying at least one putative pathogenic variant in the NEXN gene were selected. RESULTS: Of the 9516 index patients sequenced, 31 were carriers of a putative pathogenic variant in NEXN only, including 2 with double variants and 29 with a single variant. Of the 29 unrelated probands with a single variant (16 males; median age at diagnosis, 32.0 [26.0-49.0] years), 21 presented with dilated cardiomyopathy (prevalence, 0.33%), and 3 presented with hypertrophic cardiomyopathy (prevalence, 0.14%). Three patients had idiopathic ventricular fibrillation, and there were 2 cases of sudden infant death syndrome (prevalence, 0.46%). For patients with dilated cardiomyopathy, the median left ventricle ejection fraction was 37.5% (26.25-50.0) at diagnosis and improved with treatment in 13 (61.9%). Over a median follow-up period of 6.0 years, we recorded 3 severe arrhythmic events and 2 severe hemodynamic events. CONCLUSIONS: Putative pathogenic NEXN variants were mainly associated with dilated cardiomyopathy; in these individuals, the prognosis appeared to be relatively good. However, severe and early onset phenotypes were also observed-especially in patients with double NEXN variants. We also detected NEXN variants in patients with hypertrophic cardiomyopathy and sudden infant death syndrome/idiopathic ventricular fibrillation, although a causal link could not be established.

Infant congenital heart disease prevalence and mortality in French Guiana: a population-based study.

Background: Few studies have assessed the prevalence and mortality of simple or complex congenital heart diseases (CHD) in newborns. In Latin America and Caribbean (LAC), CHD epidemiology seems highly variable, with few population-based assessments and different methodologies between studies. To date, the situation in French Guiana, a French overseas territory located in South America between Brazil and Suriname, has never been described. Methods: We analysed CHD prevalence, characteristics and related infant mortality in French Guiana, with a population-based registry analysis of all fetal and live birth CHD cases in infants under 1 year (January 2012-December 2016). Findings: Overall, 33,796 births (32,975 live births) were registered, with 231 CHD (56 fetuses), including 215 live births. Most frequent CHD categories were anomalies of the ventricular outflow tract and extra-pericardial trunks, and ventricular septal defects. 18.6% (43/231) chromosomal or genetic anomalies, and 6.5% (15/231) terminations of pregnancy were observed. Total CHD prevalence was 68.4 [95% CI: 67.9-68.8] per 10,000, while live birth prevalence was 65.2 [95% CI: 64.7-65.7] per 10,000. Total infant mortality was 9.4/10,000 live births [95% CI 9.1-9.7], with highest rates for functionally univentricular hearts (FUH). Interpretation: A distinct profile for CHD is highlighted in French Guiana with elevated mortality linked to FUH. A potential determinant of the recognized excess mortality risk might be the presence of chromosomal or genetic anomalies in about a fifth of all CHD. This helps us to better understand CHD burden in this part of South America and provides future keys towards reducing CHD-related infant mortality. Funding: The authors received no financial support for the present research, authorship, and/or publication of this article.

Giant Localized Atheroma Mimicking a Coarctation of the Aorta: A Rare Entity to Consider.

We describe the case of a patient who developed resistant hypertension due to a giant atheroma with acquired physiologic mimic of coarctation of the aorta. This presentation illustrates an extremely rare etiology to consider in adults in whom aortic isthmus stenosis remains often of congenital origin. (Level of Difficulty: Intermediate.).

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

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

Patent foramen ovale closure in children without cardiopathy: Child-PFO study.

BACKGROUND: Closure of patent foramen ovale is well-managed in adults, but is performed less frequently in children. AIM: To analyse all patent foramen ovale closures performed in the past 20 years in French paediatric centres. METHODS: Retrospective study of patent foramen ovale closures in children without cardiopathy in nine centres between 2000 and 2019. RESULTS: Forty-one procedures were carried out in children (median age: 14.9 years). Thirty-one patent foramen ovales were closed after a transient ischaemic attack or stroke, six for a left-to-right shunt and four for other reasons. Transthoracic echocardiography was used for 72.2% of the diagnoses and transoesophageal echocardiography for 27.8%. A substantial degree of shunting was found in 42.9% of patients and an atrial septal aneurysm in 56.2%. General anaesthesia with transoesophageal echocardiography guidance was performed in 68.3% of the procedures; local anaesthesia and transthoracic echocardiography or intracardiac echocardiography was performed in 31.7%. The success rate was 100%. The median fluoroscopy time was 4.14minutes: 3.55minutes with transoesophageal echocardiography; and 4.38minutes with transthoracic echocardiography (P=0.67). There was only one periprocedural complication (2.4%). Postoperatively, 80,5% of patients were treated with aspirin and 12,2% with an anticoagulant. The rate of complete occlusion was 56.8% immediately after the procedure, 68.6% at 1 year and 92.3% at the last follow-up. There were no delayed complications or cases of recurrent stroke during follow-up (median follow-up: 568 days). CONCLUSION: Closure of patent foramen ovale in children appears to be safe and effective, as we noted a low rate of immediate complications, no delayed complications and no stroke recurrence in this indication.

Is the new Occlutech duct occluder an appropriate device for transcatheter closure of patent ductus arteriosus?

AIM: To describe our initial experience with the Occlutech Duct Occluder (ODO) for percutaneous closure of patent ductus arteriosus (PDA). METHODS: Retrospective review of patients undergoing transcatheter PDA closure with the ODO in 2 academic centers. RESULTS: From April 2013 to September 2017, 42 patients underwent PDA closure. Median age at implantation was 34 months (range 4 months-68 years) and median weight was 12 kg (range 4.1-57 kg). Ducts were Krichenko type A duct (n = 34), type E (n = 6), and type C (n = 2). The mean duct diameter was 3.76 mm (range 1.69 to 9.95 mm, median 3.1 mm). Implantation succeeded in all. There was neither device embolization nor hemolysis. At device release, immediate angiogram showed a small residual shunt in 54.7%. During follow-up, Doppler echocardiography demonstrated 71% of full occlusion at day one, rising to 95% at one month and 100% at one year and half after implantation. The mean maximal systolic pressure gradient in left pulmonary artery was 4.2 ±â€¯4.3 mm and across the distal aortic arch 5.4 ±â€¯4.7 mm Hg. No patient had any significant stenosis with clinical relevance. CONCLUSIONS: ODO is safe and effective in transcatheter closure of PDA including relatively large sized ducts. The results are satisfactory with a high level of full occlusion and a low rate of complications. Further evaluation with larger studies and longer follow-up will be required to confirm these preliminary good results.

Isolated severe leftward displacement of the septum primum: anatomic and 3D echocardiographic findings and surgical repair.

OBJECTIVES: Leftward displacement of the septum primum is usually described as associated with hypoplastic left heart syndrome or visceral heterotaxy. This rare malformation results in partially or totally anomalous pulmonary venous drainage with a normal connection of the pulmonary veins to the left atrium, depending on the degree of septal shift. We report the 3D echocardiographic and anatomic findings as well as the surgical repair in a series of isolated severe leftward displacement of the septum primum, responsible for totally anomalous pulmonary venous drainage. METHODS: Three patients presenting with situs solitus and extreme leftward displacement of the septum primum were included. All of the pulmonary veins drained anomalously into the anatomical right atrium, and the distance between the mitral valve and the abnormal septum primum was greatly reduced, compromising the size of the left atrial chamber, but with normal left ventricle diameters. Preoperative 3D echocardiographic findings are reported. We achieved a biventricular surgical repair in all cases. The atrial septation was accomplished using an autologous pericardial patch after removing the abnormal septal membrane. RESULTS: The postoperative course was free from any cardiovascular complications. Echocardiographic scans showed a harmonious reconstruction without pulmonary venous obstructions or stenosis. CONCLUSIONS: This article reports the severe leftward displacement of the septum primum presented as an isolated cardiac malformation; 3D transthoracic echocardiography allowed an accurate diagnosis of this malformation and helped in choosing the best surgical strategy.

Nontoxinogenic corynebacterium diphtheriae as a rare cause of native endocarditis in childhood.

We report a pediatric case of negative blood culture pulmonary valve endocarditis caused by a nontoxinogenic Corynebacterium diphtheriae biotype gravis and review the literature on this disease.

Acute ischemic cardiomyopathy after extreme emotional stress in a child.

Ischemic cardiomyopathy is rare in children. It is usually caused by congenital anomalies of coronary arteries, coronary anomalies after coronary artery transfer, or Kawasaki disease. In recent years, a new cardiac syndrome-named "Tako-Tsubo cardiomyopathy" for the particular shape of the end systolic ventricle-has been described in adults. In the absence of coronary artery obstruction, it mimics acute myocardial infarction with chest pain and typical electrocardiography changes. Emotional or physical stress usually precedes this cardiomyopathy. At present, this entity has only been described in adults, with a strong predominance in postmenopausal women. We report a case of acute ischemic cardiomyopathy after extreme stress in a child that may share the same pathophysiology.

Value of programmed ventricular stimulation after tetralogy of fallot repair: a multicenter study.

BACKGROUND: Studies have consistently shown that ventricular tachycardia (VT) and sudden cardiac death (SCD) complicate the long-term outcome after tetralogy of Fallot repair, yet the diagnostic and predictive value of electrophysiological testing in this population is uncertain. METHODS AND RESULTS: A multicenter cohort of 252 patients with repaired tetralogy of Fallot undergoing programmed ventricular stimulation was followed up for 18.5+/-9.6 and 6.5+/-4.5 years after corrective surgery and electrophysiological testing, respectively. Clinical VT and/or SCD occurred in 24.6%. Sustained monomorphic VT and polymorphic VT were induced in 30.2% and 4.4%. Including polymorphic VT in the definition of inducibility improved sensitivity (66.1+/-6.0% versus 77.4+/-5.3%, P=0.0082) with a marginal reduction in specificity (81.6+/-2.8% versus 79.5+/-2.9%, P=0.0455). Positive and negative predictive values were 55.2+/-5.3% and 91.5+/-2.2%. Independent risk factors for inducibility were age at study > or =18 years (OR, 3.3), palpitations (OR, 2.8), prior palliative surgery (OR, 3.1), modified Lown criteria > or =2 (OR, 5.6), and cardiothoracic ratio > or =0.6 (OR, 3.3). Event-free survival rates in noninducible and inducible patients at 1, 5, 10, and 15 years were 97.9%, 92.8%, 89.3%, and 89.3% versus 79.4%, 62.6%, 58.7%, and 50.3%, respectively (P<0.0001). Both inducible monomorphic VT [relative risk (RR), 5.0; P=0.0002] and polymorphic VT (RR, 12.9; P<0.0001) predicted future clinical VT and SCD. In a multivariate analysis, inducible sustained VT was an independent risk factor for subsequent events (RR, 4.7; 95% CI, 1.2 to 18.5; P=0.0268). CONCLUSIONS: Programmed ventricular stimulation is of diagnostic and prognostic value in risk stratifying patients with repaired tetralogy of Fallot. In this patient population, inducible sustained polymorphic VT should not be disregarded as nonspecific.

Evidence of early impairments in both right and left ventricular inotropic reserves in children with Duchenne's muscular dystrophy.

In Duchenne's muscular dystrophy (DMD), cardiac function deteriorates with time and heart failure is one of the major causes of death. The aim of the study was to determine if a decrease in the ventricular inotropic reserves could be an early sign of cardiac dysfunction in these children. Nineteen children with DMD (aged 9 to 18 years, mean age 13.6 +/- 2.4) underwent equilibrium radionuclide angiography at rest and during an inotropic stimulation with low-dose dobutamine perfusion (7.5 to 15 microg. kg(-1). min(-1)). In all patients, this investigation was short (<30 minutes), successful, and uncomplicated. At rest, left ventricular (LV) ejection fraction (EF) was normal (>0.50) in 79% of patients, and right ventricular (RV) EF was normal (>0.45) in 95%. There was a trend toward a decrease with age for rest LVEF (p = 0.051) but not for rest RVEF (p = 0.8). By contrast, marked declines with age could be documented for the increases (Delta) in LVEF and RVEF during dobutamine perfusion (p = 0.002 for DeltaLVEF and p = 0.015 for DeltaRVEF). Thus, by multivariate analysis, the sole best indicator of decline in cardiac function with age was LVEF determined with dobutamine. In children with DMD, low-dose dobutamine radionuclide angiography gives evidence of an early decline with age of the inotropic reserves of both ventricles.