Severe Antenatal Hypertrophic Cardiomyopathy Secondary to ACAD9-Related Mitochondrial Complex I Deficiency.

Introduction: Antenatal presentation of hypertrophic cardiomyopathy (HCM) is rare. We describe familial recurrence of antenatal HCM associated with intrauterine growth restriction and the diagnostic process undertaken. Methods: Two pregnancies with antenatal HCM were followed up. Biological assessment including metabolic analyses, genetic analyses, and respiratory chain study was performed. We describe the clinical course of these two pregnancies, antenatal manifestations as well as specific histopathological findings, and review the literature. Results: The assessment revealed a deficiency in complex I of the respiratory chain and two likely pathogenic variations in the ACAD9 gene. Discussion and Conclusion: Antenatal HCM is rare and a diagnosis is not always made. In pregnancies presenting with cardiomyopathy and intrauterine growth restriction, ACAD9 deficiency should be considered as one of the potential underlying diagnoses, and ACAD9 molecular testing should be included among other prenatal investigations.

Transcatheter closure of a perimembranous ventricular septal defect with Nit-Occlud Lê VSD Coil: A French multicentre study.

BACKGROUND: Transcatheter perimembranous ventricular septal defect (pmVSD) closure remains challenging and is seldom used in France given the risk of atrioventricular block (AVB). pmVSD closure with the Nit-Occlud Lê VSD coil was recently introduced in France as an alternative to occluder devices. AIMS: To study the safety and feasibility of pmVSD closure with the Nit-Occlud Lê VSD coil. METHODS: All consecutives cases of pmVSD closure with the Nit-Occlud Lê VSD coil in 20 tertiary French centres were included between January 2015 and December 2018. RESULTS: Among 46 procedures in five centres, indications for pmVSD closure were left ventricle overload (76.1%), exertional dyspnoea (17.4%), history of infective endocarditis (4.3%) and mild pulmonary hypertension (2.2%). The median (interquartile [IQR]) age of the patients was 13.9 (5.7-31.8) years. Aneurismal tissue was identified in 91.3% of patients. VSD median (IQR) size was 8 (7-10) mm on the left ventricle side and 5 (4-6) mm on the right ventricle side. Implantation was successful in 40 patients (87.0%; 95% confidence interval [CI] 73.7-95.1%). Severe complications occurred in six patients (13.0%, 95% CI 4.9-26.3%), mainly severe haemolysis (8.7%, 95% CI 2.4-20.8%). One aortic valve lesion required surgical aortic valvuloplasty. Occurrence of severe complications was significantly related to the presence of haemolysis (P=0.001), residual shunt (P=0.007) and multi-exit VSD (P=0.005). Residual shunt was observed in 40% of cases with the implanted device shortly after closure and 15% after a median follow-up of 27 months. No immediate or delayed device embolization or complete AVB was recorded. CONCLUSION: pmVSD closure with the Nit-Occlud Lê VSD Coil is feasible in older children and adults. However, residual shunting (leading to haemolysis) is a dreaded complication that should not be tolerated. pmVSD closure with the Nit-Occlud Lê VSD as a therapeutic strategy remains controversial and is limited to selected patients.

Feasibility, Safety and Accuracy of Echocardiography-Fluoroscopy Imaging Fusion During Percutaneous Atrial Septal Defect Closure in Children.

BACKGROUND: Imaging fusion between echocardiography and fluoroscopy was recently developed. The aim of this study was to assess its feasibility and accuracy during pediatric cardiac catheterization. METHODS: Thirty-one patients (median weight, 26 kg; interquartile range [IQR], 21-37 kg) who underwent percutaneous atrial septal defect closure were prospectively included. The feasibility and accuracy of various imaging fusion modalities (live two-dimensional, live color two-dimensional, live three-dimensional and markers) with EchoNavigator software were assessed. To assess the accuracy of spatial registration of the echocardiogram on the fluoroscopic image, the occluder screw, an object that appeared on each image, was used as a reference tool, and the distance between the two when fused was measured. A distance was measured on the fusion screen between a marker positioned on the screw from the echocardiography screen and from the fluoroscopy screen (distance 1). Another distance was measured on the fusion screen between the screw visualized by three-dimensional echocardiography and by fluoroscopy (distance 2). The two distances were measured on four C-arm orientations in end-systolic and end-diastolic frames. RESULTS: Fusion and marker positioning were feasible in real time in all cases. On the fusion screen, median systolic and diastolic distance 1 were 0.5 mm (IQR, 0.3-1 mm) and 2 mm (IQR, 1.5-2.5 mm; P < .0001), respectively. The marker positioned from the echocardiography screen was fixed on the fusion screen and did not follow the movement of the screw. Median systolic and diastolic distance 2 were 0.5 mm (IQR, 0-0.5 mm) and 2 mm (IQR, 1.5-2.5 mm; P < .0001), respectively. CONCLUSIONS: Echocardiographic fluoroscopic imaging fusion is feasible, safe, and accurate in children weighting >20 kg. This technique offers a new method of imaging guidance in the catheterization laboratory for complex procedures and training.

French national survey on infective endocarditis and the Melody™ valve in percutaneous pulmonary valve implantation.

BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) is a routine treatment for dysfunctional right ventricular outflow tract. Infective endocarditis (IE) is a major concern. AIM: To report French experience with the Melody™ valve (Medtronic Inc., Minneapolis, MN, USA). METHODS: All patients who underwent PPVI were recorded in a multicentre French national survey. Demographic and procedural data were collected from patients with IE. Bacterial identification, diagnostic tools and outcome were recorded. RESULTS: Forty-five cases of IE were diagnosed in 43 patients. The cumulative IE incidence was 11.8% (95% confidence interval [CI] 8.5-15.9). The annualized IE incidence was 3.6% (95% CI 0-4.8). Freedom from IE was 96.3% and 85.8% at 12 months and 60 months, respectively. IE incidence did not change during the study period. The mean interval between PPVI and IE was 2.6±2.1 years (range, 5 days to 7.3 years). Fifteen patients with IE required intravenous antibiotics only. Seven patients had early interventional cardiac catheterization to relieve severe right ventricular outflow tract obstruction. Twenty-four patients had surgical valve replacement (six urgently; nine semi-urgently; nine electively). Staphylococcus aureus IE required surgery in all but one patient. Three patients died before any treatment. Three additional patients died, giving a mortality rate of 14%. Global survival in the total cohort of patients who received a Melody valve was excellent (96.5% at 5 years). When comparing survival curves between the IE and non-IE groups, death and cardiovascular events were statistically significantly higher in the IE group (log-rank P<0.0001). CONCLUSION: Melody valve IE is a severe complication following PPVI. The annualized IE incidence in this cohort was similar to rates reported in other studies. With rapid diagnosis and adequate treatment, outcome has improved, and unfavourable outcome is mainly associated with S. aureus.

Ablation of supraventricular arrhythmias in adult congenital heart disease: A contemporary review.

Supraventricular arrhythmias are an important and increasing cause of morbidity in adults with congenital heart disease, requiring specific management strategies. Pharmacological treatment has limited efficacy, and is often associated with some side-effects. Major improvements in catheter ablation techniques have opened new opportunities to better understand underlying mechanisms of supraventricular arrhythmias, offer better therapy, and eventually improve symptoms and quality of life in these patients. An array of tools and techniques are necessary to access relevant anatomical areas to address the arrhythmogenic substrate. The mechanism of these arrhythmias is mostly related to macroreentry around surgical scars or cavotricuspid isthmus-dependent flutter. The efficacy of catheter ablation is mainly dependent on the underlying congenital heart condition, with the most complex cases typically being associated with atrial switch and Fontan surgeries. Although relatively high rates of recurrence are seen after a single procedure, additional attempts are often helpful to decrease recurrences and improve symptoms. Catheter ablation in such patients continues to present many unique challenges that are best addressed by experienced multidisciplinary teams, at centres equipped with the proper catheters, imaging capabilities, mapping systems and support staff needed to maximize safety and success. Consensus indications have emerged that often support ablation as first-line therapy in these patients. In this comprehensive review, we aim to describe the specific issues associated with ablation of supraventricular arrhythmias in adult congenital heart disease, assess the results in contemporary practice and, finally, review the current indications.

A systematic variant screening in familial cases of congenital heart defects demonstrates the usefulness of molecular genetics in this field.

The etiology of congenital heart defect (CHD) combines environmental and genetic factors. So far, there were studies reporting on the screening of a single gene on unselected CHD or on familial cases selected for specific CHD types. Our goal was to systematically screen a proband of familial cases of CHD on a set of genetic tests to evaluate the prevalence of disease-causing variant identification. A systematic screening of GATA4, NKX2-5, ZIC3 and Multiplex ligation-dependent probe amplification (MLPA) P311 Kit was setup on the proband of 154 families with at least two cases of non-syndromic CHD. Additionally, ELN screening was performed on families with supravalvular arterial stenosis. Twenty-two variants were found, but segregation analysis confirmed unambiguously the causality of 16 variants: GATA4 (1 ×), NKX2-5 (6 ×), ZIC3 (3 ×), MLPA (2 ×) and ELN (4 ×). Therefore, this approach was able to identify the causal variant in 10.4% of familial CHD cases. This study demonstrated the existence of a de novo variant even in familial CHD cases and the impact of CHD variants on adult cardiac condition even in the absence of CHD. This study showed that the systematic screening of genetic factors is useful in familial CHD cases with up to 10.4% elucidated cases. When successful, it drastically improved genetic counseling by discovering unaffected variant carriers who are at risk of transmitting their variant and are also exposed to develop cardiac complications during adulthood thus prompting long-term cardiac follow-up. This study provides an important baseline at dawning of the next-generation sequencing era.

The relation between atrial septal defect shape, diameter, and area using three-dimensional transoesophageal echocardiography and balloon sizing during percutaneous closure in children.

BACKGROUND: A trans-catheter closure of an atrial septal defect (ASD) is efficient. Balloon sizing (BS) during the catheterization leads to an overestimation of ASD size. Three-dimensional transoesophageal echocardiography (3D-TEE) allows the ASD morphology to be assessed comprehensively. The aim of this study was to assess the relationships between the shape and the measurements of ASDs by 2D-, 3D-TEE, and BS in children. METHODS AND RESULTS: Thirty children who underwent percutaneous closures of a single ASD were enrolled. ASD diameters were measured by 2D-transthoracic echocardiography (TTE), 2D-TEE, 3D-TEE and compared with BS. The ASD area was measured on 3D-TEE images after multi-planar reconstruction. ASD was estimated as round or oval on 3D-TEE 'en-face' view. 2D-TTE, 2D-TEE, and 3D-TEE(max) ASD diameters were well correlated with BS (r = 0.75; 0.80, and 0.85, respectively). Mean diameters were all significantly smaller than the mean BS. The mean difference between the balloon area and 3D-TEE area was 1.6 ± 1.4 cm(2) (P < 0.0001). The mean difference between BS and 3D-TEE(max) diameters was higher in round ASDs than in oval ASDs (4.0 ± 3.3 vs. 1.1 ± 3.3, P = 0.02). With multivariate linear regression analysis, two formulas were built to predict BS. The first model was BS = 1.07 × 3D-TEE(max)- 3.1 × ASDshape + 3. The ASD shape was 0 for round and 1 for oval ASDs. A second model was BS = 4.5 × ASDarea + 11.5. CONCLUSION: The ASD shape is accurately estimated by 3D-TEE and influences the relationship between echocardiographic measurements and BS. The ASD shape, its maximal diameter and the area assessed by 3D-TEE may be sufficient to determine the device size without BS in children.

Striking phenotypic variability in two familial cases of myosin storage myopathy with a MYH7 Leu1793pro mutation.

Myosin Storage Myopathies (MSM) have emerged as a new group of inherited myopathies with heterogenous clinical severity and age of onset. We have identified in a woman and her daughter, a pLeu1793Pro mutation in MYH7. This mutation has already been reported to be associated with MSM presenting as neonatal hypotony. Our index case complained of proximal muscle weakness at age 30. Her daughter presented at birth with a cardiomyopathy without any skeletal muscle involvement. This report underlines the clinical variability of MSM even with a given mutation or in a same family.