Transcatheter tricuspid valve implantation: A multicentre French study

SummaryBackgroundTranscatheter valve-in-valve (VIV) implantation in failing bioprosthesis is an emerging field in cardiology.AimTo report on a French multicentre experience and a literature review of tricuspid VIV implantation.MethodsWe approached different institutions and collected 10 unpublished cases; a literature review identified 71 patients, including our 10 cases. Clinical aspects and haemodynamic data are discussed.ResultsAmong our 10 unpublished cases, the reason for implantation was significant tricuspid stenosis (n=4), significant tricuspid regurgitation (n=1) or mixed lesion (n=5). Implantation was performed under general anaesthesia at mean age 28±17 years. The 22mm Melody valve was implanted in seven patients; the Edwards SAPIEN valve was implanted in three patients. The procedure succeeded in all cases, despite two embolizations in the right cardiac chambers; in both cases, the valve was stabilized close to the tricuspid annulus using a self-expandable stent, before implantation of a second Edwards SAPIEN valve. Functional class improved in all but one case. Mean diastolic gradient decreased from 9±2.45mmHg to 3.65±0.7mmHg (p=0.007); no more than trivial regurgitation was noticed. Among the published cases, the Melody valve was implanted in 41 patients, the Edwards SAPIEN valve in 29 patients and the Braile valve in one patient. Short-term results were similar for our 10 cases, but mid-term results are not yet available.ConclusionsTricuspid VIV implantation using the Melody or Edwards SAPIEN valves is a feasible and effective procedure for selected patients with failing bioprosthesis

Diagnostic Value of (18)F-Fluorodeoxyglucose Positron Emission Tomography Computed Tomography in Prosthetic Pulmonary Valve Infective Endocarditis

OBJECTIVES: The aim of this study was to assess the diagnostic performances of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) in congenital heart disease (CHD) patients with pulmonary prosthetic valve or conduit endocarditis (PPVE) suspicion. BACKGROUND: PPVE is a major issue in the growing CHD population. Diagnosis is challenging, and usual imaging tools are not always efficient or validated in this specific population. Particularly, the diagnostic yield of (18)F-FDG PET/CT remains poorly studied in PPVE. METHODS: A retrospective multicenter study was conducted in 8 French tertiary centers. Children and adult CHD patients who underwent (18)F-FDG PET/CT in the setting of PPVE suspicion between January 2010 and May 2020 were included. The cases were initially classified as definite, possible, or rejected PPVE regarding the modified Duke criteria and finally by the Endocarditis Team consensus. The result of (18)F-FDG PET/CT had been compared with final diagnosis consensus used as gold-standard in our study. RESULTS: A total of 66 cases of PPVE suspicion involving 59 patients (median age 23 years, 73% men) were included. Sensitivity, specificity, positive predictive value, and negative predictive value of (18)F-FDG PET/CT in PPVE suspicion were respectively: 79.1% (95% CI: 68.4%-91.4%), 72.7% (95% CI: 60.4%-85.0%), 91.9% (95% CI: 79.6%-100.0%), and 47.1% (95% CI: 34.8%-59.4%). (18)F-FDG PET/CT findings would help to correctly reclassify 57% (4 of 7) of possible PPVE to definite PPVE. CONCLUSIONS: Using (18)F-FDG PET/CT improves the diagnostic accuracy of the Duke criteria in CHD patients with suspected PPVE. Its high positive predictive value could be helpful in routine to shorten diagnosis and treatment delays and improve clinical outcomes.L'Institut de Rythmologie et modélisation Cardiaqu

Noncardiac genetic predisposition in sudden infant death syndrome.

PURPOSE: Sudden infant death syndrome (SIDS) is the commonest cause of sudden death of an infant; however, the genetic basis remains poorly understood. We aimed to identify noncardiac genes underpinning SIDS and determine their prevalence compared with ethnically matched controls. METHODS: Using exome sequencing we assessed the yield of ultrarare nonsynonymous variants (minor allele frequency [MAF] ≤0.00005, dominant model; MAF ≤0.01, recessive model) in 278 European SIDS cases (62% male; average age =2.7 ± 2 months) versus 973 European controls across 61 noncardiac SIDS-susceptibility genes. The variants were classified according to American College of Medical Genetics and Genomics criteria. Case-control, gene-collapsing analysis was performed in eight candidate biological pathways previously implicated in SIDS pathogenesis. RESULTS: Overall 43/278 SIDS cases harbored an ultrarare single-nucleotide variant compared with 114/973 controls (15.5 vs. 11.7%, p=0.10). Only 2/61 noncardiac genes were significantly overrepresented in cases compared with controls (ECE1, 3/278 [1%] vs. 1/973 [0.1%] p=0.036; SLC6A4, 2/278 [0.7%] vs. 1/973 [0.1%] p=0.049). There was no difference in yield of pathogenic or likely pathogenic variants between cases and controls (1/278 [0.36%] vs. 4/973 [0.41%]; p=1.0). Gene-collapsing analysis did not identify any specific biological pathways to be significantly associated with SIDS. CONCLUSIONS: A monogenic basis for SIDS amongst the previously implicated noncardiac genes and their encoded biological pathways is negligible

Congenital and childhood atrioventricular blocks: pathophysiology and contemporary management

Atrioventricular block is classified as congeni- tal if diagnosed in utero, at birth, or within the first month of life. The pathophysiological process is believed to be due to immune-mediated injury of the conduction system, which occurs as a result of transplacental pas- sage of maternal anti-SSA/Ro-SSB/La antibodies. Childhood atrioventricular block is therefore diagnosed between the first month and the 18th year of life. Genetic variants in multiple genes have been described to date in the pathogenesis of inherited progressive car- diac conduction disorders. Indications and techniques of cardiac pacing have also evolved to allow safe perma- nent cardiac pacing in almost all patients, including those with structural heart abnormalities

SCN5A mutations in 442 neonates and children: genotype-phenotype correlation and identification of higher-risk subgroups.

Aims To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification. Methods and results A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation were included in the analysis. There was no restriction made based on their clinical diagnosis. A total of 442 children {55.7% boys, 40.3% probands, median age: 8.0 [interquartile range (IQR) 9.5] years} from 350 families were included; 67.9% were asymptomatic at diagnosis. Four main phenotypes were identified: isolated progressive cardiac conduction disorders (25.6%), overlap phenotype (15.6%), isolated long QT syndrome type 3 (10.6%), and isolated Brugada syndrome type 1 (1.8%); 44.3% had a negative electrocardiogram phenotype. During a median follow-up of 5.9 (IQR 5.9) years, 272 cardiac events (CEs) occurred in 139 (31.5%) patients. Patients whose mutation localized in the C-terminus had a lower risk. Compound genotype, both gain- and loss-of-function SCN5A mutation, age ≤1 year at diagnosis in probands and age ≤1 year at diagnosis in non-probands were independent predictors of CE. Conclusion In this large paediatric cohort of SCN5A mutation-positive subjects, cardiac conduction disorders were the most prevalent phenotype; CEs occurred in about one-third of genotype-positive children, and several independent risk factors were identified, including age ≤1 year at diagnosis, compound mutation, and mutation with both gain- and loss-of-function

The differential diagnosis of primary electrical diseases from seizures in childhood.

Published in "Cardiology in the Young" vol.20, n°1Letter to the edito

Inherited progressive cardiac conduction disorders

International audiencePURPOSE OF REVIEW: Progressive cardiac conduction disorder (PCCD) is an inherited cardiac disease that may present as a primary electrical disease or be associated with structural heart disease. In this brief review, we present recent clinical, genetic, and molecular findings relating to PCCD. RECENT FINDINGS: Inherited PCCD in structurally normal hearts has been found to be linked to genetic variants in the ion channel genes SCN5A, SCN1B, SCN10A, TRPM4, and KCNK17, as well as in genes coding for cardiac connexin proteins. In addition, several SCN5A mutations lead to 'cardiac sodium channelopathy overlap syndrome'. Other genes coding for cardiac transcription factors, such as NKX2.5 and TBX5, are involved in the development of the cardiac conduction system and in the morphogenesis of the heart. Mutations in these two genes have been shown to cause cardiac conduction disorders associated with various congenital heart defects. SUMMARY: PCCD is a hereditary syndrome, and genetic variants in multiple genes have been described to date. Genetic screening and identification of the causal mutation are crucial for risk stratification and family counselling