Identification and quantification of prosthetic mitral regurgitation by flow convergence method using transthoracic approach

The present case report illustrates the clinical applicability of the proximal isovelocity surface area (PISA) method in identifying, locating and assessing paravalvular prosthetic mitral regurgitation by transthoracic echocardiography

Bicuspidie aortique et dystrophie de l'aorte ascendante (analyse phénotypique et génomique par puce à ADN)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Traitement chirurgical de l'insuffisance mitrale fonctionnelle chronique (étude pronostique comparée de l'annuloplastie et du remplacement valvulaire)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Genetic and phenotypic continuum of HOXA genes: A case with double HOXA9/HOXA13 mutations

International audienceThe HOXA genes cluster plays a key role in embryologic development. Mutations in HOXA genes have been linked to different human phenotypes, including developmental delay, limb anomalies, and urogenital malformations. The present study reported a clinical and genetic investigation of a female patient with polymalformative syndrome including left arm agenesis, bicornuate uterus and bicuspid aortic valve. using whole exome sequencing, two heterozygous missense variants were identified. Of these, one was a novel variant in the HOXA13 gene [p.(Tyr290Ser)] and the second a heterozygous variant in the HOXA9 gene [p.(ala102Pro)]. To the best of our knowledge, this is the first association of HOXA9/HOXA13 point mutations linked to a syndromic case. in conclusion, the present study suggested that the phenotypic spectrum of vertebral anomalies, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies and limb abnormalities/hand-foot-genital syndrome may be attributable to the combination of different HOXA variants, particularly in patients with a severe clinical presentation. The current report contributed as well to the molecular understanding of HOXA genes-related phenotypes via the identification of novel variant and genes associations

Krox20 heterozygous mice: A model of aortic regurgitation associated with decreased expression of fibrillar collagen genes

International audienceBackground. - The mechanism involved in the onset of aortic valve (AoV) disease remains unclear despite its poor prognosis and frequency. Recently, we reported that Krox20 (EGR2 in humans) is involved in AoV development and dysfunction. Aim. - Analyze Krox20 heterozygous mice (Krox20(+/-)) to discover whether incomplete expression of Krox20 can cause valvular diseases. Methods. - Transcriptional levels of Col1a2/COL1A2 and Krox20/EGR2 in AoVs from Krox20(+/-) mice and human patients operated on for severe aortic regurgitation were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Human control valves were obtained from three transplanted patients without AoV disease. Twenty-one heterozygous Krox20(+/-) mice were compared with 35 controls at different ages. Three independent measurements of valve thickness were performed on magnified tissue sections using Image J software. In vivo valve structure and function were evaluated using the high-frequency Vevo (R) 2100 echocardiogram. Results. - qRT-PCR analysis using AoVs from patients with severe aortic regurgitation showed a decrease in EGR2 expression associated with significant downregulation of COL1A2 expression (P 7 vs. < 7 months: 136 +/- 48 vs. 102 +/- 41 mu m; P<0.001). Moreover, the aortic leaflets of embryonic day 18.5 Krox20(+/-) embryos were significantly more thickened than those from controls, suggesting that this disease begins during embryonic development. Echo-Doppler analysis showed a significant increase in AoV dysfunction in heterozygous versus control mice (53% vs. 17%; P<0.001), suggesting a tight relationship between valve architecture and function. Morphometric analysis revealed that the most severe AoV dysfunction was always associated with the most thickened valves. Classic histological analysis revealed that mutant AoVs had extracellular matrix disorganization, with features of human myxomatous degeneration, including excess of proteoglycan deposition in spongiosa and reduction of collagen fibre in fibrosa, but no calcification. Conclusion. - Decreased expression of Krox20 in mice causes degeneration of the aortic leaflets and disorganization of the extracellular matrix, causing valvular dysfunction. (C) 2015 Elsevier Masson SAS. All rights reserved

Usefulness of 3-Tesla Cardiac Magnetic Resonance to Detect Mitral Annular Disjunction in Patients With Mitral Valve Prolapse

International audienceMitral annulus disjunction (MAD) is characterized by a separation between the atrial wall mitral junction and the left ventricular (LV) free wall. Little is known regarding cardiac magnetic resonance (CMR) performance to detect MAD and its prevalence in mitral valve prolapse (MVP). Based on 89 MVP patients (63 women; mean age 64 +/- 13) referred for CMR assessment of MR, either from myxomatous mitral valve disease (MMVP) (n = 40; 45%) or fibroelastic disease (n = 49; 55%), we sought to assess the frequency of MAD and its consequences on LV morphology. Patients were classified in 2 groups according to MAD presence (MAD+) or absence (MAD-). MAD (measuring 8 +/- 4 mm) was diagnosed in 35% (31 of 89) of MVP patients, more frequently in MMVP than fibroelastic disease (60% vs 14%). MAD+ was associated with MMVP; bileafiet MVP and nonsustain ventricular tachycardia but not with the severity of MR. Diagnostic accuracy of transthoracic echocardiography for the detection of MAD was fair (65% sensitivity, 96% specificity) with CMR as reference. MAD+ showed significantly enlarged basal and mid LV diameters and enlarged mitral-annulus diameter. In patients with late gadolinium enhancement, presence of LV fibrosis at level of papillary muscle was more frequent in MAD+. After adjustment on age and MR severity, MMVP, and enlarged end-systolic mitral annulus diameter were independently associated with MAD+. In conclusion, MAD was present in about 1/3 of MVP patients, mostly in MMVP and independent of MR severity. Enlarged mitral-annulus and basal LV diameters, nonsustain ventricular tachycardia and papillary muscle fibrosis were associated with MAD presence. (C) 2019 Elsevier Inc. All rights reserved

Reduced aggrecan expression affects cardiac outflow tract development in zebrafish and is associated with bicuspid aortic valve disease in humans

International audienceAvailable online xxxx Hemodynamic forces have been known for a long time to regulate cardiogenic processes such as cardiac valve development. During embryonic development in vertebrates, the outflow tract (OFT) adjacent to the ventricle comes under increasing hemodynamic load as cardiogenesis proceeds. Consequently, extracellular matrix components are produced in this region as the cardiac cushions form which will eventually give rise to the aortic valves. The proteoglycan AGGRECAN is a key component of the aortic valves and is frequently found to be deregulated in a variety of aortic valve diseases. Here we demonstrate that aggrecan expression in the OFT of developing zebrafish embryos is hemodynamically dependent, a process presumably mediated by mechanosensitive channels. Furthermore, knockdown or knockout of aggrecan leads to failure of the OFT to develop resulting in ste-nosis. Based on these findings we analysed the expression of AGGRECAN in human bicuspid aortic valves (BAV). We found that in type 0 BAV there was a significant reduction in the expression of AGGRECAN. Our data indicate that aggrecan is required for OFT development and when its expression is reduced this is associated with BAV in humans

Identification of non-synonymous variations in ROBO1 and GATA5 genes in a family with bicuspid aortic valve disease

International audienc