Dataset Information

Effect of altered haemodynamics on the developing mitral valve in chick embryonic heart.

ABSTRACT: Intracardiac haemodynamics is crucial for normal cardiogenesis, with recent evidence showing valvulogenesis is haemodynamically dependent and inextricably linked with shear stress. Although valve anomalies have been associated with genetic mutations, often the cause is unknown. However, altered haemodynamics have been suggested as a pathogenic contributor to bicuspid aortic valve disease. Conversely, how abnormal haemodynamics impacts mitral valve development is still poorly understood. In order to analyse altered blood flow, the outflow tract of the chick heart was constricted using a ligature to increase cardiac pressure overload. Outflow tract-banding was performed at HH21, with harvesting at crucial valve development stages (HH26, HH29 and HH35). Although normal valve morphology was found in HH26 outflow tract banded hearts, smaller and dysmorphic mitral valve primordia were seen upon altered haemodynamics in histological and stereological analysis at HH29 and HH35. A decrease in apoptosis, and aberrant expression of a shear stress responsive gene and extracellular matrix markers in the endocardial cushions were seen in the chick HH29 outflow tract banded hearts. In addition, dysregulation of extracellular matrix (ECM) proteins fibrillin-2, type III collagen and tenascin were further demonstrated in more mature primordial mitral valve leaflets at HH35, with a concomitant decrease of ECM cross-linking enzyme, transglutaminase-2. These data provide compelling evidence that normal haemodynamics are a prerequisite for normal mitral valve morphogenesis, and abnormal blood flow could be a contributing factor in mitral valve defects, with differentiation as a possible underlying mechanism.

SUBMITTER: Pang KL

PROVIDER: S-EPMC5529288 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of altered haemodynamics on the developing mitral valve in chick embryonic heart.

Pang Kar Lai KL Parnall Matthew M Loughna Siobhan S

Journal of molecular and cellular cardiology 20170530

Intracardiac haemodynamics is crucial for normal cardiogenesis, with recent evidence showing valvulogenesis is haemodynamically dependent and inextricably linked with shear stress. Although valve anomalies have been associated with genetic mutations, often the cause is unknown. However, altered haemodynamics have been suggested as a pathogenic contributor to bicuspid aortic valve disease. Conversely, how abnormal haemodynamics impacts mitral valve development is still poorly understood. In order ...[more]

PMID: 28576718

Similar Datasets

Project description:ObjectiveIntraoperative predictors of functional mitral valve (MV) stenosis after surgical repair of mitral regurgitation (MR) caused by prolapse remain poorly characterised. This study evaluated the effect of annuloplasty size on postoperative MV haemodynamics during exercise and evaluated predictors of MV hemodynamics.Methods104 patients were randomly assigned to leaflet resection or preservation for surgical repair of MR in the Canadian Mitral Research Alliance CardioLink-2 study. In this post hoc analysis, we compared MV haemodynamics between the two surgical groups and examined the relationship between annuloplasty size and MV haemodynamics 1 year after repair in the combined groups. Echocardiograms were performed at baseline and intraoperatively. Exercise transthoracic echocardiography was performed 1 year postoperatively. Multivariable linear regression analysis was used to identify predictors of exercise MV gradients at follow-up.ResultsMean age of participants was 65±10 years, and 83% were male. Median annuloplasty size was 34 (IQR 32-36). Dividing by the median, 48 (46%) had annuloplasty size of <34 mm and 56 (54%) had ≥34 mm. Mean and peak exercise gradients at 1 year were 11±5 mm Hg and 22±9 mm Hg in <34, and 6±3 mm Hg and 14±5 mm Hg in ≥34 (p<0.001). Rate of residual MR was similar in both groups. In multivariable analyses, annuloplasty size of ≥34 mm was associated with lower mean and peak exercise gradients at 12 months, after adjustment for repair type, age, sex, heart rate and body surface area (β -4.1, 95% CI -6 to -3, p<0.001, and β -7 95% CI -10 to -4, p<0.001, respectively). Intraoperative mean and peak MV gradients by transesophageal echocardiography independently predicted mean and peak resting and exercise gradients at follow-up (p<0.001). Similar results were obtained in both leaflet resection and preservation.ConclusionAnnuloplasty size of ≥34 mm is associated with a 4 and 7 mm Hg reduction in mean and peak exercise MV gradients, respectively, 1 year post MV repair regardless of the repair strategy used. Intraoperative TEE MV gradients predict exercise MV gradients 1 year post repair.Trial registration numberNCT02552771.

Project description:ImportanceBioprosthetic mitral valves are implanted with increasing frequency but inevitably degenerate, leading to heart failure. Reoperation is associated with high morbidity and mortality. Transcatheter mitral valve-in-valve (MViV) using balloon-expandable transcatheter valves has emerged as an alternative for high-surgical risk patients.ObjectiveTo assess contemporary outcomes of SAPIEN 3 (Edwards Lifesciences) MViV replacement.Design, setting, and participantsIn this registry-based prospective cohort study of SAPIEN 3 MViV, patients entered in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry from June 2015 to July 2019 were analyzed. US Centers for Medicare and Medicaid linkage ensured comprehensive collection of death and stroke data.ExposuresMitral valve-in-valve for degenerated bioprosthetic mitral valves.Main outcomes and measuresThe primary efficacy end point was 1-year mortality. The primary safety end point was procedural technical success as defined by the Mitral Valve Academic Research Consortium criteria. Secondary end points included 30-day mortality, New York Heart Association-defined heart failure, and mitral valve performance.ResultsA total of 1529 patients (mean [SD] age, 73.3 [11.84] years; 904 women [59.1%]) underwent transseptal or transapical MViV implant at 295 hospitals between June 2015 and July 2019. The mean (SD) Society of Thoracic Surgeons predicted risk of mortality was 11.1% (8.7%). Procedural technical success was achieved for 1480 of 1529 patients (96.8%). All-cause mortality was 5.4% at 30 days and 16.7% at 1 year. Transseptal access was associated with lower 1-year all-cause mortality than transapical access (15.8% vs 21.7%; P = .03). Transcatheter MViV led to early, sustained, and clinically meaningful improvements in heart failure (class III/IV New York Heart Association heart failure of 87.1% at baseline vs 9.7% at 1 year). The mean (SD) mitral valve gradient at 1 year was 7 (2.89) mm Hg.Conclusions and relevanceTranscatheter MViV using the SAPIEN 3 transcatheter heart valve is associated with high technical success, low 30-day and 1-year mortality, significant improvement of heart failure symptoms, and sustained valve performance. Transseptal MViV should be considered an option for most patients with failed surgical bioprosthetic valves and favorable anatomy.

Dataset Information

Effect of altered haemodynamics on the developing mitral valve in chick embryonic heart.

Publications

Effect of altered haemodynamics on the developing mitral valve in chick embryonic heart.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets