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The association among age, early mitral leaflet closure, cardiac structure, diastolic indices and NT-proBNP in an asymptomatic Taiwanese population.

ABSTRACT: Advanced age is associated with left ventricular (LV) remodeling and impaired diastole. The association among aging, mitral leaflet closure (EF slope), cardiac structures, and diastolic indices in an asymptomatic Taiwanese population is largely unknown.We studied 8103 asymptomatic participants (49.5 ± 11.6 years, 38.2% women) from a health evaluation cohort (2004-2012) in a tertiary center in Taiwan. Echo-derived LV structure/function, and M-mode based EF slope (mm/s) and serum NT-proBNP level were obtained. The association between EF slope and the other clinical or echo-based parameters was investigated.Average values for EF slope among various age groups in the Taiwanese population were determined for both genders. Advanced age was associated with reductions in EF slope (adjusted estimate: - 0.35/per decade). Reduced EF slope was associated with older age, higher blood pressure and greater body mass index in multivariate models (all p < 0.05). Reduced EF slope was correlated with greater cardiac concentricity, abnormal E' and E/E' (AUROC: 0.74 and 0.77, respectively, both p < 0.05) and elevated NT-proBNP (Coef: 5.98 pg/mL, per - 10 mm/s EF slope, 95% CI: 7.82 to 4.17, p < 0.001). EF-slope also clearly discriminated individuals with abnormal estimated LV filling (E/E' categorized by < 8, ≥ 8 & < 15, ≥ 15, ANOVA p < 0.001).EF-slope reduction in the asymptomatic Taiwanese population was correlated with age, several unfavorable LV remodeling, and impaired diastolic function parameters, and EF-slope can be an effective clinical diagnostic tool for identifying poor E' and elevated LV filling pressure. In addition, our data provided reference values for EF-slope in various age groups.

SUBMITTER: Chen C

PROVIDER: S-EPMC5497255 | biostudies-other | 2015 Sep

REPOSITORIES: biostudies-other

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Project description:Rationale: Ischemic mitral regurgitation (IMR) is frequently observed following myocardial infarction (MI) and is associated with higher mortality and poor clinical prognosis if left untreated. Accumulating evidence suggests that mitral valve (MV) leaflets actively remodel post-MI, yet the cellular mechanisms underlying these responses and how this affects tissue function remain largely unknown. Objective: We sought to elucidate MV remodeling post-MI at the tissue, cellular, and transcriptomic levels. Methods and Results: The mechanical behavior of ovine MV leaflets pre-MI and 8 weeks post-MI reveal a significant decrease in radial direction extensibility, which essentially eliminated the mechanical anisotropy typically observed in healthy MVs. Quantitative histology and ultrastructural assessment by transmission electron microscopy revealed altered leaflet composition and architecture at 8 weeks post-MI. Assessment of the MV interstitial cell (MVIC) nuclear aspect ratio, a metric of cellular deformation, revealed that MVICs were on average rounder following MI. RNA sequencing (RNA-seq) indicated that YAP-induced genes were elevated at 4 weeks post-MI and genes related to extracellular matrix organization were some of the most downregulated in sheep with IMR compared to sheep without IMR at 4 weeks post-MI. Additionally, RNA-seq revealed the possible recruitment of immune cells in this remodeling process due to the drastic elevation of CXCL9 and CLEC10A. Conclusions: This multiscale assessment revealed significant mechanical and microstructural changes due to MI. RNA-seq provided a baseline for global gene expression changes in response to MI with and without IMR and suggests YAP-induced mechanotransduction, altered expression of ECM-related genes, and recruitment of immune cells as mechanisms contributing to altered MV biomechanics post-MI. Conclusions: This multiscale assessment revealed significant mechanical and microstructural changes due to MI. RNA-seq provided a baseline for global gene expression changes in response to MI with and without IMR and suggests YAP-induced mechanotransduction, altered expression of ECM-related genes, and recruitment of immune cells as mechanisms contributing to altered MV biomechanics post-MI.

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The association among age, early mitral leaflet closure, cardiac structure, diastolic indices and NT-proBNP in an asymptomatic Taiwanese population.

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