Citations

Background: Transcatheter aortic valve replacement (TAVR) is a well-established therapeutic option for all risk patients with symptomatic severe aortic stenosis (AS). While TAVR primarily addresses AS, its benefits extend beyond the valve itself. Recent studies suggest possible restoration of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) following TAVR. This study aims to assess changes in LV GLS in patients undergoing TAVR, which may serve as a subclinical indicator of improved LV mechanics. Materials and Methods: This retrospective study included patients with severe AS who underwent TAVR at the American University of Beirut Medical Center from January 2017 to January 2023. Baseline and 1-year echocardiography parameters were compared, and GLS was calculated to assess the impact of TAVR on LV function. Results: A total of 80 patients (mean age: 81.3 ± 7.8 years; 38.8% of women; 88.8% hypertensive) who underwent TAVR for severe AS were included in the final analysis. One-year post-TAVR, echocardiographic studies showed a significant reduction in interventricular septum diameter (13.3 ± 2.3 mm vs. 12 ± 1.8 mm, P < 0.001) and LV mass index (LVMI) (113.6 ± 26.6 g/m 2 vs. 96 ± 30.3 g/m 2 , P < 0.001). LVEF showed a modest improvement (59.2 ± 12.3% vs. 62.1 ± 7.6%, P < 0.01). LV GLS significantly improved from −16.8 ± 4.6% to −19.2 ± 3.3% ( P < 0.001). Baseline LVMI, LVEF, and GLS correlate with the GLS change (ΔGLS) post-TAVR. Conclusion: GLS significantly improves 1 year after TAVR, indicating an overall improvement in LV performance. The degree of improvement in GLS correlates with baseline LVMI and systolic function.

ABSTRACT Evidence indicates that the integrity of in utero development influences late life healthy or unhealthy aging; however, specific links between them are unclear. Histone chaperone HIRA is thought to play a role in both life stages, and here, we explore this role using the murine pigmentary system by investigating and comparing the effects of its lineage‐specific knockout, either conditionally during embryogenesis or postnatally. Embryonic knockout of Hira in tyrosinase+ neural crest‐derived lineages, including melanoblasts, led to reduced melanoblast numbers during embryogenesis, with single‐cell RNA sequencing analysis indicating evidence of lineage‐specificity defects. This was supported in an in vitro model using melb‐a melanoblasts in which Hira knockdown affected lineage identity and melanoblast differentiation potential, with ATAC‐seq data indicating a role of HIRA in orchestrating chromatin accessibility. Interestingly, however, newborn Hira knockout mice had wild type numbers of differentiated melanocytes, albeit functionally defective, as demonstrated by very mild hypopigmentation of the first hair coat, increased melanocyte telomere‐associated DNA damage foci, and impaired response to proliferative challenge. Moreover, as they aged, mice with embryonic melanoblast Hira knockout displayed marked defects in melanocyte stem cell maintenance and premature hair graying. Importantly, this phenotype was not observed after postnatal inducible knockout, indicating an essential role for HIRA at embryonic stages that is transmitted to adulthood, rather than a direct postnatal requirement within the pigmentary system. This genetic model shows that HIRA function during early development lays a foundation for maintaining lineage identity and subsequent maintenance of adult tissue‐specific stem cells during aging.