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AIMS: Left ventricular global longitudinal strain (LVGLS) is a known outcome predictor in transcatheter edge-to-edge repair (TEER) for functional mitral regurgitation (MR). We aimed to assess its prognostic yield in the setting of TEER for chronic primary MR. METHODS AND RESULTS: We conducted a single-center, retrospective analysis of 323 consecutive patients undergoing isolated, first-time procedures. Stratified by baseline LVGLS quartiles (≤-19%, -18.9-(-16)%, -15.9-(-12)%, > -12%), the cohort was evaluated for the primary composite outcome of all-cause mortality or heart failure hospitalizations, as well as secondary endpoints consisting of mitral reinterventions and the persistence of significant residual MR and/or functional disability - all along the first year after intervention. Subjects with worse (i.e., less negative) LVGLS exhibited higher comorbidity, more advanced HF, and elevated procedural risk. Post-TEER, those belonging to the worst LVGLS quartile group sustained increased mortality (16.9 vs 6.3%, Log-Rank p = 0.005, HR 1.75, 95% CI 1.08-4.74, p = 0.041) and, when affected by LV dysfunction/dilatation, more primary outcome events (21.1 vs 11.5%, Log-Rank p = 0.037, HR 1.68, 95% CI 1.02-5.46, p = 0.047). No association was demonstrated with other endpoints. Upon exploratory analysis, 1-month postprocedural LVGLS directly correlated with and was worse than its baseline counterpart by 1.6%, and a more impaired 1-month value - but not the presence/extent of deterioration - conferred heightened risk for the primary outcome. CONCLUSION: TEER for chronic primary MR is feasible, safe, and efficacious irrespective of baseline LVGLS. Yet, worse baseline LVGLS forecasts a less favorable postprocedural course, presumably reflecting a higher-risk patient profile.
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Background: Valve thrombosis is a well-documented cause of bioprosthetic valve failure. Case reports have been published of prosthetic valve thrombosis secondary to COVID-19 infection. This is the first case report of COVID-19 associated valve thrombosis in a patient with transcatheter aortic valve replacement (TAVR). Case summary: A 90-year-old female with atrial fibrillation on therapeutic apixaban and status-post TAVR presented with COVID-19 infection and was found to have severe bioprosthetic valvular regurgitation with features suggestive of valve thrombosis. She underwent valve-in-valve TAVR with resolution of valvular dysfunction. Discussion: This case report contributes to a growing body of evidence describing the occurrence of thrombotic complications in patients with valve replacement and COVID-19 infection. Increased vigilance and continued investigation are warranted to better characterize thrombotic risk and to inform optimal antithrombotic strategies during COVID-19 infection.
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Histone modifications, such as lysine methylation, acetylation and ubiquitination, are epigenetic tags that shape the chromatin landscape and regulate transcription required for synaptic plasticity and memory. Here, we show that transcription-promoting histone H3 trimethylated at lysine 4 (H3K4me3), histone H3 acetylated at lysine 9 and 14 (H3K9/14ac), and histone H2B monoubiquitinated at lysine 120 (H2BK120ub) are enhanced after the induction of long-lasting chemically-induced long-term potentiation (cLTP) in the murine hippocampus. While H3K4me3 and H3K9/14ac were transiently upregulated, H2BK120ub levels oscillated after cLTP induction. In addition, we present results showing that blocking the proteasome, a molecular complex specialized for targeted protein degradation, inhibited the upregulation of these epigenetic tags after cLTP. Thus, our study provides the initial steps toward understanding the role of the proteasome in regulating histone modifications critical for synaptic plasticity.