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Background Arrhythmogenic cardiomyopathy (AC) is characterized by biventricular dysfunction, exercise intolerance, and high risk of ventricular tachyarrhythmias and sudden death. Predisposing factors for left ventricular (LV) disease manifestation and its prognostic implication in AC are poorly described. We aimed to assess the associations of exercise exposure and genotype with LV dysfunction in AC, and to explore the impact of LV disease progression on adverse arrhythmic outcome. Methods and Results We included 168 patients with AC (50% probands, 45% women, 40±16 years old) with 715 echocardiographic exams (4.1±1.7 exams/patient, follow-up 7.6 [interquartile range (IQR), 5.4-10.9] years) and complete exercise and genetic data in a longitudinal study. LV function by global longitudinal strain was -18.8% [IQR, -19.2% to -18.3%] at presentation and was worse in patients with greater exercise exposure (global longitudinal strain worsening, 0.09% [IQR, 0.01%-0.17%] per 5 MET-hours/week, P=0.02). LV function by global longitudinal strain worsened, with 0.08% [IQR, 0.05%-0.12%] per year; (P less then 0.001), and progression was most evident in patients with desmoplakin genotype (P for interaction less then 0.001). Deterioration of LV function predicted incident ventricular tachyarrhythmia (aborted cardiac arrest, sustained ventricular tachycardia, or implantable cardioverter defibrillator shock) (adjusted odds ratio, 1.1 [IQR, 1.0-1.3] per 1% worsening by global longitudinal strain; P=0.02, adjusted for time and previous arrhythmic events). Conclusions Greater exercise exposure was associated with worse LV function at first visit of patients with AC but did not significantly affect the rate of LV progression during follow-up. Progression of LV dysfunction was most pronounced in patients with desmoplakin genotypes. Deterioration of LV function during follow-up predicted subsequent ventricular tachyarrhythmia and should be considered in risk stratification.Background Edge-to-edge transcatheter mitral valve repair as salvage therapy in high surgical risk patients with severe mitral regurgitation presenting with cardiogenic shock (CS) has been described in small case series, but large clinical results have not been reported. This study aimed to evaluate outcomes of transcatheter mitral valve repair with MitraClip in patients with mitral regurgitation and CS using a large national database. Methods and Results From January 2014 to March 2019, we identified hospitalizations for CS in patients with mitral valve disease using data from Centers for Medicare and Medicaid Services. Those with a prior surgical or percutaneous mitral valve intervention were excluded. We compared survival between patients who underwent MitraClip during the index hospitalization and those who did not using propensity-matched analysis. The analysis included 38 166 patients (mean age, 71±11 years, 41.6% women) of whom 622 (1.6%) underwent MitraClip. MitraClip was increasingly used during CS hospitalizations over the study period (P less then 0.001). After matching, patients receiving MitraClip had significantly lower in-hospital mortality (odds ratio, 0.6; 95% CI, 0.47-0.77; P less then 0.001) and 1-year mortality (hazard ratio, 0.76; 95% CI, 0.65-0.88; P less then 0.001) compared with those without MitraClip. The survival benefit associated with MitraClip was consistent across subgroups of interest, with the exception of patients requiring acute mechanical circulatory support or hemodialysis at index. Conclusions In patients with mitral regurgitation presenting with CS, use of MitraClip is increasing and associated with greater in-hospital and 1-year survival. Further studies are warranted to optimize patient selection and procedure timing for those receiving MitraClip as a treatment option in CS.Background Cardiac hypertrophy is an independent risk factor for heart failure, a leading cause of morbidity and mortality globally. The calcineurin/NFAT (nuclear factor of activated T cells) pathway and the MAPK/Erk (extracellular signal-regulated kinase) pathway contribute to the pathogenesis of cardiac hypertrophy as an inter-dependent network of signaling cascades. However, how these pathways interact remains unclear, and specifically few direct targets responsible for the pro-hypertrophic role of NFAT have been described. Methods By engineering a cardiomyocyte-specific ETS2 (a member of E26 transformationspecific sequence (ETS)-domain family) knockout mice, we investigated the role of ETS2 in cardiac hypertrophy. NSC27223 Primary cardiomyocytes were also used to evaluate ETS2 function in cell growth. Results ETS2 is phosphorylated and activated by Erk1/2 upon hypertrophic stimulation in both mouse (n = 3) and human heart samples (n = 8-19). Conditional deletion of ETS2 in mouse cardiomyocytes protects against pre target genes.Many reports have indicated that long non-coding RNAs (lncRNAs) are closely associated with the occurrence and development of various cancers. Musculin antisense RNA 1 (MSC-AS1) is a an lncRNA known to act as an oncogene in several types of human cancers; however, its specific function in lung adenocarcinoma (LUAD) is still unclear. For this study, we designed and conducted experiments to clarify the function of the lncRNA MSC-AS1 in LUAD and its underlying mechanisms. We found that the expression of MSC-AS1 was significantly higher in LUAD tissues and cells than that in normal ones. Through loss-of function assays, we confirmed that the proliferation of LUAD cells was significantly restrained by down-regulation of MSC-AS1 and the rate of cell apoptosis was accelerated. The results from our mechanistic experiments showed that MSC-AS1 interacts with microRNA-33b-5p (miR-33b-5p). Moreover, glycerol-3-phosphate acyltransferase, mitochondrial (GPAM) was found to be a direct target gene of miR-33b-5p, and it has similar functions to MSC-AS1. Further, inhibition of miR-33b-5p or overexpression GPAM reversed the inhibitory effects of MSC-AS1 silencing on LUAD cell growth. In short, MSC-AS1 facilitates LUAD progression through sponging miR-33b-5p to up-regulate GPAM.
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