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BACKGROUND: Right ventricular (RV) fibrosis is an important pathological change that occurs during the development of right heart failure (RHF) induced by pulmonary hypertension (PH). Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been shown to play a major role in left heart failure, but it is unclear whether it has a positive effect on RHF. This study aimed to clarify the effect of DAPA on PH-induced RHF and investigate the underlying mechanisms. METHODS: We conducted experiments on two rat models with PH-induced RHF and cardiac fibroblasts (CFs) exposed to pathological mechanical stretch or transforming growth factor-beta (TGF-ß) to investigate the effect of DAPA. RESULTS: In vivo, DAPA could improve pulmonary hemodynamics and RV function. It also attenuated right heart hypertrophy and RV fibrosis. In vitro, DAPA reduced collagen expression by increasing the production of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). Additionally, DAPA was found to reduce reactive oxygen species (ROS) levels in CFs and the right heart in rats. Similar to DAPA, the ROS scavenger N-acetylcysteine (NAC) exerted antifibrotic effects on CFs. Therefore, we further investigated the mechanism by which DAPA promoted collagen degradation by reducing ROS levels. CONCLUSIONS: In summary, we concluded that DAPA ameliorated PH-induced structural and functional changes in the right heart by increasing collagen degradation. Our study provides new ideas for the possibility of using DAPA to treat RHF.
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Background: Myocardial work (MW) indices and longitudinal strain (LS) are sensitive markers of early left ventricular systolic dysfunction. Stress computed tomography myocardial perfusion imaging (CT-MPI) can assess early myocardial ischemia. The association between resting MW indices and stress myocardial perfusion remains unclear. This study compares resting MW indices with LS to assess stress myocardial perfusion in angina patients with non-obstructive coronary artery disease (CAD). Methods: Eighty-four patients who underwent resting echocardiography, coronary computed tomography angiography, and stress CT-MPI were reviewed. Seventeen myocardial segments were divided into three regions according to the epicardial coronary arteries. Global indices included global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Regional indices included regional longitudinal strain (RLS), regional work index (RWI), and regional work efficiency (RWE). Reduced global perfusion was defined as an average stress myocardial blood flow (MBF) <116 mL/100 mL/min for the whole heart. Reduced regional perfusion was defined as an average stress MBF <116 mL/100 mL/min for the coronary territories. No patients demonstrated obstructions in the epicardial coronary arteries (stenosis diameter <50%). The MW indices and LS were compared. Receiver operating characteristic curves were constructed and logistic regression analyses were used to investigate the predictors of reduced myocardial perfusion. Results: Patients with reduced stress perfusion demonstrated reduced GLS, GWI, GCW, and GWE (P<0.05) and increased GWW (P<0.05). After adjustment for age and sex, GWE was still independently associated with reduced myocardial perfusion (odds ratio =0.386, 95% confidence interval: 0.214-0.697; P<0.05). Receiver operating characteristic curves reflected the good diagnostic ability of GWE and its superiority to GLS (area under the curve: 0.858 vs. 0.741). The optimal cutoff GWE value was 95% (sensitivity, 70%; specificity, 90%). Regions with lower stress perfusion showed lower RLS, RWI, and RWE (P<0.05). The optimal cutoff value of RWE for predicting reduced regional perfusion was 95%, with an area under the curve of 0.780, a sensitivity of 62%, and a specificity of 83%. Conclusions: Resting MW indices perform well in assessing global and regional stress myocardial perfusion in angina patients with non-obstructive CAD, and GWE is superior to GLS in the global evaluations.
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We demonstrate the recently proposed nucleon energy-energy correlator (NEEC) f_{EEC}(x,θ) can unveil the gluon saturation in the small-x regime in eA collisions. The novelty of this probe is that it is fully inclusive just like the deep-inelastic scattering (DIS), with no requirements of jets or hadrons but still provides an evident portal to the small-x dynamics through the shape of the θ distribution. We find that the saturation prediction is significantly different from the expectation of the collinear factorization.