Association between Troponin Elevation and Decreased Myocardial Blood Flow Reserve in Patients without Obstructive Coronary Artery Disease.

INTRODUCTION: To study the prognostic factors of patients with chest pain and without obstructive coronary artery disease is of great significance for the management of such patients. We assessed whether a high-sensitivity troponin I (hs-TnI) is associated with prognosis in patients with chest pain and without obstructive coronary artery disease. METHODS: From 2011 to 2017, 489 consecutively hospitalized patients with chest pain and without significant coronary artery stenosis (<50%) were tested for hs-TnI and underwent stress myocardial contrast echocardiography (MCE). Myocardial blood flow reserve (MBFR) was measured by stress MCE. Patients were followed (median, 41 months) for composite endpoints, including cardiovascular death and non-fatal myocardial infarction. Cox proportional hazards models were performed to determine associations between hs-TnI and the composite endpoints. RESULTS: Among 489 patients with chest pain and without significant coronary artery stenosis, 257 patients (52.6%) had elevated hs-TnI. Compared to patients with normal hs-TnI, patients with elevated hs-TnI were older (p = 0.013) and had a higher prevalence of atrial fibrillation (p = 0.003), higher left ventricular mass index (p = 0.002) and E/e' septal (p < 0.001), and a lower MBFR (p < 0.001). After adjustment, there was still a significant association between hs-TnI and MBFR (odds ratio = 1.145; 95% confidence interval [CI], 1.079-1.214; p < 0.001). Compared with patients with normal hs-TnI, patients with elevated hs-TnI had a greater cumulative event rate (log-rank p = 0.002). Males (hazard ratio [HR], 4.770; 95% CI, 1.175-19.363; p = 0.029) and reduced MBFR (HR, 2.496; 95% CI, 1.446-4.311; p = 0.001) were risk factors associated with composite endpoints in patients with elevated hs-TnI. CONCLUSIONS: In patients with chest pain and without obstructive coronary artery disease, elevated hs-TnI is associated with decreased myocardial perfusion by contrast echocardiography as well as a higher incidence of cardiovascular events.

D2CFR: Minimize Counterfactual Regret With Deep Dueling Neural Network.

Counterfactual regret minimization (CFR) is a popular method for finding approximate Nash equilibrium in two-player zero-sum games with imperfect information. Solving large-scale games with CFR needs a combination of abstraction techniques and certain expert knowledge, which constrains its scalability. Recent neural-based CFR methods mitigate the need for abstraction and expert knowledge by training an efficient network to directly obtain counterfactual regret without abstraction. However, these methods only consider estimating regret values for individual actions, neglecting the evaluation of state values, which are significant for decision-making. In this article, we introduce deep dueling CFR (D2CFR), which emphasizes the state value estimation by employing a novel value network with a dueling structure. Moreover, a rectification module based on a time-shifted Monte Carlo simulation is designed to rectify the inaccurate state value estimation. Extensive experimental results are conducted to show that D2CFR converges faster and outperforms comparison methods on test games.

Cascaded Attention: Adaptive and Gated Graph Attention Network for Multiagent Reinforcement Learning.

Modeling the interactive relationships of agents is critical to improving the collaborative capability of a multiagent system. Some methods model these by predefined rules. However, due to the nonstationary problem, the interactive relationship changes over time and cannot be well captured by rules. Other methods adopt a simple mechanism such as an attention network to select the neighbors the current agent should collaborate with. However, in large-scale multiagent systems, collaborative relationships are too complicated to be described by a simple attention network. We propose an adaptive and gated graph attention network (AGGAT), which models the interactive relationships between agents in a cascaded manner. In the AGGAT, we first propose a graph-based hard attention network that roughly filters irrelevant agents. Then, normal soft attention is adopted to decide the importance of each neighbor. Finally, gated attention further refines the collaborative relationship of agents. By using cascaded attention, the collaborative relationship of agents is precisely learned in a coarse-to-fine style. Extensive experiments are conducted on a variety of cooperative tasks. The results indicate that our proposed method outperforms state-of-the-art baselines.

NLRP3 Inflammasome Is Involved in Calcium-Sensing Receptor-Induced Aortic Remodeling in SHRs.

Increasing evidence suggests that the NLRP3 (nucleotide oligomerization domain-like receptor family, pyrin domain containing 3) inflammasome participates in cardiovascular diseases. However, its role and activation mechanism during hypertension remains unclear. In this study, we tested the role and mechanism of calcium-sensing receptor (CaSR) in NLRP3 inflammasome activation during hypertension. We observed that the expressions of CaSR and NLRP3 were increased in spontaneous hypertensive rats (SHRs) along with aortic fibrosis. In vascular smooth muscle cells (VSMCs), the activation of NLRP3 inflammasome associated with CaSR and collagen synthesis was induced by angiotensin II (Ang II). Furthermore, inhibition of CaSR and NLRP3 inflammasome attenuated proinflammatory cytokine release, suggesting that CaSR-mediated activation of the NLRP3 inflammasome may be a therapeutic target in aortic dysfunction and vascular inflammatory lesions.

Involvement of mitochondrial fission in calcium sensing receptor-mediated vascular smooth muscle cells proliferation during hypertension.

Hyperproliferation of vascular smooth muscle cells (VSMC) is a major risk factor for cardiovascular diseases. Proper mitochondrial fission and fusion is involved with VSMC function. However, the role and mechanism of mitochondrial morphological changes in VSMC proliferation are not well understood. Here, we found that calcium sensing receptor (CaSR) was increased in the aortas from spontaneous hypertensive rats (SHRs) compared with age-matched Wistar Kyoto (WKY) rats. There was also an increase in mitochondrial fission and VSMC proliferation, which was attenuated by Calhex231. In primary rat VMSC, angiotensin II (Ang II) stimulation induced cytosolic [Ca2+]i increase, mitochondrial shortening and proliferation, all of which could be attenuated by pretreatment with mitochondrial division inhibitor-1 (Mdivi-1) and Calhex231. Our data indicate that CaSR-mediated mitochondrial fission could be a therapeutic target for hyperproliferative disorders.

Combined myocardial deformation to predict cardiac resynchronization therapy response in nonischemic cardiomyopathy.

BACKGROUND: 20-30% of patients do not benefit from cardiac resynchronization therapy (CRT) when the established selection criteria were applied. We hypothesized that a combined assessment of mechanical dyssynchrony, myocardial deformation, and diastolic function would identify patients who would benefit most from CRT. METHOD: In 36 CRT patients, clinical evaluation and echocardiography were performed before and after CRT. Patients were classified into three subgroups according to their amount of response: echocardiographic responders, clinical responders, and nonresponders. Radial dyssynchrony and left ventricular (LV) global longitudinal, radial, and circumferential peak strain was assessed by speckle-tracking image. Diastolic function was quantified by conventional echocardiography. RESULT: In addition to left bundle branch block, nonspecific intraventricular conduction disturbance with intraventricular dyssynchrony could also improve LV remodeling. Echocardiographic responders had better global longitudinal strain, global circumferential peak strain, and global radial strain at baseline which significantly increased at 12-month follow-up. An improvement in estimates of LV filling pressure and a decrease in mitral regurgitation and left atrial dimensions were observed only in echocardiographic responders to CRT. Patients with clinical but without echocardiographic response showed a significant improvement in atrioventricular (AV) synchrony and a nonsignificant improvement in other parameters. The nonresponder group did not improve the AV and intraventricular dyssynchrony. CRT could not improve restrictive filling pattern with normal filling time. Overall, those patients with AV and intraventricular dyssynchrony and those with best contractile function and short diastolic filling time of restrictive filling pattern at baseline demonstrated the greatest benefit from CRT. CONCLUSIONS: Mechanical dyssynchrony, contractile function, and filling pattern are important determinants of the benefits in CRT.