Atrial standstill associated with lamin A/C mutation: A case report.

The case report shares evidence for a better understanding of atrial standstill. This being a rare arrhythmogenic condition. This is a 46-year-old woman presented with multiple sites of arterial embolism, including lower extremity arteries, coronary artery, and cerebral artery. Unexpectedly, multiple arterial embolization in the patient was due to atrial standstill by transthoracic echocardiography and cardiac electrophysiological study. An additional family investigation revealed that the patient's brother and sister also suffered from this disease. In search of further understanding the case, we carried out the genetic testing of the family and a frame shift double-G insertion mutation at c.1567 in the LMNA gene was found in all the three individuals. The patient recovered well after anticoagulation therapy and left bundle branch area pacing. This report remarks on the importance of multiple sites of arterial embolism which should be wary of family atrial standstill.

Case report: Dual atrioventricular nodal non-reentrant tachycardia with six types of ECG patterns leading to tachycardia-induced cardiomyopathy in a 51-year-old man.

More than three types of ECG manifestations in one patient with dual atrioventricular nodal non-reentrant tachycardia (DAVNNT) are rare. We report a 51-year-old male patient with DAVNNT consisting of six types of ECG patterns leading to tachycardia-induced cardiomyopathy. After radiofrequency ablation of the slow pathway, DAVNNT was eliminated and cardiac function was restored.

MicroRNAs sequencing of plasma exosomes derived from patients with atrial fibrillation: miR-124-3p promotes cardiac fibroblast activation and proliferation by regulating AXIN1

MicroRNAs (miRNAs) play an important role in the pathogenesis of atrial fibrillation (AF). Exosomal miRNAs may develop as promising biomarkers for AF. To explore significant exosomal miRNAs in AF, plasma exosomes were extracted from 3 patients with AF and 3 patients with sinus rhythm (SR), respectively. Differential expression of exosomal miRNAs were screened by high-throughput sequencing analysis and verified by qRT-PCR from 40 patients with AF and 40 patients with SR. The target genes prediction, biological function, and signaling pathways analysis were conducted by miRanda software, gene ontology (GO), and KEGG analysis. The results showed that there were 40 differently expressed exosomal miRNAs from AF patients compared with SR patients, of which 13 miRNAs were upregulated and 27 miRNAs were downregulated. qRT-PCR validation demonstrated that miR-124-3p, miR-378d, miR-2110, and miR-3180-3p were remarkably upregulated, while miR-223-5p, miR-574-3p, miR-125a-3p, and miR-1299 were downregulated. To explore the function of miR-124-3p associated with AF, plasma exosomes derived from AF patients were co-incubated with rat myocardial fibroblasts. The expression of miR-124-3p was upregulated in myocardial fibroblasts. The viability and proliferation of myocardial fibroblasts were elevated by transfecting with miR-124-3p overexpression plasmids using CCK8 and immunofluorescence-staining methods. AXIN1 was verified to be the target of miR-124-3p by luciferase assay in vitro. Expression of AXIN1 was reduced, while β-catenin, Collagen 1, and α-SMA were increased in myocardial fibroblasts with miR-124-3p overexpression. In conclusion, these findings suggested that circulating exosomal miRNAs may serve as novel biomarkers for AF, and miR-124-3p promotes fibroblast activation and proliferation through regulating WNT/β-catenin signaling pathway via AXIN1. (AU)

MicroRNAs sequencing of plasma exosomes derived from patients with atrial fibrillation: miR-124-3p promotes cardiac fibroblast activation and proliferation by regulating AXIN1.

MicroRNAs (miRNAs) play an important role in the pathogenesis of atrial fibrillation (AF). Exosomal miRNAs may develop as promising biomarkers for AF. To explore significant exosomal miRNAs in AF, plasma exosomes were extracted from 3 patients with AF and 3 patients with sinus rhythm (SR), respectively. Differential expression of exosomal miRNAs were screened by high-throughput sequencing analysis and verified by qRT-PCR from 40 patients with AF and 40 patients with SR. The target genes prediction, biological function, and signaling pathways analysis were conducted by miRanda software, gene ontology (GO), and KEGG analysis. The results showed that there were 40 differently expressed exosomal miRNAs from AF patients compared with SR patients, of which 13 miRNAs were upregulated and 27 miRNAs were downregulated. qRT-PCR validation demonstrated that miR-124-3p, miR-378d, miR-2110, and miR-3180-3p were remarkably upregulated, while miR-223-5p, miR-574-3p, miR-125a-3p, and miR-1299 were downregulated. To explore the function of miR-124-3p associated with AF, plasma exosomes derived from AF patients were co-incubated with rat myocardial fibroblasts. The expression of miR-124-3p was upregulated in myocardial fibroblasts. The viability and proliferation of myocardial fibroblasts were elevated by transfecting with miR-124-3p overexpression plasmids using CCK8 and immunofluorescence-staining methods. AXIN1 was verified to be the target of miR-124-3p by luciferase assay in vitro. Expression of AXIN1 was reduced, while ß-catenin, Collagen 1, and α-SMA were increased in myocardial fibroblasts with miR-124-3p overexpression. In conclusion, these findings suggested that circulating exosomal miRNAs may serve as novel biomarkers for AF, and miR-124-3p promotes fibroblast activation and proliferation through regulating WNT/ß-catenin signaling pathway via AXIN1.

Relationship between serum uric acid levels and different types of atrial fibrillation: An updated meta-analysis.

AIM: Increasing evidence supports the hypothesis that high serum uric acid (SUA) levels are related to atrial fibrillation (AF). However, the incidence of AF in patients with hyperuricemia and SUA levels in different types of AF is not entirely clear. This meta-analysis was designed to evaluate the relationship between SUA and incidence of AF, and the variation in SUA levels in different types of AF. DATA SYNTHESIS: Relevant reports were searched for in Embase, PubMed and the Cochrane Library. A fixed-effects model combining relative risk (RR) and the corresponding 95% confidence interval (95% CI) was used to evaluate the correlation between SUA and AF. The standardized mean differences (SMDs) of SUA values were calculated using a random-effects model to evaluate the differences in SUA levels among different types of AF. A total of 31 studies with 504,958 participants were included in this research. The results from 8 cohort studies showed that high SUA levels significantly increased the incidence of AF [RR (95% CI): 1.92 (1.68-2.20); P < 0.01]. The results from 29 studies revealed that SUA levels elevated in patients with AF [SMD (95% CI): 0.55 (0.43-0.66); P < 0.001]. Meanwhile, SUA levels in new-onset AF [SMD (95%CI): 0.24 (0.10-0.38); P = 0.001], paroxysmal AF [SMD (95%CI): 0.52 (0.33-0.72); P < 0.001] and persistent AF [SMD (95%CI): 1.23 (0.98-1.48); P < 0.001] were significantly higher than that in patients without AF. CONCLUSIONS: High SUA levels had an obvious correlation with the occurrence rate of AF. In addition, SUA levels were significantly different among patients with new-onset, paroxysmal and persistent AF.

Aortic Elasticity Evaluated by Pulsed Tissue Doppler Imaging of the Ascending Aorta in Different Diseases: A Systematic Review.

Several methods have been applied for the evaluation of aortic elasticity. Pulsed tissue Doppler imaging of the ascending aorta is a noninvasive method applied for the evaluation of aortic elasticity in wide variety of diseases which are reviewed in this study. A comprehensive systematic literature search was carried out in November 2019 using the English databases including PubMed, Scopus, Science Direct, and Embase. All references of eligible articles and published reviews on tissue Doppler imaging were searched for relevant publications. Data were extracted according to predefined criteria (including country of study origin, patient population, number of patients in case and control groups, and results of aortic elasticity evaluation in the specific patient groups compared with controls). Two independent reviewers extracted the data, and the results were checked, compared, and edited by the third reviewer. No formal assessment of the statistics of the primary data was made. The results showed that decreased aortic elasticity is not only present in cardiovascular diseases but also can be identified in diseases of other systems that affect cardiovascular system.

Impacts of CYP2C19 Polymorphism and Clopidogrel Dosing on in-Stent Restenosis: A Retrospective Cohort Study in Chinese Patients.

OBJECTIVE: This retrospective cohort study is to analyze the impacts of CYP2C19 polymorphism and clopidogrel dosing on in-stent restenosis (ISR) after coronary stenting. METHODS: Totally, 111 patients were included, who underwent percutaneous coronary intervention (PCI) with drug-eluting stent. Patients received clopidogrel treatment after the intervention on the background treatment with aspirin, based on the genotypes: 75 mg clopidogrel once each day for subjects without CYP2C19 loss-of-function (LOF) alleles (n=51; EM), 75 mg clopidogrel once each day (n=27; IM75) or twice each day (n=33; IM150) for subjects with one CYP2C19 LOF allele. ISR at 3-18 months after coronary stenting was assessed. RESULTS: ISR rate was significantly higher in the IM75 group (40.7%) than the EM group (11.8%). ISR rate in the IM150 group was lower than the IM75 group (6.1% vs 40.7%), and comparable to that in the EM group. Multivariate logistic regression showed that both CYP2C19 genotype and clopidogrel dosing were associated with the risk of ISR after adjusting the relevant confounding factors. ISR risk was higher in the IM patients than the EM patients. Patients with clopidogrel dose of 75 mg once each day had significantly higher risk of ISR than those with the dose of 75 mg twice each day. CONCLUSION: Increased dose of clopidogrel may reduce the risk of ISR after PCI in CYP2C19 LOF allele(s) carriers. The presence of CYP2C19 LOF allele(s) increases the risk of ISR after stenting, which could be counteracted by the increased dose of clopidogrel.

Visible-light-assisted condensation of ultrasonically atomized water vapor on LiNbO3:Fe crystals.

Optically massive trapping of the moisture in the air into an adjacent surface is a potential technique in the fields of bacterial adhesion and microfluidic generation, which is quite important to the development of LN-based biological lab-on-chips. Here we demonstrate on a LiNbO3:Fe substrate the visible-light-assisted condensation of the water vapor in a flowing stream created by an ultrasonic atomizer. Through analyzing the dynamic processes of the visible-light-assisted water condensation at different illumination intensities, it is found that the extent of the water condensation, the bending angle of water vapor trails and the interaction range of the condensation effect are highly dependent on the illumination intensity. According to these findings and the simulated trajectories of the water vapor stream at different illumination intensities, we propose that this visible-light-assisted water condensation is an aggregation process of tiny water droplets driven by the dielectrophoretic interaction of inhomogeneous photovoltaic field and also an electrostatic screening course of photovoltaic charges through the charged evaporation of condensed water. The prolonged condensation of water vapor after a high-intensity illumination and that of oil vapor at a super-low evaporation rate are also studied, and the agreement between the simulation and experimental results reinforces the above mechanism. The reported technique, employing the inexpensive, safe-for-cell visible laser beam, is quite convenient for the controllable generation of various biological microdroplets, and thus it is promising for the microfluidic functionality integration of LN-based biological lab-on-chips.

Increased Serum Concentrations of TNF-Like Weak Inducer of Apoptosis Predict Higher 28-Day Mortality in Patients with Sepsis.

We performed the current study to explore potential predictive value of serum Tumor Necrosis Factor- (TNF-) like weak inducer of apoptosis (TWEAK) concentrations for 28-day mortality in patients with sepsis. Adult septic patients (age≥18 years) admitted to a general ICU between November 2016 and October 2017 were consecutively included in our prospective observational study. TWEAK concentrations were detected in septic patients and healthy controls. Dynamic changes of TWEAK concentrations between 1st day and 3rd day of admission to ICU (ΔTWEAK concentrations) were also measured. A total of 79 septic patients were included and 19 of them (24.1%) died after a follow-up period of 28 days. We identified arterial lactate, NT-proBNP, and male gender as independent factors for 28-day mortality of patients with sepsis. The serum levels of TWEAK were significantly lower in septic patients compared to controls (417.4 ± 196.7 pg/ml versus 1243.8 ± 174.3 pg/ml, p<0.001). We found a positive correlation between TWEAK concentrations and SOFA score (Spearman correlation coefficient 0.235, p=0.037). Area under the receiver operating characteristic curve (AUROC) of ΔTWEAK concentrations for 28-day mortality was 0.754 (95% CI 0.645-0.844). We also evaluated the diagnostic performance of combinative index (ΔTWEAK concentrations and lactate) and obtained an AUROC of 0.860 (95% CI 0.763-0.928). In conclusion, our study found lower TWEAK concentrations in septic patients than those in healthy controls. Furthermore, the increased TWEAK concentrations during disease process predict higher 28-day mortality in septic patients. Dynamic changes of TWEAK should be an important supplement for current prognostic markers.

TWEAK/Fn14 mediates atrial-derived HL-1 myocytes hypertrophy via JAK2/STAT3 signalling pathway.

Atrial myocyte hypertrophy is one of the most important substrates in the development of atrial fibrillation (AF). The TWEAK/Fn14 axis is a positive regulator of cardiac hypertrophy in cardiomyopathy. This study therefore investigated the effects of Fn14 on atrial hypertrophy and underlying cellular mechanisms using HL-1 atrial myocytes. In patients with AF, Fn14 protein levels were higher in atrial myocytes from atrial appendages, and expression of TWEAK was increased in peripheral blood mononuclear cells, while TWEAK serum levels were decreased. In vitro, Fn14 expression was up-regulated in response to TWEAK treatment in HL-1 atrial myocytes. TWEAK increased the expression of ANP and Troponin T, and Fn14 knockdown counteracted the effect. Inhibition of JAK2, STAT3 by specific siRNA attenuated TWEAK-induced HL-1 atrial myocytes hypertrophy. In conclusion, TWEAK/Fn14 axis mediates HL-1 atrial myocytes hypertrophy partly through activation of the JAK2/STAT3 pathway.

Acute tuberculous myopericarditis mimicking acute myocardial infarction: A case report and literature review.

A number of cases of acute myopericarditis mimicking acute myocardial infarction (AMI) have previously been reported in the literature. However, to the best of our knowledge, such a case resulting from Mycobacterium tuberculosis infection has not previously been described. The present study reports the case of a 21-year-old male patient presenting with acute chest pain, in whom focal ST-segment elevation and elevated cardiac enzymes mimicked a diagnosis of AMI. However, acute tuberculous myopericarditis was diagnosed on the basis of a variety of imaging examinations, laboratory tests, as well as the changes observed in electrocardiograms (ECGs) and in the cardiac enzyme levels. The case highlights the importance of a detailed collection of medical history, comprehensive explanations of serial ECGs, thoracic computed tomography, echocardiogram and coronary angiography in the diagnosis and differentiation of acute tuberculous myopericarditis mimicking AMI.

Acute Myocardial Infarction in a Young Man with Hyperhomocysteinemia and Pulmonary Tuberculosis.

Acute myocardial infarction, hyperhomocysteinemia and pulmonary tuberculosis (PTB) are rare in individuals under the age of 30 years. We herein report the case of a 27-year-old man who presented with intermittent chest pain, elevated homosysteine level, and PTB. The patient was treated successfully with a combination of medications and percutaneous coronary intervention. This uncommon case highlights that homocysteine, folate and B vitamins levels should be regularly evaluated, and that chest X-rays or thoracic computed tomography should be ordered routinely to exclude PTB in patients under the age of 30 years who present acute myocardial infarction and lack the traditional risk factors.

Role of tumor necrosis factor alpha in the pathogenesis of atrial fibrillation: A novel potential therapeutic target?

Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice and a major cause of morbidity and mortality. Although the fundamental mechanisms underlying AF remain incompletely understood, atrial remodeling, including structural, electrical, contractile, and autonomic remodeling, has been demonstrated to contribute to the substrate for AF maintenance. Accumulating evidence shows that tumor necrosis factor alpha (TNF-α) plays exceedingly important roles in atrial remodeling. This article reviews recent advances in the roles of TNF-α in the pathogenesis of AF, elucidates the related mechanisms, and exploits its potential usefulness as a novel therapeutic target.

The role of TWEAK/Fn14 in cardiac remodeling.

The pathophysiological basis of heart failure is cardiac remodeling, a process that comprises structural and functional changes including cardiomyocyte proliferation, hypertrophy, necrosis, apoptosis, autophagy, interstitial fibrosis, contractile dysfunction and ventricular dilatation. Accumulating evidence demonstrate that tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is involved in the process by binding its receptor fibroblast growth factor-inducible molecule 14 (Fn14). In this review, we will discuss the potential role of the TWEAK/Fn14 axis in cardiac remodeling, elucidate its possible mechanisms and explore new therapeutic targets for heart failure.

TWEAK/Fn14 promotes the proliferation and collagen synthesis of rat cardiac fibroblasts via the NF-кB pathway.

We wished to elucidate a potential role of the tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible molecule 14 (Fn14) axis in myocardial fibrosis. Stimulation of neonatal rat cardiac fibroblasts (CFs) with TWEAK could increase CFs numbers and collagen synthesis. Conversely, when CFs were pretreated with siRNA against Fn14, induction of cell proliferation and collagen synthesis by TWEAK were inhibited. Pretreatment with TWEAK on CFs induced activation of the nuclear factor-kappaB (NF-кB) pathway and subsequently increased the production of metalloproteinase-9 (MMP-9). Cell treatment with siRNA against Fn14 led to inhibition of the NF-кB pathway. Additionally, after stimulation of cell with ammonium pyrrolidine dithiocarbamate, cell proliferation and collagen synthesis induced by NF-кB and the upregulation of MMP-9 production were inhibited. The present study suggested that the TWEAK/Fn14 axis increased cell proliferation and collagen synthesis by activating the NF-кB pathway and increasing MMP-9 activity. This axis may be important for regulating myocardial fibrosis.

Increased plasma osteoprotegerin levels are associated with the presence and severity of acute coronary syndrome.

OBJECTIVE: The objective of this study was to explore the relationship between increased plasma osteoprotegerin (OPG) levels and acute coronary syndrome (ACS). METHODS: Plasma OPG levels from 85 subjects undergoing coronary artery angiography in three different groups, including ACS (n=45), stable angia pectoris (SAP) (n=20) and normal coronary artery (NCA) (n=20), were detected by ELISA. Twenty-two ascending aorta specimens were surgically taken from 8 ACS, 7 SAP and 7 NCA patients, and OPG mRNA expression in the specimens was detected by RT-PCR. In addition, 10 coronary artery sections each were selected from autopsy archives for the presence of vulnerable atherosclerosis plaques (VP), stable plaques (SP) or no plaques (NP) and OPG protein expression in the sections was detected by immunohistochemistry. RESULTS: Plasma OPG concentrations in the ACS group were significantly higher than those in the SAP or NCA group.The levels of plasma OPG in the 1-, 2- and 3-vessel disease subgroups of ACS were increasingly higher (P < 0.05 or 0.01). Multiple logistic regression analyses revealed a significant independent relation between plasma OPG concentration and the presence of ACS (P = 0.032, odd ratio = 1.006).Ascending aorta specimens from the ACS group had a greater OPG mRNA expression than those from the NCA or SAP group (P < 0.01). Sections with VP had a markedly higher OPG expression than sections with SP or NP (P < 0.05 and P < 0.01, respectively). CONCLUSIONS: Increased plasma osteoprotegerin levels are associated with the presence and severity of acute coronary syndrome.

A high association of aortic valve sclerosis detected by transthoracic echocardiography with coronary arteriosclerosis.

OBJECTIVE: To examine whether aortic valve sclerosis (AVS) detected by transthoracic echocardiography (TTE) has a high association with coronary arteriosclerosis. METHODS: Clinical and angiographic features and TTE findings were retrospectively analyzed in a blinded fashion for 138 consecutive patients, of whom 58 had AVS and 80 had non-AVS diseases. Both histological and immunohistochemical studies were performed on frozen aortic valve sections obtained at autopsy from 7 AVS and 3 non-AVS patients. RESULTS: AVS and coronary artery disease (CAD) had similar clinical risk factors. The AVS group had a higher positive rate of coronary angiography and a higher incidence rate of multivessel CAD than the non-AVS group. The sensitivity, specificity, positive predictive value and negative predictive value of AVS in diagnosing CAD were 63.8, 71.3, 61.7 and 73.1%, respectively. Early lesions of AVS were characterized by accumulation of lipid and infiltration of macrophages and T lymphocytes as indicated by immunohistochemical staining. Late lesions were characterized by formation of calcific plaques, proliferation of fibrous connective tissue and immunohistochemical staining identifying a few macrophages or T lymphocytes and little lipid accumulation on the surface of aortic valve leaflets. Late lesions in the basement of aortic valve leaflets were characterized by hyperplastic granulation tissues. Three aortic valve leaflets from the non-AVS group were characterized by nonspecific thickened tips, increased collagen, no calcification, no lipid accumulation and no inflammatory cells. CONCLUSIONS: There were significant similarities in clinical risk factors, histopathological alterations of AVS and coronary atherosclerosis. AVS detected by TTE had a high association with coronary arteriosclerosis.