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Background: Exosomes are membrane vesicles that are actively secreted in response to microenvironmental stimuli. In this study, we quantified the amount of exosomes in patients with significant coronary artery disease (CAD) and evaluated its relationship with myocardial perfusion imaging (MPI) results. Methods: Patients who underwent both MPI and coronary angiography were recruited. Plasma was collected during angiography, and exosomes were extracted via the precipitation method. The summed stress scores (SSS), summed difference scores, and ventricular functional parameters were calculated from the MPI and compared with the amounts of exosomes and extracted miRNAs. Results: In total, 115 patients were enrolled (males: 78 %; mean age: 66.6 ± 10.6 years). Those with abnormal SSS according to the MPI had significantly fewer exosomes (p = 0.032). After multivariate analysis, the SSS remained significantly related to the amount of exosomes (p = 0.035). In forty randomly selected samples, miRNA-432–5p and miRNA-382–3p were upregulated in patients with abnormal SSS. Conclusion: Patients with compromised poststress myocardial perfusion on MPI tended to have fewer exosomes in association with CAD-related miRNAs. This is the first study to clarify the fundamental and pathophysiological causes of CAD using radiographic examinations.

Objective: In patients with atrial fibrillation (AF) and end-stage renal disease (ESRD), oral anticoagulants are contraindicated, and left atrial appendage occlusion (LAAO) is an alternative treatment. However, the efficacy of thromboembolic prevention using LAAO in these patients has rarely been reported in Asian populations. To our knowledge, this is the first long-term LAAO study in patients with AF undergoing dialysis in Asia. Methods: In this study, 310 patients (179 men) with a mean age of 71.3 ± 9.6 years and mean CHA2DS2-VASc 4.2 ± 1.8 were consecutively enrolled at multiple centers in Taiwan. The outcomes of 29 patients with AF and ESRD undergoing dialysis who underwent LAAO were compared to those without ESRD. The primary composite outcomes were stroke, systemic embolization, or death. Results: No difference in mean CHADS-VASc score was noted between patients with versus without ESRD (4.1 ± 1.8 vs. 4.6 ± 1.9, p = 0.453). After a mean follow-up of 38 ± 16 months, the composite endpoint was significantly higher in patients with ESRD (hazard ratio, 5.12 [1.4–18.6]; p = 0.013) than in those without ESRD after LAAO therapy. Mortality was also higher in patients with ESRD (hazard ratio, 6.6 [1.1–39.7]; p = 0.038). The stroke rate was numerically higher in patients with versus without ESRD, but the difference was not statistically significant (hazard ratio, 3.2 [0.6–17.7]; p = 0.183). Additionally, ESRD was associated with device-related thrombosis (odds ratio, 6.15; p = 0.047). Conclusion: Long-term outcomes of LAAO therapy may be less favorable in patients with AF undergoing dialysis, possibly because of the poor condition of patients with ESRD.

Background Implantation of the left atrial appendage occluder (LAAO) has been proven to prevent stroke effectively in patients with atrial fibrillation who cannot tolerate anticoagulants. Incomplete endothelization of LAAO may cause device‐related thrombus, and currently no good image modality exists to clearly see LAAO endothelialization. We aimed to use coronary optic coherence tomography (OCT) to visualize LAAO endothelialization. Methods and Results We enrolled 14 patients (72.8±9.4 years old) undergoing pulmonary vein isolation with a preexisting LAAO implanted more than 1 year ago (5 Watchman and 9 Amulet). After pulmonary vein isolation, we did OCT via steerable sheath and coronary guiding catheter to adjust OCT probe location and injected contrast medium to visualize the LAAO surface. In vitro testing was also performed to see the bare occluder. In vitro OCT showed the surface of the bare device as an interrupted granule pattern, which included the Watchman surface polytetrafluoroethylene membrane string, Amulet disc metal strut, and inner polytetrafluoroethylene membrane string. In the implanted Watchman, OCT showed endothelialization as a smooth surface layer with noninterrupted coarser granules. In the implanted Amulet, OCT showed endothelialization as thin (early) or thick (late) endothelialization layer covering struts with OCT shadows. Among patients with Watchman, 2 showed no, 2 early, and 1 complete endothelialization. Among patients with Amulet, 2 showed no, 3 early, and 4 late endothelialization. Conclusions We demonstrated the feasibility of OCT to visualize LAAO endothelization with high resolution. Further studies are needed to determine antithrombotic regimens if incomplete endothelization is detected. A new OCT catheter may be designed specifically for LAAO.

Abstract Background It is common to support cardiovascular function in critically ill patients with extracorporeal membrane oxygenation (ECMO). The purpose of this study was to identify patients receiving ECMO with a considerable risk of dying in hospital using machine learning algorithms. Methods A total of 1342 adult patients on ECMO support were randomly assigned to the training and test groups. The discriminatory power (DP) for predicting in-hospital mortality was tested using both random forest (RF) and logistic regression (LR) algorithms. Results Urine output on the first day of ECMO implantation was found to be one of the most predictive features that were related to in-hospital death in both RF and LR models. For those with oliguria, the hazard ratio for 1 year mortality was 1.445 (p

Abstract Background Ventricular premature complex (VPC) is a common arrhythmia in clinical practice. VPC could trigger ventricular tachycardia/fibrillation or VPC-induced cardiomyopathy in susceptible patients. Existing screening methods require prolonged monitoring and are limited by cost and low yield when the frequency of VPC is low. Twelve-lead electrocardiogram (ECG) is low cost and widely used. We aimed to identify patients with VPC during normal sinus rhythm (NSR) using artificial intelligence (AI) and machine learning-based ECG reading. Methods We developed AI-enabled ECG algorithm using a convolutional neural network (CNN) to detect the ECG signature of VPC presented during NSR using standard 12-lead ECGs. A total of 2515 ECG records from 398 patients with VPC were collected. Among them, only ECG records of NSR without VPC (1617 ECG records) were parsed. Results A total of 753 normal ECG records from 387 patients under NSR were used for comparison. Both image and time-series datasets were parsed for the training process by the CNN models. The computer architectures were optimized to select the best model for the training process. Both the single-input image model (InceptionV3, accuracy: 0.895, 95% confidence interval [CI] 0.683–0.937) and multi-input time-series model (ResNet50V2, accuracy: 0.880, 95% CI 0.646–0.943) yielded satisfactory results for VPC prediction, both of which were better than the single-input time-series model (ResNet50V2, accuracy: 0.840, 95% CI 0.629–0.952). Conclusions AI-enabled ECG acquired during NSR permits rapid identification at point of care of individuals with VPC and has the potential to predict VPC episodes automatically rather than traditional long-time monitoring.

Background Atrial fibrillation (AF) is associated with increasing risk of thromboembolic or ischemic stroke. The CHA2DS2‐VASc score is a well‐established predictor of AF stroke. Patients with AF have an increased risk of stroke if they have diabetes. Use of sodium‐glucose cotransporter‐2 inhibitor (SGLT2i) has been shown to be associated with favorable cardiovascular outcomes in patients with diabetes. It was unknown whether use of SGLT2i decreased stroke risk in patients with AF who have diabetes. Methods and Results A total of 9116 patients with AF and diabetes from the National Taiwan University historical cohort were longitudinally followed up for 5 years (January 2016–December 2020). The risk of stroke related to SGLT2i use was evaluated by Cox model, adjusting CHA2DS2‐VASc score in the propensity score–matched population with 474 SGLT2i users and 3235 nonusers. Adverse thromboembolic end points during follow‐up were defined as ischemic stroke. The mean age was 73.2±10.5 years, and 61% of patients were men. There were no significant differences of baseline characteristics between users and nonusers of SGLT2i, including CHA2DS2‐VASc score in the propensity score–matched population. The stroke rate was 3.4% (95% CI, 2.8–4.2) patient‐years in SGLT2i users and 4.3% (95% CI, 4.0–4.6) in nonusers (P=0.021). SGLT2i users had a 20% reduction of stroke (hazard ratio, 0.80 [95% CI, 0.64–0.99]; P=0.043) after adjustment for the CHA2DS2‐VASc score. Conclusions Use of SGLT2i was associated with a lower stroke risk in patients with diabetes and AF, and it may be considered to escalate SGLT2i to the first‐line treatment in patients with diabetes and AF.

Given that current cuffless blood pressure (BP) measurement technologies feature acceptable overall accuracy, this paper proposed a sufficiently accurate cuffless BP estimation method based on photoplethysmography (PPG) and electrocardiography (ECG) signals. This study used single-channel PPG and ECG signals to estimate heart rate (HR), diastolic BP (DBP), and systolic BP (SBP). A modified long-term recurrent convolutional network comprising a multi-scale convolution network and a long short-term memory (LSTM) network was used to develop a deep learning model for accurately estimating BP and HR. The PPG and ECG signal data of 1551 patients were obtained from the Data Sets-UCI Machine Learning Repository of the University of California, Irvine. The study dataset comprised ECG, PPG, and arterial BP (ABP) signals from the PhysioNet MIMIC II dataset. The original signals were processed by removing noise and artifacts. The aforementioned dataset contains 12,000 records in a hierarchical data format, with each record containing three signals, namely 125-Hz ECG signals from channel II (ECG lead II), 125-Hz PPG signals from the fingertip, and 125-Hz invasive ABP signals. To validate the stability and performance of the developed model, ten-fold cross-validation was conducted. The mean absolute error (MAE) (standard deviation (SD)) values of the developed model for predicting SBP, DBP, and HR were 2.24 mmHg (3.59 mmHg), 1.40 mmHg (2.56 mmHg), and 0.84 bpm (2.23 bpm), respectively. In addition, the estimated SBP and DBP values satisfied the standards of the British Hypertension Society and the Association for the Advancement of Medical Instrumentation. Compared with the methods proposed in other studies, the deep learning model developed in this study required a lower number of layers to provide accurate SBP, DBP, and HR estimations. The results of this study confirmed the effectiveness of the proposed deep learning architecture.

Background: Diastolic dysfunction (DD) has shown to be a hallmark pathological intermediate in the development of heart failure with preserved ejection fraction (HFpEF). We aim to establish age- and sex-stratified normal reference values of diastolic indices and to explore racial-differences. Methods: We explored age- and sex-related structural/functional alterations from 6023 healthy ethnic Asians (47.1 ± 10.9 years, 61.3% men) according to 2016 American Society of Echocardiography (ASE) diastolic dysfunction (DD) criteria. Racial comparisons were made using data from London Life Sciences Prospective Population (LOLIPOP) study. Results: Age- and sex-based normative ranges (including mean, median, 10% and 90% lower and upper reference values) were extracted from our large healthy population. In fully adjusted models, advanced age was independently associated with cardiac structural remodeling and worsened diastolic parameters including larger indexed LA volume (LAVi), lower e’, higher E/e’, and higher TR velocity; all p

Since December 2019, the outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly around the world. The severity of COVID-19 ranges from asymptomatic carriers to severe acute respiratory distress syndrome (ARDS). Accumulating evidence has shown that COVID-19 may be associated with multiple organ complications including cardiac injury, viral myositis and neurological deficits. Numerous laboratory biomarkers including lymphocytes, platelets, lactate dehydrogenase and creatine kinase (CK) have been associated with the prognostic outcomes of patients with COVID-19. However, dynamic correlations between levels of biomarkers and clinical course have not been studied.Herein, we report a 74-year-old female patient with severe COVID-19 which progressed to ARDS requiring intubation and mechanical ventilation. The laboratory findings showed lymphopenia, hypogammaglobulinemia, and elevated inflammatory biomarkers and CK. She received intensive therapy with hydroxychloroquine, lopinavir/ritonavir, and azithromycin with limited effects. Immunomodulatory treatments with high dose intravenous immunoglobulin and baricitinib were prescribed with satisfactory biochemical, radiographic and clinical recovery. We found an interesting correlation between serum CK elevation and inflammatory biomarkers, which reflected clinical improvement. This case demonstrates that inflammatory biomarkers, cytokines, and CK level correlated with disease severity and treatment response, and combined use of intravenous immunoglobulin and baricitinib is a potential treatment in patients with severe COVID-19.

Abstract Diabetes mellitus (DM) is a common comorbidity and risk factor for postoperative complications in head and neck (H&N) microsurgical reconstructions. Our study focused on the association between DM and individual complications regarding both surgical and medical aspects. A meta-analysis of English-language articles comparing a series of complications between DM and non-DM H&N free-flap recipients was performed by comprehensive meta-analysis (CMA). Twenty-seven articles presented 14,233 H&N free-flap reconstructions, and a subset of 2329 analyses including diabetic cases was included for final analysis. Total postoperative (RR = 1.194, p

Background: Left atrial (LA) size represents atrial fibrillation (AF) burden and has been shown to be a predictor for AF stroke. The CHA2DS2-VASc score is also a well-established predictor of AF stroke. It is unknown to cardiologists whether these two risk scores are correlated, whether both are independent prognostic predictors and complimentary to each other, or whether one of them is a major determinant of stroke risk for AF patients.Method: A total of 708 patients from the National Taiwan University Atrial Fibrillation Registry were longitudinally followed up for more than 15 years. Left atrial size was measured by M mode of echocardiography. Adverse thromboembolic endpoints during follow-up were defined as ischemic stroke or transient ischemic attack.Results: The mean age was 72.1 ± 12.9 years, with 53% men. Both LA size and CHA2DS2-VASc score were associated with the risk of stroke in univariate analyses. There was a weak but significant positive correlation between LA size and CHA2DS2-VASc score (r = 0.17, P < 0.0001). Patients with higher CHA2DS2-VASc scores had a higher mean LA size (P < 0.01 for trend). When combining LA size and CHA2DS2-VASc score in the multivariable Cox model, only CHA2DS2-VASc score remained statistically significant [HR 1.39 (1.20–1.63); P < 0.001].Conclusion: LA size is not an independent predictor of AF stroke, and calculation of CHA2DS2-VASc score may be an alternative to measurement of echocardiographic LA size when evaluating the risk of stroke for AF patients.

This study used photoplethysmography signals to classify hypertensive into no hypertension, prehypertension, stage I hypertension, and stage II hypertension. There are four deep learning models are compared in the study. The difficulties in the study are how to find the optimal parameters such as kernel, kernel size, and layers in less photoplethysmographyt (PPG) training data condition. PPG signals were used to train deep residual network convolutional neural network (ResNetCNN) and bidirectional long short-term memory (BILSTM) to determine the optimal operating parameters when each dataset consisted of 2100 data points. During the experiment, the proportion of training and testing datasets was 8:2. The model demonstrated an optimal classification accuracy of 76% when the testing dataset was used.

Background: Gut microbiome alterations might be considered a metabolic disorder. However, the relationship between the microbiome and acute myocardial infarction (AMI) has not been properly validated. Methods: The feces of 44 subjects (AMI: 19; control: 25) were collected for fecal genomic DNA extraction. The variable region V3–V4 of the 16S rRNA gene was sequenced using the Illumina MiSeq platform. The metabolite amounts were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways. Results: The bacteria were more enriched in the AMI group both in the observed operational taxonomic units (OTUs) and faith phylogenetic diversity (PD) (p-value = 0.01 and Selenomonadales were less enriched in the AMI group at the family, genus, and species levels (all linear discriminant analysis (LDA) scores > 2). Seleno-compounds were more abundant in the AMI group at the family, genus, and species levels (all LDA scores > 2). Conclusions: This is the first study to demonstrate the association of Selenomonadales and seleno-compounds with the occurrence of AMI. Our findings provide an opportunity to identify a novel approach to prevent and treat AMI.

Background: This 12-year study aimed to compare the longitudinal change in left ventricular diastolic dysfunction (LVDD) between healthy elderly, coronary artery disease (CAD), and hypertension (HTN) patients. Methods: From 2008 to 2020, 1476 patients were included, and 3181 echocardiography examinations were conducted. Finally, 130 participants (36 healthy elderly (79.39 ± 9.51 years old), 51 with CAD (68.31 ± 12.09 years old), and 43 with HTN (68.31 ± 12.09 years old)) with more than a 10-year follow-up period were included in the final analysis. Results: The change in diastolic function was different among these subjects according to the integrated score index (elderly vs. HTN, p = 0.01; CAD vs. HTN, p = 0.01), septal E/e′ ratio (elderly vs. HTN, p < 0.001; CAD vs. HTN, p = 0.01), lateral E/e′ ratio (elderly vs. HTN, p < 0.001; CAD vs. HTN, p < 0.001), and NYHA functional class (elderly vs. HTN, p = 0.03; CAD vs. HTN, p < 0.001). Additionally, per one-year increase in age, the integrated score index increased 0.2 in the healthy elderly, 0.15 in the CAD, and 0.06 in the HTN patients (all p < 0.05). Conclusion: Under aggressive treatment, diastolic function was relatively preserved in HTN subjects with aging in comparison with elderly and CAD subjects.

Background: Among various bio-informative molecules transferred by exosomes between cells, micro RNAs (miRNAs), which remain remarkably stable even after freeze-and-thaw cycles, are excellent candidates for potential biomarkers for coronary artery disease (CAD). Methods: Blood samples were collected from the coronary arteries of 214 patients diagnosed with three-vessel CAD and 140 without CAD. After precipitation extraction, the amounts of exosomes were found to decrease with increased age and three-vessel CAD. Next-generation sequencing was performed to further explore the possible relationship between exosomal miRNAs and CAD. Results: Eight exosomal miRNAs showed altered expression associated with CAD. The up-regulated miRNAs in CAD were miRNA-382-3p, miRNA-432-5p, miRNA-200a-3p, and miRNA-3613-3p. The down-regulated miRNAs were miRNA-125a-5p, miRNA-185-5p, miRNA-151a-3p, and miRNA-328-3p. Conclusion: We successfully demonstrated particular exosomal miRNAs that may serve as future biomarkers for CAD.

Background: The associations among chronic health conditions, ventricular geometric alterations or cardiac contractile mechanics in different phenotypes heart failure (HF) remain largely unexplored. Methods: We studied 438 consecutive hospitalized patients (mean age: 64.9 ± 16.6 years, 52.5% female) with or without clinical evidence of HF. We examined the associations among clinical co-morbidities, LV geometries and systolic mechanics in terms of global myocardial strains. Results: Increasing clinical co-morbidities was associated with greater LV mass, worse longitudinal deformations and higher proportion of admission with HF diagnosis, which was more pronounced in HFpEF (from 6.4% to 40.7%, X2 < 0.001). The independent association between co-morbidity burden and longitudinal functional decay remained unchanged after adjusting for age and sex for all admissions and in HFpEF (Coef: 0.82 & 0.71, SE: 0.13 & 0.21, both p≤0.001). By using co-morbidity scores, the area under receiver operating characteristic curves (AUROC) in identifying HFpEF was 0.71 (95% CI: 0.65 to 0.77), 0.64 (95% CI: 0.58 to 0.71) for HFrEF and 0.72 for both (95% CI: 0.67 to 0.77). Co-morbidity burden superimposed on LV mass index and LV filling pressure (E/E’) further expanded the AUROC significantly in diagnosing both types HF (c-statistics from 0.73 to 0.81, p for ΔAUROC: 0.0012). Conclusion: Chronic health conditions in the admission population were associated with unfavorable cardiac remodeling, impair cardiac contractile mechanics and further added significantly incremental value in HF diagnosis. Our data suggested the potentiality for better cardiac function by controlling baseline co-morbidities in hospitalized HF patients, especially HFpEF. Abbreviations: CAD: coronary artery disease; CKD: chronic kidney disease; DT: deceleration time; eGFR: Estimated glomerular filtration rate; HF: heart failure; IVRT: iso-volumic relaxation time; LV: left ventricular; LVEF: left ventricular ejection fraction; RWT: relative wall thickness; TDI: Tissue Doppler imaging

Summary: Several studies have shown the beneficial effect of renal denervation (RDN) in the treatment of ventricular arrhythmia, especially in the setting of heart failure (HF). However, the underlying mechanism of antiarrhythmic effect of RDN is unknown. Arrhythmogenic cardiac alternans, particularly spatially discordant repolarization alternans, characterized by simultaneous prolongation and shortening of action potential duration (APD) in different myocardial regions, is central to the genesis of ventricular fibrillation in HF. Whether RDN decreases the susceptibility to arrhythmogenic cardiac alternans in HF has never been addressed before. The authors used a rat model of post-myocardial infarction HF and dual voltage-calcium optical mapping to investigate whether RDN could attenuate arrhythmogenic cardiac alternans that predisposes to ventricular arrhythmias, as well as the hemodynamic effect of RDN in HF. The HF rats had increased body weights, dilated hearts, and lower blood pressure. The HF rats also had longer ventricular APDs and a delay in the decay of the calcium transient, typical electrophysiological features of human HF. Susceptibility to calcium transient alternans, APD alternans, and spatially discordant APD alternans was increased in the HF hearts. RDN significantly attenuated a delay in the decay of the calcium transient, calcium transient and APD alternans, and importantly, the discordant APD alternans, and thereby decreased the incidence of induced ventricular arrhythmia in HF. RDN did not further decrease blood pressure in HF rats. In conclusion, RDN improves calcium cycling and prevents spatially discordant APD alternans and ventricular arrhythmia in HF. RDN does not aggravate hemodynamics in HF. Key Words: alternans, arrhythmia mechanism, heart failure, renal denervation

Tsai et al. here utilize a multi-stage genome-wide association study in Taiwanese population to show a copy number variation in the intron of potassium interacting channel 1 gene (KCNIP1) to be strongly associated with atrial fibrillation. The study also examines the functionality of KCNIP1 in heart electrophysiological function using cultured myocytes and zebrafish.

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson's correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.

Mechanics in the human body are required for normal cell function at a molecular level. It is now clear that mechanical stimulations play significant roles in cell growth, differentiation, and migration in normal and diseased cells. Recent studies have led to the discovery that normal and cancer cells have different mechanosensing properties. Here, we discuss the application and the physiological and pathological meaning of mechanical stimulations. To reveal the optimal conditions for mimicking an in vivo microenvironment, we must, therefore, discern the mechanotransduction occurring in cells.

Atrial fibrillation (AF) is a common cardiac arrhythmia and is one of the major causes of ischemic stroke. In addition to the clinical factors such as CHADS2 or CHADS2-VASC score, the impact of genetic factors on the risk of thromboembolic stroke in patients with AF has been largely unknown. Single-nucleotide polymorphisms in several genomic regions have been found to be associated with AF. However, these loci do not contribute to all the genetic risks of AF or AF related thromboembolic risks, suggesting that there are other genetic factors or variants not yet discovered. In the human genome, copy number variations (CNVs) could also contribute to disease susceptibility. In the present study, we sought to identify CNVs determining the AF-related thromboembolic risk. Using a genome-wide approach in 109 patients with AF and thromboembolic stroke and 14,666 controls from the Taiwanese general population (Taiwan Biobank), we first identified deletions in chromosomal regions 1p36.32-1p36.33, 5p15.33, 8q24.3 and 19p13.3 and amplifications in 14q11.2 that were significantly associated with AF-related stroke in the Taiwanese population. In these regions, 148 genes were involved, including several microRNAs and long non-recoding RNAs. Using a pathway analysis, we found deletions in GNB1, PRKCZ, and GNG7 genes related to the alpha-adrenergic receptor signaling pathway that play a major role in determining the risk of an AF-related stroke. In conclusion, CNVs may be genetic predictors of a risk of a thromboembolic stroke for patients with AF, possibly pointing to an impaired alpha-adrenergic signaling pathway in the mechanism of AF-related thromboembolism.

Lower extremities varicose veins (VV) are among the most easily recognized venous abnormalities. The genetic mechanism of VV is largely unknown. In this study, we sought to explore the global expressional change of VV and identify novel genes that might play a role in VV. We used next-generation ribonucleic acid (RNA) sequence (RNA seq) technology to study the global messenger RNA expressional change in the venous samples of five diseased and five control patients. We identified several differentially expressed genes, which were further confirmed by conventional reverse transcription polymerase chain reaction (RT-PCR). Using these significant genes we performed in silico pathway analyses and found distinct transcriptional networks, such as angiogenesis, cell adhesion, vascular injury, and carbohydrate metabolisms that might be involved in the mechanism of VV. Among these significant genes, we also found hyaluronan synthases 2 gene (HAS2) played a pivotal role and governed all these pathways. We further confirmed that HAS2 expression was decreased in the venous samples of patients with VV. Finally, we used a zebrafish model with fluorescence emitting vasculature and red blood cells to see the morphological changes of the venous system and blood flow. We found that HAS2 knockdown in zebrafish resulted in dilated venous structural with static venous flow. HAS2 may modulate the transcriptional networks of angiogenesis, cell adhesion, vascular injury, and carbohydrate metabolisms in venous tissues and downregulation of HAS2 may underlie the mechanism of VV.

The dynamics of a living body enables organs to experience mechanical stimulation at cellular level. The human cardiomyocytes cell line provides a source for simulating heart dynamics; however, a limited understanding of the mechanical stimulation effect on them has restricted potential applications. Here, we investigated the effect of mechanical stimulation on the cardiac function-associated protein expressions in human cardiomyocytes. Human cardiomyocyte cell line AC16 was subjected to different stresses: 5% mild and 25% aggressive, at 1 Hz for 24 h. The stretched cardiomyocytes showed down-regulated Piezo1, phosphorylated-Ak transforming serine473 (P-AKTS473), and phosphorylated-glycogen synthase kinase-3 beta serine9 P-GSK3βS9 compared to no stretch. In addition, the stretched cardiomyocytes showed increased low-density lipoprotein receptor-related protein 6 (LRP6), and phosphorylated-c-Jun N-terminal kinase threonine183/tyrosine185 (P-JNKT183/Y185). When Piezo inhibitor was added to the cells, the LRP6, and P-JNKT183/Y185 were further increased under 25%, but not 5%, suggesting that higher mechanical stress further activated the wingless integrated-(Wnt)-related signaling pathway when Piezo1 was inhibited. Supporting this idea, when Piezo1 was inhibited, the expression of phosphorylated-endothelial nitric oxide synthase serine1177 (P-eNOSS1177) and release of calcium ions were reduced under 25% compared to 5%. These studies demonstrate that cyclic mechanical stimulation affects cardiac function-associated protein expressions, and Piezo1 plays a role in the protein regulation.

This study aimed to apply the Taguchi optimization technique to determine the process conditions for producing synthetic lightweight aggregate (LWA) by incorporating tile grinding sludge powder with reservoir sediments. An orthogonal array L16(45) was adopted, which consisted of five controllable four-level factors (i.e., sludge content, preheat temperature, preheat time, sintering temperature, and sintering time). Moreover, the analysis of variance method was used to explore the effects of the experimental factors on the particle density, water absorption, bloating ratio, and loss on ignition of the produced LWA. Overall, the produced aggregates had particle densities ranging from 0.43 to 2.1 g/cm3 and water absorption ranging from 0.6% to 13.4%. These values are comparable to the requirements for ordinary and high-performance LWAs. The results indicated that it is considerably feasible to produce high-performance LWA by incorporating tile grinding sludge with reservoir sediments.

Amiodarone-related pneumonitis is a potentially limiting factor for amiodarone usage. However, it is believed that amiodarone-related pneumonitis is unlikely to occur during low-dose and short courses of therapy. We report three patients who received low-dose amiodarone, 200 mg/day, for an average of 6.6 months and who developed amiodarone-related pneumonitis. All patients were male with age of 75, 93 and 85, respectively, and had the habit of cigarette smoking. The initial presentation was dyspnea without symptoms and signs of heart failure. Their chest radiographs showed diffuse interstitial pneumonitis pattern and chest computed tomography scan also confirmed interstitial pneumonitis. Treatment included cessation of amiodarone and corticosteroid usage. All patients improved symptomatically by early detection and early treatment. This case report implies that old age and possible pre-existing pulmonary abnormalities caused by smoking could be associated with amiodarone-related pulmonary toxicity. Clinicians must remain alert to detect amiodarone-related pneumonitis even under low dosage and short duration of amiodarone usage. Immediate withdrawal of amiodarone and prompt steroid therapy will ensure full recovery.

We propose a novel integrated score index, which could be used to quantify and grade left ventricular (LV) diastolic function.We enrolled 629 participants [393 healthy subjects, 145 with hypertension (HTN), 24 with hypertrophic cardiomyopathy (HCM), and 67 with coronary artery disease (CAD)]. This score index was with a score of 1 for an E/A ratio < 1, a score of 1 for a septal e'/a' ratio ≤ 0.8, a score of 2 for a lateral e'/a' ratio ≤ 1, a score of 2 for a septal E/e' ratio ≥10-15, a score of 3 for a lateral E/e' ratio ≥8-15, and a score of 1 for a deceleration time >240 ms. The sum of each score was considered as the final value in this scoring method (either a septal or a lateral E/e' ratio > 15 was given a total score of 10, regardless of the other measurements).After analysis, the AUROC of this integrated score index for predicting any diastolic dysfunction (discriminated by the American Society of Echocardiography guidelines) was 0.962, and the AUROC of the method from the logistic regression was 0.970. The mean values of the score index for the groups were 3.81 ± 0.12 in healthy, 6.48 ± 0.19 in HTN, 7.35 ± 0.46 in HCM, and 6.62 ± 0.29 in CAD. Using the score index, the healthy subjects obtained lower scores compared with those of HTN (p = 0.00), HCM (p = 0.00), and CAD (p = 0.00). Therefore, this score index could discriminate patients with diseases with impaired diastolic function from the healthy subjects when the total sum of the score was equal to or greater than 4.If the presently used methods cannot allow the clear diagnosis of LV diastolic dysfunction, this integrated score index might be helpful for discriminating diseases with impaired diastolic function.

Although Amiodarone, a class III antiarrhythmic drug, inhibits zebrafish cardiac valve formation, the detailed molecular pathway is still unclear. Here, we proved that Amiodarone acts as an upstream regulator, stimulating similar to versican b (s-vcanb) overexpression at zebrafish embryonic heart and promoting cdh-5 overexpression by inhibiting snail1b at atrioventricular canal (AVC), thus blocking invagination of endocardial cells and, as a result, preventing the formation of cardiac valves. A closer investigation showed that an intricate set of signaling events ultimately caused the up-regulation of cdh5. In particular, we investigated the role of EGFR signaling and the activity of Gsk3b. It was found that knockdown of EGFR signaling resulted in phenotypes similar to those of Amiodarone-treated embryos. Since the reduced phosphorylation of EGFR was rescued by knockdown of s-vcanb, it was concluded that the inhibition of EGFR activity by Amiodarone is s-vcanb-dependent. Moreover, the activity of Gsk3b, a downstream effector of EGFR, was greatly increased in both Amiodarone-treated embryos and EGFR-inhibited embryos. Therefore, it was concluded that reduced EGFR signaling induced by Amiodarone treatment results in the inhibition of Snail functions through increased Gsk3b activity, which, in turn, reduces snail1b expression, leading to the up-regulation the cdh5 at the AVC, finally resulting in defective formation of valves. This signaling cascade implicates the EGFR/Gsk3b/Snail axis as the molecular basis for the inhibition of cardiac valve formation by Amiodarone.

BACKGROUND: Three dimensional (3D) echocardiography-derived measurements of myocardial deformation and twist have recently advanced as novel clinical tools. However, with the exception of left ventricular ejection fraction and mass quantifications in hypertension and heart failure populations, the prognostic value of such imaging techniques remains largely unexplored. METHODS: We studied 200 subjects (mean age: 60.2±16 years, 54% female, female n = 107) with known hypertension (n = 51), diastolic heart failure (n = 61), or systolic heart failure (n = 30), recruited from heart failure outpatient clinics. Fifty-eight healthy volunteers were used as a control group. All participants underwent 3D-based myocardial deformation and twist analysis (Artida, Toshiba Medical Systems, Tokyo, Japan). We further investigated associations between these measures and brain natriuretic peptide levels and clinical outcomes. RESULTS: The global 3D strain measurements of the healthy, hypertension, diastolic heart failure, and systolic heart failure groups were 28.03%, 24.43%, 19.70%, and 11.95%, respectively (all p