Background:Sustained ventricular tachycardia (VT) is a major cause of sudden cardiac death in structural heart disease (SHD). Risk stratification based on left ventricular ejection fraction (LVEF) remains suboptimal. This study aimed to develop an exploratory model integrating late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) scar characteristics with computational VT simulation to discriminate sustained VT, compared against LVEF. Methods:In this single-centre retrospective study, consecutive patients with suspected SHD who underwent LGE-CMR were enrolled. Patients with LGE-positive underwent quantitative scar analysis, personalized digital heart-twin reconstruction, and virtual electrophysiological simulation. Results:Among 82 patients (mean age 59.1 years; 82.9% male), 15 experienced sustained VT. Lower LVEF was associated with sustained VT (P = 0.008; C-statistic: 0.730), as was visual LGE positivity (P = 0.023; C-statistic: 0.634). Among LGE-positive patients, those with sustained VT had a larger core scar [10.0 [5.9, 14.8]% vs. 2.2 [1.1, 4.7]%; P < 0.001], larger grey zone [14.0 [10.9, 14.7]% vs. 5.7 [2.3, 9.2]%; P < 0.001], higher VT inducibility [50.0 [22.9, 66.9]% vs. 0 (0, 21.1)%; P < 0.001], and a greater number of inducible VT circuits [2 [2, 4] vs. 0 [0, 2]; P < 0.001]. An integrated LGE-VTsim index, derived from these four parameters, effectively discriminated sustained VT (C-statistic: 0.816) and remained independently associated with sustained VT after adjusting for LVEF (OR: 1.029; 95% CI: 1.008-1.051; P = 0.007). Conclusion:The LGE-VTsim index, integrating quantitative LGE-CMR scar assessment with computational simulation, represents a promising exploratory parameter in identifying patients at risk of sustained VT in SHD, beyond LVEF.

BackgroundNew-onset atrial fibrillation (NOAF) is the most commonly encountered arrhythmia during the course of acute myocardial infarction (AMI) and is independently associated with a worse prognosis.AimsWe aimed to validate the discriminatory performance of cancer antigen-125 (CA-125) in predicting post-AMI NOAF in the Chinese population.MethodsA total of 488 consecutive patients with AMI from 1 January 2020 to 1 January 2022 without a previous history of AF were enrolled in this study. Risk factors for post-AMI NOAF were determined using univariable and multivariable logistic regression analyses. Receiver operating characteristic (ROC) curve analyses were used to evaluate the discrimination performance of different parameters and score models. Area under the curve (AUCs) were compared using Z tests.ResultsIn total, 48 (9.84%) patients developed post-AMI NOAF during hospitalization. The NOAF group was older and had a higher Killip class, B-type natriuretic peptide level, CA-125 level, left atrial diameter, left ventricular end-systolic diameter, CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years [2 points], Diabetes mellitus, Stroke/transient ischemic attack/thromboembolism history [2 points], Vascular disease, Age 65–74 years, Sex category [female]) score, Global Registry of Acute Coronary Events (GRACE) risk score (RS), and in-hospital mortality, and a lower low-density lipoprotein level, left ventricular ejection fraction, and initial β-receptor blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use (P < 0.05 vs. the no-NOAF group for all measures). In the multivariate regression analyses, CA-125 remained an independent risk factor for post-AMI NOAF in different models. In the ROC curve analyses, CA-125 (AUC = 0.753, 95% CI: 0.665–0.84, P < 0.001), GRACE RS (AUC = 0.701, 95% CI: 0.593–0.809, P = 0.001), and CHA2DS2-VASc score (AUC = 0.644, 95% CI: 0.532–0.757, P = 0.014) were valid tools to predict post-AMI NOAF. After Z tests, the discriminatory performance of CA-125 was significantly higher than that of the CHA2DS2-VASc score (P = 0.038), but not statistically significantly higher than that of the GRACE RS (P = 0.353).ConclusionAn elevated plasma CA-125 level was independently associated with NOAF after AMI, with high discriminatory performance.

Abstract Background Atrial fibrillation (AF) is associated with circulating inflammation. Short-chain fatty acids (SCFAs) derived from gut microbiota (GM) regulate leukocyte function and inhibit the release of inflammatory cytokines, which are partly mediated by the G-protein-coupled receptor 43 (GPR43) signaling. This study aimed to investigate the expression of GPR43/NOD-like receptors family pyrin domain containing 3 (NLRP3) in leukocytes and the interaction with intestinal SCFAs levels in AF patients. Methods Expressions of GPR43 and NLRP3 mRNA in peripheral blood leukocytes from 23 AF patients and 25 non-AF controls were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Expressions of leukocyte GPR43 and NLRP3 protein were evaluated by western blot analysis. The levels of plasma IL-1β were measured by enzyme-linked immunosorbent assay (ELISA). The fecal SCFAs levels based on GC/MS metabolome of corresponding 21 controls and 14 AF patients were acquired from our published dataset. To evaluate the expression of NLRP3 and GPR43 and the release of IL-1β, human THP-1 cells were stimulated with or without SCFAs (acetate, propionate, and butyrate), lipopolysaccharide (LPS), and nigericin in vitro, respectively. Results Compared to the controls, the mRNA expression in peripheral leukocytes was significantly reduced in AF patients (P = 0.011) coupled with the increase in downstream leukocyte NLRP3 mRNA expression (P = 0.007) and plasma IL-1β levels (P < 0.001), consistent with changes in GPR43 and NLRP3 protein expression. Furthermore, leukocyte GPR43 mRNA levels were positively correlated with fecal GM-derived acetic acid (P = 0.046) and negatively correlated with NLRP3 mRNA expression (P = 0.024). In contrast to the negative correlation between left atrial diameter (LAD) and GPR43 (P = 0.008), LAD was positively correlated with the leukocyte NLRP3 mRNA levels (P = 0.024). Subsequent mediation analysis showed that 68.88% of the total effect of intestinal acetic acid on AF might be mediated by leukocyte GPR43/NLRP3. The constructed GPR43–NLRP3 score might have a predictive potential for AF detection (AUC = 0.81, P < 0.001). Moreover, SCFAs treatment increased GPR43 expression and remarkably reduced LPS/nigericin-induced NLRP3 expression and IL-1β release in human THP-1 cells in vitro. Conclusions Disrupted interactions between GPR43 and NLRP3 expression in peripheral blood leukocytes, associated with reduced intestinal GM-derived SCFAs, especially acetic acid, may be involved in AF development and left atrial enlargement by enhancing circulating inflammation.

This study aimed to investigate the role of the gut microbiota (GM)-bile acid (BA)-fibroblast growth factor (FGF) 19 axis in patients with atrial fibrillation (AF). Gut bacterial metabolisms of BAs were determined in an AF metagenomic dataset. The composition of faecal BAs pools was characterized by targeted metabolomics in an independent AF cross-sectional cohort. Circulating levels of FGF19 were measured by ELISA. In vitro cell experiments were conducted to validate the regulatory role of FGF19 in atrial cardiomyocytes stimulated with palmitic acid. First, metagenomic profiling revealed that gut microbial biotransformation from primary to secondary BAs was dysregulated in AF patients. Second, the proportion of secondary BAs decreased in the faeces of patients with AF. Also, eight BAs were identified as AF-associated BAs, including seven AF-enriched BAs (ursodeoxycholic acid, chenodeoxycholic acid, etc.), and AF-decreased dehydrolithocholic acid. Third, reduced levels of circulating FGF19 were observed in patients with AF. Subsequently, FGF19 was found to protect against palmitic acid-induced lipid accumulation and dysregulated signalling in atrial cardiomyocytes, including attenuated phosphorylation of YAP and Ca2+ /calmodulin-dependent protein kinases II and secretion of interleukin-1β, mediated via peroxisome proliferator-activated receptor α. Our data found decreased levels of secondary BAs and circulating FGF19, resulting in the impaired protective function of FGF19 against lipid accumulation in atrial cardiomyocytes.

Emerging evidence suggests an association of dysbiotic gut microbiota (GM) with atrial fibrillation (AF). The current study aimed to determine whether aberrant GM promotes AF development. A fecal microbiota transplantation (FMT) mouse model demonstrated that dysbiotic GM is sufficient to enhance AF susceptibility assessed by transesophageal burst pacing. Compared with recipients transplanted with GM obtained from healthy subjects (FMT-CH), the prolonged P wave duration and an enlarging tendency for the left atrium were detected in recipients transplanted with AF GM (FMT-AF). Meanwhile, the disrupted localizations of connexin 43 and N-cadherin and increased expression levels of phospho-CaMKII and phospho-RyR2, were observed in the atrium of FMT-AF, which indicated aggravated electrical remodeling caused by the altered gut flora. Specifically, exacerbated fibrosis disarray, collagen deposition, α-SMA expression, and inflammation in the atrium were also confirmed to be transmissible by the GM. Furthermore, deteriorated intestinal epithelial barrier and intestinal permeability, accompanied by disturbing metabolomic features in both feces and plasma, especially decreased linoleic acid (LA), were identified in FMT-AF mice. Subsequently, the anti-inflammatory role of LA among the imbalanced SIRT1 signaling discovered in the atrium of FMT-AF was confirmed in mouse HL-1 cells treated with LPS/nigericin, LA, and SIRT1 knockdown. This study provides preliminary insights into the causal role of aberrant GM in the pathophysiology of AF, suggesting the GM-intestinal barrier-atrium axis might participate in the vulnerable substrates for AF development, and the GM could be utilized as an environmental target in AF management.

目的 总结脉压差增大患者的血清代谢组特征.方法 本研究选取2014年9月至2015年11月自开滦医院(课题合作单位)纳入的脉压差增大受试者21例(脉压差≥60 mmHg),脉压差正常者103例(脉压差<60 mmHg).通过队列人群血清样本进行的液相色谱-质谱检测,分析研究组和对照组人群的血清中代谢物的组成,揭示血液循环中的代谢物在脉压差高患者中的改变情况.结果 临床指标显示,与脉压差正常的对照组人群比较,脉压差高组受试者血糖水平较高[6.01(5.58,6.78)mmHg比5.36(4.98,5.84)mmHg,P<0.0001],肾功能受损[73.00(66.00,98.11)μmol/L比70.00(60.00,78.25)μmol/L,P=0.019];血脂,包括低密度脂蛋白[2.93(2.64,3.25)mmol/L比2.41(2.03,2.86)mmol/L,P=0.004]和高密度脂蛋白[1.40(1.24,1.71)mmol/L比1.23(1.06,1.35)mmol/L,P=0.001]紊乱明显.在正离子和负离子模式下的代谢组数据表明,脉压差高组与对照组人群的血清代谢组特征经PLS-DA和OPLS-DA聚类分析可显著区分.PLS-DA在负离子模式下,第一主成分的可解释度间差异为0.047;正离子模式下,第一主成分的可解释度间差异为0.0345.在脉压差高组中,乙酸、丙酮醛、2-酮丁酸等显著富集;丙酮酸、L-乳酸、马来酸等明显减少.此外,观察到差异代谢物之间呈现较为复杂的协同或互斥关系,如乙酸与D-葡萄糖、丙酮醛、2-羟基己二酸等呈正相关;L-谷氨酸与D-葡萄糖、丙酮醛、2-羟基己二酸等呈负相关.血脂、血糖、尿酸、血红蛋白、性别等临床代谢性指标与戊二酸、衣糠酸、棕榈酸、丙酮酸以及D-葡萄糖、月桂酸等差异代谢物呈显著相关.结论 脉压差增大患者的血清代谢组的结构和组成呈现病理性改变,患者肠道微生物的改变可能参与脉压差增大的病理生理过程.

目的 评价脉压差较大患者的粪便代谢组特征.方法 纳入河北省唐山开滦集团2014年5月至2016年5月共61例患者,脉压差高患者12例(脉压差≥60mmHg)为研究组,脉压差正常者49例(脉压差＜60mmHg)为对照组.通过液相色谱-质谱检测人群的粪便本,分析脉压差高组患者和脉压差正常人群的肠道中代谢物的组成,揭示肠道菌群代谢物在脉压差较大患者中的变化情况.结果 在正离子和负离子检测模式下,经PLS-DA和OPLS-DA聚类分析,研究组受试者的粪便代谢组特征可显著区分于对照组.油酸和胆碱显著富集在脉压差高组中;丙甲羟戊酸、二同-γ-亚麻酸、白三烯B4、前列腺素E2、前列腺素E1、脱氧胆酸、哌啶、5-戊二胺、烟酸、1-蛋氨酸、1-甲基黄嘌吟、n-硬脂酰谷氨酸、齐墩果酸等则明显减少.结论 脉压差较大的患者粪便代谢组的结构特征和代谢物组成显著改变.

Background: The optimal revascularization strategy for non-left anterior descending coronary artery Aims: This study aimed to compare the outcomes of the drug-coated balloon (DCB) and drug-eluting stent (DES) strategies in patients with non-small non-LAD lesions undergoing one-stop HCR. Methods: A total of 141 consecutive patients with multivessel coronary artery disease (MVCAD) undergoing one-stop HCR between June 1, 2018 and March 1, 2022 were retrospectively included in this study. In-hospital outcomes and mid-term major adverse cardiovascular and cerebrovascular events (MACCE) were observed. Kaplan-Meier curve analysis was used to evaluate the MACCE-free survival rate. The Cox proportional hazard model was used to identify risk factors of mid-term MACCE. Results: Thirty-eight and 103 patients received only DCB or DES therapy, respectively, in this study. There were no significant differences in demographic characteristics and laboratory parameters between the two groups. The in-hospital MACCE rate in the DES group was numerically higher than that in the DCB group (9.7% vs. 5.3%, respectively), but the difference was not statistically significant (P = 0.4). The incidence of MACCE after patients'discharge was significantly higher in the DES group (22% vs. 5.3%, respectively, P = 0.02) during a median follow-up of 20 months. In multivariable Cox proportional hazard analysis, DCB therapy was independently associated with reduced risk of midterm MACCE (hazard ratio, 0.21; 95% confidence interval, 0.06-0.91; P = 0.04). Conclusion: For patients with MVCAD undergoing one-stop HCR, DCB therapy may be the optimal revascularization strategy for non-small non-LAD coronary artery lesions with a significantly lower rate of mid-term MACCE.

Percutaneous coronary intervention (PCI) treatment significantly improves outcomes after acute myocardial infarction (AMI). It remains unclear whether the benefits of PCI exist in patients with end-stage renal disease (ESRD) and non-ST-segment elevation myocardial infarction (NSTEMI). The present study was designed to investigate the effects of PCI on the short- and long-term prognosis of patients with ESRD and NSTEMI. We conducted a retrospective study from 1 January 2015 to 1 January 2020, which includes 148 consecutive patients with ESRD and NSTEMI. All patients were estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2 and had received regular hemodialysis treatment before hospitalization. Logistic regression analyses were used to identify the risk factors for in-hospital mortality. Cox proportional hazard model was used to identify independent predictors of 1-year major adverse cardiac events (MACE). In this study, 62 patients received PCI treatment. Univariable logistic regression analysis showed that PCI treatment was associated with the trend of reduction in the risk of in-hospital mortality (11.3% vs 43%, P = 0.022), but was not independently related to lower in-hospital mortality risk after multivariable logistic regression analysis (P = 0.131). After a 1-year follow-up, Kaplan–Meier survival analysis demonstrated that MACE rate was significantly lower in patients with ESRD and NSTEMI who had received PCI treatment during hospitalization (P < 0.001). After multivariate Cox proportional hazard analysis, no PCI treatment was independently associated with 1-year MACE (hazard ratios 3.217, 95% CI 2.03–8.489, P = 0.003). PCI treatment during hospitalization is associated with reduced 1-year MACE in patients with ESRD and NSTEMI, which suggests that more aggressive therapies may be beneficial for this special higher risk population.

Background: In response to the outbreak of coronavirus disease 2019 (COVID-19) worldwide, inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are implemented. Dysbiosic gut microbiota is implicated in the COVID-19 patients. Whereas, how intestinal microbiota are affected by vaccination remains elusive, and it is important to investigate the microbial shifts during vaccines treatment. Methods: In the present study, we assessed the gut microbial composition in healthy adults, and performed comparison before and post an inactivated SARS-CoV-2 vaccine candidate, BBIBP-CorV vaccination. Results: Microbial diversity in shannon, pielou evenness, simpson and invsimpson index was remarkably suppressed by vaccination. Ruminococcus and Actinomyces were observed to be strikingly deficient, and Faecalibacterium was dramatically augmented after BBIBP-CorV treatment. Potential functional profiles of gut microbiome in amino acid metabolism, lipid biosynthesis proteins and steroid biosynthesis were remarkably increased, while the capacity in renin-angiotensin system was remarkably decreased following vaccines. Conclusions: Our study suggests that inactivated BBIBP-CorV against SARS-CoV-2 could elicit modulations on gut microbial composition and functions, which might favor host immune response and protect from COVID-19.

Background Nerve injury-induced protein 1 (Ninj1) is elevated in various inflammatory diseases. The soluble form of Ninj1 yield by matrix metalloproteinase cleavage is a secreted protein and inhibits cell adhesion and inflammation. However, the role of plasma Ninj1 in atrial fibrillation (AF) has not been reported. The present study aimed to investigate the correlation between plasma Ninj1 levels and AF. Methods A total of 96 AF patients [age 66.00 (60.00, 72.00) years, male 56 (58.33%)] and 51 controls without AF [age 65.00 (55.00, 68.00) years, male 21 (41.18%)] were enrolled in this study. Plasma Ninj1 concentrations were detected using enzyme-linked immunosorbent assay. Also, the clinical characteristics, left atrial volume index (LAVI), CHA2DS2-VASc score, and HAS-BLED score were evaluated. Results Plasma Ninj1 levels were significantly higher in patients with AF than in controls ( P < 0.001). Plasma Ninj1 levels were positively correlated with LAVI ( P = 0.019) and CHA2DS2-VASc score ( P = 0.024). Logistic regression analysis confirmed that the Ninj1 plasma levels were associated with AF ( P = 0.009). The receiver operating characteristic analysis showed that plasma Ninj1 had a predictive value for AF ( P < 0.001). Conclusions Plasma Ninj1 levels were elevated in patients with AF, associated with left atrial enlargement and thromboembolic risk in AF.

Background: Expression of nerve injury-induced protein 1 (Ninj1) is associated with several inflammatory disease. The soluble Ninj1 is an antiatherogenic protein. However, the role of plasma Ninj1 levels in patients with coronary artery disease (CAD) and its correlation with the severity of the disease remains unknown. This study investigated the association between plasma Ninj1 levels and the severity of coronary artery stenosis in patients with CAD. Methods: A total of 207 subjects were recruited in this study. Blood samples were obtained to assess plasma Ninj1 level using enzyme-linked immunosorbent assay. The SYNTAX score calculated from baseline coronary angiography results was used to evaluate the severity of coronary artery stenosis. The least absolute shrinkage and selection operator (LASSO) regression analysis was performed to select the predictive factors. Then, a nomogram based on Ninj1 was constructed to predict the probability of CAD. Results: Patients with CAD had significantly higher plasma Ninj1 than those without CAD (P < 0.001). A positive correlation was established between the Ninj1 levels and SYNTAX score (R = 0.352, P < 0.001). The multivariate logistical regression analysis indicated that plasma Ninj1 (P = 0.024) was an independent predictor of CAD occurrence after adjustment for clinical risk factors. The nomogram based on plasma Ninj1 level demonstrated good calibration and discrimination with the area under the curve 0.814. Conclusions: Plasma Ninj1 levels are increased in patients with CAD. Elevated levels of plasma Ninj1 are associated with CAD and the severity of coronary stenosis. A nomogram based on plasma Ninj1 and sectional clinical characteristics exerted a predictive potential for CAD.

This study examined the effect of sleep disturbance on gut microbiota (GM), atrial substrate, and atrial fibrillation (AF) inducibility. C57BL/6 mice were subjected to six weeks of sleep deprivation (SD) using the method of modified multiple-platform. Transesophageal burst pacing was performed to evaluate AF inducibility. Feces, plasma, and an atrium were collected and analyzed by 16s rRNA sequencing, liquid chromatography–mass spectrometry (LC-MS)-based metabolome, histological studies, and transcriptome. Higher AF inducibility (2/30 of control vs. 15/30 of SD, p = 0.001) and longer AF duration (p < 0.001), concomitant with aggravated fibrosis, collagen, and lipid accumulation, were seen in the SD mice compared to control mice. Meanwhile, elevated alpha diversity, higher abundance of Flavonifractor, Ruminococcus, and Alloprevotella, as well as imbalanced functional pathways, were observed in the gut of SD mice. Moreover, the global patterns for the plasma metabolome were altered, e.g., the decreased butanoate metabolism intermediates in SD mice. In addition, disrupted metabolic homeostasis in the SD atrium, such as fatty acid metabolism, was analyzed by the transcriptome. These results demonstrated that the crosstalk between GM and atrial metabolism might be a promising target for SD-mediated AF susceptibility.

Background. In our previous studies, we found a disordered taxonomic composition and function of gut microbiota (GM) in atrial fibrillation (AF) patients. However, direct evidence about the association between dysbiotic microbiota and thromboembolic risk in AF is lacking. Aims. In this study, we analyzed the interaction of GM and related functional patterns in AF with different CHA2DS2-VASc scores to assess its potential as a biomarker for predicting stroke risk. Patients and Methods. The CHA2DS2-VASc score was used for thromboembolic risk stratification in AF according to American Heart Association (AHA) guidelines. We investigated the taxonomic and functional annotation of GM based on metagenomic data from 50 AF patients (32 with high thromboembolic risk (CHA2DS2-VASc score ≥2 (males) or CHA2DS2-VASc score ≥3 (females)) and 18 individuals with low thromboembolic risk (CHA2DS2-VASc score <2 (males) or CHA2DS2-VASc score <3 (females))). Results. The gut microbial diversity, composition, and function in AF were different in high and low CHA2DS2-VASc score groups. In high thromboembolic risk group, the abundance of Prevotella, Lachnospiraceae, and Eubacterium rectale, related to the production of short-chain fatty acids and anti-inflammatory were reduced (all P < 0.05 ). Furthermore, annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG), a database of genes and genomes, the KEGG orthology-based scoring approach exhibited a significant association with thromboembolic risk in AF patients. Conclusions. Imbalance of GM and microbial dysfunction are involved in aggravated thromboembolic risk of AF.

Radial artery occlusion (RAO) is still a major complication of coronary catheterization (CC) via transradial access (TRA). Recently, coronary angiography (CAG) and percutaneous coronary intervention (PCI) through distal transradial access (dTRA) have been proven to be safe and feasible, but RAO recanalization and complete CC via dTRA have been rarely reported. Twenty-nine consecutive patients with RAO were enrolled in the present study. RAO was first confirmed by ultrasonography and after puncture of the distal radial artery (RA) in the anatomical snuffbox; cannula angiography was conducted to confirm total RAO. With the exception of two patients, we successfully recanalized the occluded RA in 27 patients. After RAO recanalization, subsequent CAG and PCI were successful, and no complications occurred. RAO recanalization and complete coronary catheterization via dTRA are safe and feasible.

Disordered gut microbiota (GM) as the co-contributor of atrial fibrillation (AF) and hypertension (HTN) might be associated with AF risk in HTN. This study aimed to explore the altered GM community and metabolic patterns between 27 HTN patients with AF (HTN-AF) and 27 non-AF HTN patients through fecal metagenomic and serum metabolomic analysis. Compared to non-AF HTN patients, significant microbial alterations (p = 0.004), including increased microbial diversity (p < 0.05), shifted enterotype dominated by Prevotella to Bacteroides, and abundant disease-linked genera Ruminococcus, Streptococcus, Veillonella, Dorea, and Enterococcus, were observed in HTN-AF patients. A species-based random forest prediction model was associated with the risk of AF occurrence in HTN patients. Furthermore, GM metabolic profiles dramatically differed between HTN and HTN-AF patients, especially the imbalance of saturated and unsaturated fatty acids. In HTN-AF patients, circulating palmitic acid and arachidonic acid levels were significantly elevated, while the levels of tetracosahexaenoic acid, oleic acid, linoleic acid, and stearic acid were decreased (p < 0.001, VIP > 1), mediating 85.99% of gut microbial indirect effects on AF (p < 0.001). Thus, our findings preliminarily indicated that exacerbated dysbiosis of GM and relevant metabolites was associated with high AF susceptibility and might be a potential target for AF prediction and prevention in HTN.

Objective This study was designed to explore the predictive value of plasma phenylalanine (Phe) and gut microbiota-derived metabolite phenylacetylglutamine (PAGln) in coronary in-stent restenosis (ISR). Methods Patients with coronary ISR, in-stent hyperplasia (ISH), and in-stent patency (ISP) were retrospectively enrolled in this study. Multivariable logistic regression analyses were used to identify independent risk factors of ISR. The predictive value of plasma Phe and PAGln levels was evaluated by receiver operating characteristic (ROC) curve analysis. The areas under the ROC curve (AUCs) were compared using the Z-test. The correlation between PAGln and clinical characteristics were examined using Spearman's correlation analysis. Results Seventy-two patients (mean age, 64.74 ± 9.47 years) were divided into three groups according to coronary stent patency: ISR (n = 28), ISH (n = 11), and ISP (n = 33) groups. The plasma levels of Phe and PAGln were significantly higher in the ISR group than in the ISP group. PAGln was positively associated with the erythrocyte sedimentation rate, homocysteine, SYNTAX score, triglyceride to high-density lipoprotein ratio, Phe, and microbiota-related intermediate metabolite phenylacetic acid (PA). In the ISR group, with the aggravation of restenosis, PAGln levels were also elevated. In multivariate regression analyses, Phe, PAGln and SYNTAX score were independent predictors of coronary ISR (all P < 0.05). In the ROC curve analyses, both Phe [AUC = 0.732; 95% confidence interval (CI), 0.606–0.858; P = 0.002] and PAGln (AUC = 0.861; 95% CI, 0.766–0.957; P < 0.001) had good discrimination performance in predicting coronary ISR, and the predictive power of PAGln was significantly better (P = 0.031). Conclusion Plasma Phe and PAGln are valuable indices for predicting coronary ISR, and gut microbes may be a promising intervention target to prevent ISR progression.

IntroductionDysbiotic gut microbiota (GM) plays a regulatory role during the pathogenesis of several cardiovascular diseases, including atherosclerosis. GM-derived metabolite phenylacetylglutamine (PAGln) enhances platelet responsiveness and thrombosis potential, thereby inducing major adverse cardiovascular events. However, the role of GM and microbial metabolite PAGln in the pathogenesis of in-stent stenosis remains unknown. Methods16S rRNA sequencing was performed on fecal samples in 103 coronary artery disease (CAD) patients, including 35 individuals with in-stent patency (control), 32 individuals with in-stent hyperplasia (ISH), and 36 subjects with in-stent stenosis (ISS), and the levels of plasma PAGln were evaluated by enzyme-linked immunosorbent assay. ResultsThe results revealed significantly enhanced microbial diversity and disrupted composition, such as enrichment of Roseburia, Blautia, and Ruminococcus, were observed in CAD patients with in-stent stenosis. The imbalance of microbial function related to PAGln synthesis and elevated plasma GM-derived metabolite PAGln levels was detected in CAD patients with in-stent stenosis. The GM-dependent diagnostic model could identify CAD patients with in-stent stenosis. ConclusionThe current study revealed the disordered signature, altered functions, and potential diagnostic ability of GM in CAD patients with in-stent hyperplasia and stenosis. Enhanced microbiota-derived PAGln synthesis-related functions and elevated plasma PAGln levels were associated with in-stent stenosis and hyperplasia in CAD patients. Thus, an intervention targeting gut microbes may be a promising strategy to prevent stent stenosis in patients with CAD.

Obstructive sleep apnea (OSA) is a clinical syndrome characterized by recurrent episodes of apnea or hypopnea of the upper airway, leading to increased negative intrathoracic pressure, sleep fragmentation, intermittent hypoxia during sleep, and increased risk for morbidity and mortality of affected patients. The gut microbiome plays a key role in OSA pathogenesis, and fecal metabolic profiling reflects the gut microbial functional readout and mediates host–microbiome interactions. Herein, we conducted a cohort study to explore fecal metabolic signatures distinguishing OSA (44 patients) from healthy controls (22 healthy controls) by untargeted gas chromatography–time-of-flight mass spectroscopy. Significant metabolic signatures were detected in stool samples of patients with OSA: 246 metabolites of 24 ontology classes were identified, and 48 metabolites of 6 ontology classes were shifted. An enrichment of arachidonic acid, docosahexaenoic acid, and 11Z-eicosenoic acid and reduction in stearic acid, 5-hydroxyindoleacetic acid, gluconic acid, and α-hyodeoxycholic acid were observed in stool samples from patients with OSA. Fecal variance resulted in alterations in potential metabolic activities and was thereby strongly associated with host phenotypes, such as pulse blood oxygen saturation and apnea-hypopnea index. The prediction model based on feces metabolomics was established to distinguish OSA from healthy controls with high accuracy. This study revealed the metabolomic signatures of patients with OSA in feces, and the findings provide evidence of an association between metabolome and OSA. Dong Y, Wang P, Lin J, et al. Characterization of fecal metabolome changes in patients with obstructive sleep apnea. J Clin Sleep Med. 2022;18(2):575–586.

The gut microbiota has a known complex association with atrial fibrillation (AF) progression, but the association of gut viruses with AF is undefined. Metagenomic data in a cohort of 50 AF patients and 50 matched controls were examined to profile the gut viral signals and determine their associations with intestinal bacteria and the AF phenotype. The gut viral alterations were examined, and the marked elevation of viral diversity, including increased Simpson, Shannon, and Pielou index, was revealed in AF patients. The specific alteration of the intestinal viral population, such as overgrowth of Streptococcus virus DT1 and Pseudomonas phage, as well as imbalanced gut viral function, dominated by integral component of the membrane, and metal ion binding were detected in AF patients. Moreover, regarding co-occurrence networks connecting viruses and bacterial organisms, increasingly disordered virus-bacteria linkages were seen in AF cases with severe AF progression. Notably, the associations of Synechococcus phage S-SM1 and Cronobacter phage CR5 with bacterial species were very tight in control individuals but markedly dampened in AF cases. Furthermore, the viral score built by the selected discriminative taxa between AF cases with or without recurrence after ablation was still significantly associated with recurrence (HR = 2.959, P = 0.0085), with a survival AUC of 0.878. We demonstrated for the first time that gut viral signatures are associated with AF, and suppressed viral-bacterial associations in AF suggest the gut virus might participate in AF progression, which has a potential value in predicting ablation outcomes.