Bone fracture is associated with incident myocardial infarction in long-term follow-up.

BACKGROUND: The association between bone fracture and cardiovascular diseases is examined in this study. While basic research has established a connection between fractures and heart attacks through the linkage between bones and arteries, population studies have not provided clear evidence. The aim of the present study is to investigate the association between bone fracture and the occurrence of myocardial infarction in a natural population during long-term follow-up. METHODS: A total of 13,196 adult participants with bone fracture history at baseline from the China Health and Nutrition Survey (CHNS) prospective cohort were included in this study. Baseline investigation was performed in 1997-2009 and the outcome was followed up till 2015. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. RESULTS: From 1997 to 2015, a total of 329 incident myocardial infarction cases were identified. In univariate and multivariate Cox regression analysis, a history of bone fracture was associated with an increased risk of myocardial infarction incidence in the total population (for the crude model: HR = 2.56, 95% CI 1.83-3.53, P < 0.001; for the multivariate model: HR = 1.43, 95% CI 1.02-1.99, P = 0.036). In the stratified analysis, bone fracture was not associated with an increased risk of incident myocardial infarction in subjects with age < 50 years (HR = 0.71, 95% CI 0.34-1.47, P = 0.356), but significantly associated with an increased risk of incident myocardial infarction in subjects with age ≥ 50 years (HR = 1.80, 95% CI 1.23-2.63, P = 0.003). CONCLUSIONS: It is suggested by the present study that bone fracture may be associated with an increased risk of incident myocardial infarction in the elderly population during long-term follow-up.

High blood pressure is associated with increased risk of future fracture, but not vice versa.

The association between high blood pressure and fracture showed obvious discrepancies and were mostly between hypertension with future fracture, but rarely between fracture and incident hypertension. The present study aims to investigate the associations of hypertension with future fracture, and fracture with incident hypertension. We included adult participants from the China Health and Nutrition Survey (CHNS) prospective cohort in 1997-2015 (N = 10,227), 2000-2015 (N = 10,547), 2004-2015 (N = 10,909), and 2006-2015 (N = 11,121) (baseline in 1997, 2000, 2004, 2006 respectively and outcome in 2015). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. In the analysis of the association between hypertension and future fracture, the adjusted HRs (95% CIs) were 1.34 (0.95-1.90) in 1997-2015, 1.40 (1.04-1.88) in 2000-2015, 1.32 (0.98-1.78) in 2004-2015, and 1.38 (1.01-1.88) in 2006-2015. In the analysis of the association between fracture and incident hypertension, the adjusted HRs (95% CIs) were 1.28 (0.96-1.72) in 1997-2015, 1.18 (0.94-1.49) in 2000-2015, 1.12 (0.89-1.40) in 2004-2015, and 1.09 (0.85-1.38) in 2006-2015. The present study showed that hypertension history was associated with increased risk of future fracture, but not vice versa.

Transcription factor Dmrt1 triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility.

Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that Dmrt1 plays an important role in regulating testicular immune homeostasis. Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that Dmrt1 positively regulated the expression of Spry1, an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified Dmrt1- Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.

Efficacy of Chinese Herbal Medicines on Pregnancy Outcomes in Patients with Endometriosis in Long-Term Management: A Multicenter Retrospective Cohort Study.

OBJECTIVE: To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. METHODS: This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. RESULTS: The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CONCLUSION: CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.

A Novel Reperfusion Strategy for Primary Percutaneous Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction: A Prospective Case Series.

BACKGROUND: Ischemia reperfusion injury (IRI) remains a major problem in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). We have developed a novel reperfusion strategy for PCI and named it "volume-controlled reperfusion (VCR)". The aim of the current study was to assess the safety and feasibility of VCR in patients with STEMI. METHODS: Consecutive patients admitted to Beijing Chaoyang Hospital with STEMI were prospectively enrolled. The feasibility endpoint was procedural success. The safety endpoints included death from all causes, major vascular complications, and major adverse cardiac event (MACE), i.e., a composite of cardiac death, myocardial reinfarction, target vessel revascularization (TVR), and heart failure. RESULTS: A total of 30 patients were finally included. Procedural success was achieved in 28 (93.3%) patients. No patients died during the study and no major vascular complications or MACE occurred during hospitalization. With the exception of one patient (3.3%) who underwent TVR three months after discharge, no patient encountered death (0.0%), major vascular complications (0.0%), or and other MACEs (0.0%) during the median follow-up of 16 months. CONCLUSION: The findings of the pilot study suggest that VCR has favorable feasibility and safety in patients with STEMI. Further larger randomized trials are required to evaluate the effectiveness of VCR in STEMI patients.

OCT6 inhibits differentiation of porcine-induced pluripotent stem cells through MAPK and PI3K signaling regulation.

As a transcription factor of the Pit-Oct-Unc (POU) domain family, octamer-binding transcription factor 6 ( OCT6) participates in various aspects of stem cell development and differentiation. At present, however, its role in porcine-induced pluripotent stem cells (piPSCs) remains unclear. Here, we explored the function of OCT6 in piPSCs. We found that piPSCs overexpressing OCT6 maintained colony morphology and pluripotency under differentiation conditions, with a similar gene expression pattern to that of non-differentiated piPSCs. Functional analysis revealed that OCT6 attenuated the adverse effects of extracellular signal-regulated kinase (ERK) signaling pathway inhibition on piPSC pluripotency by activating phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling activity. Our research sheds new light on the mechanism by which OCT6 promotes PSC maintenance.

Ablation index-guided ablation with milder targets for atrial fibrillation: Comparison between high power and low power ablation.

Background: High power-ablation index (HP-AI)-guided ablation for atrial fibrillation (AF) targeting high AIs has been implemented in European countries. However, milder AI targets are widely used in Asia. The safety and efficacy of HP-AI-guided ablation compared with those of low-power AI-guided ablation in a milder AI-targeting setting are unknown. The goal of this study was to explore the efficacy and safety of HP-AI-guided ablation in a milder AI-targeting setting. Methods: Patients who underwent pulmonary vein isolation (PVI) for AI-guided atrial fibrillation ablation in our center were enrolled and divided into 2 groups according to the ablation power used. In the HP-AI group, the ablation power was over 45 W, while the low power-AI group was ablated with <35 W power. The targeted AIs were 450-500 in the anterior wall and 350-400 in the posterior wall. The efficacy outcome was expressed as the single-procedure atrial arrhythmia-free survival between 91 days and 1 year. Safety outcomes included severe adverse events (SAEs), including symptomatic pulmonary vein (PV) stenosis, atrioesophagal fistula, cardiac tamponade, stroke, thromboembolism events, myocardial infarction, and major bleeding. Results: A total of 134 patients were enrolled, of whom 74 underwent PVI using HP-AI, while 60 received low power-AI ablation. After a mean follow-up time of 7.4 months, 22 (16.4%) patients showed arrhythmia recurrence: 5 (6.8%) patients in the HP-AI group and 17 (28.3%) patients in the low power-AI group. The HP-AI group showed a significantly higher arrhythmia-free survival than the low power-AI group (p = 0.011). Two patients in the low power-AI group and 1 patient in the HP-AI group developed an SAE (p = NS). Compared with the low power-AI group, the HP-AI group demonstrated a higher PV first-pass isolation rate, shorter ablation time, and fewer patients with anatomical leakages and sites of unreached AI. Conclusion: In a milder AI setting, HP-AI ablation might result in significantly higher arrhythmia-free survival than low power-AI ablation and a similar safety profile.

Holistic review and meta-analysis of independent impact of the residual SYNTAX score on prognosis in patients with acute coronary syndrome.

Objectives. The appropriate extent of revascularization following primary intervention is unknown. We conducted a systematic review and meta-analysis of residual Syntax score (rSS) to predict the outcomes and provide guide to optimal management of revascularization following primary intervention. Designs. Previously published studies from 2007 to 2020 assessing the prognostic impact of rSS after ACS were included for this meta-analysis. The primary endpoint was defined as the major adverse clinical events (MACE) in multivariable analysis. The risk ratios (RRs) with 95% confidence intervals (CI) were calculated using the RevMan 5.4 software. Results. A total of 8,157 participants complicated with ACS from 12 clinical studies were included in this analysis. Based on the wide range of rSS studies available, we classified it into two major groups: rSS < 8 and rSS ≥ 8. In multivariate analysis, the rSS was an independent risk marker for MACE [RR = 1.04 (95%CI; 1.00-1.08)], all-cause mortality [RR = 1.05 (1.03-1.07)] and cardiovascular death [RR = 1.05 (1.03-1.07)]. Patients with incomplete revascularization (ICR) showed higher prevalence of MACE along with all-cause mortality, cardiovascular morality, and recurrent myocardial infarction without significant heterogeneity [RR = 1.60 (1.03-1.07), 2.30 (1.57-3.38), 3.57 (2.09-6.10) and 1.70 (1.38-2.09), respectively]. The patients with rSS ≥ 8 presented higher frequency of all-cause mortality [RR = 2.99 (2.18-4.09)], cardiovascular death [RR = 3.32 (2.22-4.95)], and recurrent myocardial infarction [RR = 1.64 (1.34-2.02)]. Conclusion. The meta-analysis indicated that an rSS value of 8 could be a reasonable cut-off for incomplete revascularization after ACS and is an efficient tool to guide revascularization. In future, detailed research should focus on investigation of the optimal value of the rSS score.

Toward the Controlled Synthesis of Highly Dispersed Metal Clusters Enabled by Downsizing Crystalline Porous Organic Cage Supports.

The controlled synthesis of subnanometer-sized metal clusters (MCs) presents a fascinating prospect for the research of size-dependent properties. In this study, a facile approach by employing porous racemic organic cage crystals as supports for immobilizing a broad range of noble MCs (e.g., Ru, Ir, Rh) is reported. Downsizing the support to the nanoscale leads to resultant MCs with precisely controlled sizes < 0.7 nm. Such enhanced stabilization ability is a result of enhanced metal-support interactions as well as the nanoconfinement of organic cages in controlling the growth of MCs. Moreover, the obtained MCs display excellent catalytic performance in a series of liquid-phase reactions owing to a decrease in the diffusion resistance from the substrate to MCs immobilized by the nano-sized cage support.

MiRNA-122-5p inhibitor abolishes angiotensin II-mediated loss of autophagy and promotion of apoptosis in rat cardiofibroblasts by modulation of the apelin-AMPK-mTOR signaling.

MicroRNAs (miRNAs) have emerged as essential regulators that could have pivotal roles in cardiac homeostasis and pathological remodeling of various cardiovascular diseases. We previously demonstrated that miRNA-122-5p overexpression exacerbated the process of vascular hypertrophy, fibrosis, and dysfunction in hypertensive rats and rat aortic adventitial fibroblasts. However, the exact roles and underlying mechanisms of miRNA-122-5p in myocardial fibroblasts remain largely unknown. In this work, neonatal rat cardiofibroblasts (CFs) were isolated and primarily cultured from the hearts of 2- to 3-d-old Sprague-Dawley rats. Stimulation of angiotensin II (Ang II) resulted in marked increases in cellular proliferation and migration and levels of collagen I, collagen III, CTGF, and TGF-ß1 in cultured CFs. Furthermore, Ang II led to promoted expression of P62, Bax, and phosphorylated mTOR as well as downregulation of LC3II, beclin-1, and AMPK-phosphorylated levels, thereby contributing to imbalance of autophagy and apoptosis, and cellular injury in CFs, which were significantly ameliorated by treatment with miRNA-122-5p inhibitor. These changes were associated with decreased levels of collagen I, collagen III, CTGF, and TGF-ß1. Furthermore, Ang II-induced loss of autophagy and promotion of apoptosis in CFs were prevented by the treatment with Pyr1-apelin-13 or AMPK agonist AICAR or mTOR inhibitor rapamycin, respectively. In contrast, administration of miRNA-122-5p mimics and autophagy inhibitor 3-methylademine reversed beneficial roles of Pyr1-apelin-13. Collectively, these data indicated that miRNA-122-5p is an essential regulator of autophagy and apoptosis in rat CFs via the apelin/AMPK/mTOR signaling pathway, which may be potentially used as a therapeutic target in myocardial fibrosis and related diseases.

Fração de Ejeção do Ventrículo Esquerdo Aumentada, Diminuída ou Estável ao Longo do Tempo em uma Série de 626 Pacientes com Insuficiência Cardíaca que Receberam Tratamento Médico / Increased, Decreased, or Stable Left Ventricle Ejection Fraction over Time in a Series of 626 Heart Failure Patients Receiving Medical Treatment

Resumo Fundamento: A fração de ejeção (FE) tem sido utilizada em análises fenotípicas e na tomada de decisões sobre o tratamento de insuficiência cardíaca (IC). Assim, a FE tornou-se parte fundamental da prática clínica diária. Objetivo: Este estudo tem como objetivo investigar características, preditores e desfechos associados a alterações da FE em pacientes com diferentes tipos de IC grave. Métodos: Foram incluídos neste estudo 626 pacientes com IC grave e classe III-IV da New York Heart Association (NYHA). Os pacientes foram classificados em três grupos de acordo com as alterações da FE, ou seja, FE aumentada (FE-A), definida como aumento da FE ≥10%, FE diminuída (FE-D), definida como diminuição da FE ≥10%, e FE estável (FE-E), definida como alteração da FE <10%. Valores p inferiores a 0,05 foram considerados significativos. Resultados: Dos 377 pacientes com IC grave, 23,3% apresentaram FE-A, 59,5% apresentaram FE-E e 17,2% apresentaram FE-D. Os resultados mostraram ainda 68,2% de insuficiência cardíaca com fração de ejeção reduzida (ICFEr) no grupo FE-A e 64,6% de insuficiência cardíaca com fração de ejeção preservada (ICFEp) no grupo FE-D. Os preditores de FE-A identificados foram faixa etária mais jovem, ausência de diabetes e fração de ejeção do ventrículo esquerdo (FEVE) menor. Já os preditores de FE-D encontrados foram ausência de fibrilação atrial, baixos níveis de ácido úrico e maior FEVE. Em um seguimento mediano de 40 meses, 44,8% dos pacientes foram vítimas de morte por todas as causas. Conclusão: Na IC grave, a ICFEr apresentou maior percentual no grupo FE-A e a ICFEp foi mais comum no grupo FE-D.

Abstract Background: Ejection fraction (EF) has been used in phenotype analyses and to make treatment decisions regarding heart failure (HF). Thus, EF has become a fundamental part of daily clinical practice. Objective: This study aims to investigate the characteristics, predictors, and outcomes associated with EF changes in patients with different types of severe HF. Methods: A total of 626 severe HF patients with New York Heart Association (NYHA) class III-IV were enrolled in this study. The patients were classified into three groups according to EF changes, namely, increased EF (EF-I), defined as an EF increase ≥10%, decreased EF (EF-D), defined as an EF decrease ≥10%, and stable EF (EF-S), defined as an EF change <10%. A p-value lower than 0.05 was considered significant. Results: Out of 377 severe HF patients, 23.3% presented EF-I, 59.5% presented EF-S, and 17.2% presented EF-D. The results further showed 68.2% of heart failure with reduced ejection fraction (HFrEF) in the EF-I group and 64.6% of heart failure with preserved ejection fraction (HFpEF) in the EF-D group. The predictors of EF-I included younger age, absence of diabetes, and lower left ventricular ejection fraction (LVEF). The predictors of EF-D were absence of atrial fibrillation, lower uric acid level, and higher LVEF. Within a median follow-up of 40 months, 44.8% of patients suffered from all-cause death. Conclusion: In severe HF, HFrEF presented the highest percentage in the EF-I group, and HFpEF was most common in the EF-D group.

Incidence and Outcome of Acute Myocardial Infarction in Patients With Aortic Dissection and Risk Factor Control.

Background and Aims: The contradiction of management modality between acute myocardial infarction(AMI) and aortic dissection(AD) may result in clinical catastrophe. Data on risk factors, incidence, and outcome of AD and AMI are limited, and there have been no studies on the long-term outcomes of AMI in patients with AD. So we aimed to investigate long-term outcomes after AMI in patients with AD, and propose a useful diagnostic paradigm. Methods: Consecutively enrolled patients with AD and AMI who were referred to our center from 2010 to 2017. Baseline patient characteristics, risk factors, all medical treatments, echocardiographic parameters, laboratory data, and treatment were recorded. All patients were followed up from the first hospitalization until a first heart event, death, or 17 March, 2018. Results: 0.13% in AMI and 7.49% in AD patients had a concomitant diagnosis of AD and AMI. The average patient age was 53.3 ± 12.1 years and 84.6% were male. The most prevalent vascular risk factors were hypertension (69.2%) and current smoker (64.1%). Of all the 39 patients, 66.7% were managed surgically. Overall in-hospital mortality was 10.3%. The 30-day and 5-year fatality rates were 23.1% and 35.9%, but were higher for female than for male (66.7 vs. 30.3%, log-rank P = 0.045) on 5-year mortality. The overall survival of females was inferior to the males (log-rank P = 0.045). Conclusions: Patients with AMI and AD exhibit high 5-year fatality rates. For these patients, surgical management tends to have lower mortality. Improved management of hypertension and smoking, may reduce future incidence rates.

Increased, Decreased, or Stable Left Ventricle Ejection Fraction over Time in a Series of 626 Heart Failure Patients Receiving Medical Treatment. / Fração de Ejeção do Ventrículo Esquerdo Aumentada, Diminuída ou Estável ao Longo do Tempo em uma Série de 626 Pacientes com Insuficiência Cardíaca que Receberam Tratamento Médico.

BACKGROUND: Ejection fraction (EF) has been used in phenotype analyses and to make treatment decisions regarding heart failure (HF). Thus, EF has become a fundamental part of daily clinical practice. OBJECTIVE: This study aims to investigate the characteristics, predictors, and outcomes associated with EF changes in patients with different types of severe HF. METHODS: A total of 626 severe HF patients with New York Heart Association (NYHA) class III-IV were enrolled in this study. The patients were classified into three groups according to EF changes, namely, increased EF (EF-I), defined as an EF increase ≥10%, decreased EF (EF-D), defined as an EF decrease ≥10%, and stable EF (EF-S), defined as an EF change <10%. A p-value lower than 0.05 was considered significant. RESULTS: Out of 377 severe HF patients, 23.3% presented EF-I, 59.5% presented EF-S, and 17.2% presented EF-D. The results further showed 68.2% of heart failure with reduced ejection fraction (HFrEF) in the EF-I group and 64.6% of heart failure with preserved ejection fraction (HFpEF) in the EF-D group. The predictors of EF-I included younger age, absence of diabetes, and lower left ventricular ejection fraction (LVEF). The predictors of EF-D were absence of atrial fibrillation, lower uric acid level, and higher LVEF. Within a median follow-up of 40 months, 44.8% of patients suffered from all-cause death. CONCLUSION: In severe HF, HFrEF presented the highest percentage in the EF-I group, and HFpEF was most common in the EF-D group.

FUNDAMENTO: A fração de ejeção (FE) tem sido utilizada em análises fenotípicas e na tomada de decisões sobre o tratamento de insuficiência cardíaca (IC). Assim, a FE tornou-se parte fundamental da prática clínica diária. OBJETIVO: Este estudo tem como objetivo investigar características, preditores e desfechos associados a alterações da FE em pacientes com diferentes tipos de IC grave. MÉTODOS: Foram incluídos neste estudo 626 pacientes com IC grave e classe III­IV da New York Heart Association (NYHA). Os pacientes foram classificados em três grupos de acordo com as alterações da FE, ou seja, FE aumentada (FE-A), definida como aumento da FE ≥10%, FE diminuída (FE-D), definida como diminuição da FE ≥10%, e FE estável (FE-E), definida como alteração da FE <10%. Valores p inferiores a 0,05 foram considerados significativos. RESULTADOS: Dos 377 pacientes com IC grave, 23,3% apresentaram FE-A, 59,5% apresentaram FE-E e 17,2% apresentaram FE-D. Os resultados mostraram ainda 68,2% de insuficiência cardíaca com fração de ejeção reduzida (ICFEr) no grupo FE-A e 64,6% de insuficiência cardíaca com fração de ejeção preservada (ICFEp) no grupo FE-D. Os preditores de FE-A identificados foram faixa etária mais jovem, ausência de diabetes e fração de ejeção do ventrículo esquerdo (FEVE) menor. Já os preditores de FE-D encontrados foram ausência de fibrilação atrial, baixos níveis de ácido úrico e maior FEVE. Em um seguimento mediano de 40 meses, 44,8% dos pacientes foram vítimas de morte por todas as causas. CONCLUSÃO: Na IC grave, a ICFEr apresentou maior percentual no grupo FE-A e a ICFEp foi mais comum no grupo FE-D.

Declined ELABELA plasma levels in hypertension patients with atrial fibrillation: a case control study.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia in patients with hypertension. ELABELA, which has cardioprotective effects, is decreased in the plasma of patients with hypertension and might be associated with AF in the hypertensive population. This study aims to measure the ELABELA plasma levels in hypertension patients with and without AF and to analyse the related factors. METHODS: A total of 162 hypertension patients with or without AF were recruited for our monocentric observational study. Subjects were excluded if they had a history of valvular heart disease, rheumatic heart disease, cardiomyopathy, thyroid diseases, or heart failure. The patients' histories were recorded, and laboratory examinations were conducted. Plasma ELABELA was detected by immunoassay. Echocardiographs were performed, and parameters were collected by two experienced doctors. Binary logistic regression analysis was used to identify the association between ELABELA plasma level and AF in patients with hypertension. RESULTS: Plasma ELABELA levels were lower in hypertension patients with AF than in those without AF (2.0 [1.5, 2.8] vs. 4.0 [3.4, 5.0] ng/ml, P < 0.001). ELABELA levels were correlated with age, heart rate, BNP levels and left atrial dimension. In addition to the left atrial dimension, ELABELA plasma levels were associated with AF in patients with hypertension (OR 0.081, 95% CI 0.029-0.224, P < 0.001). ELABELA levels were further decreased in the persistent AF subgroup compared with the paroxysmal AF subgroup (1.8 [1.4, 2.5] vs. 2.2 [1.8, 3.0] ng/ml, P = 0.012) and correlated with HR, BNP and ESR levels. CONCLUSIONS: ELALABELA levels were decreased in hypertension patients with AF and further lowered in the persistent AF subgroup. Decreased ELABELA plasma levels were associated with AF in hypertension patients and may be an underlying risk factor.

Elabela prevents angiotensin II-induced apoptosis and inflammation in rat aortic adventitial fibroblasts via the activation of FGF21-ACE2 signaling.

Apoptosis, inflammation, and fibrosis contribute to vascular remodeling and injury. Elabela (ELA) serves as a crucial regulator to maintain vascular function and has been implicated in the pathogenesis of hypertensive vascular remodeling. This study aims to explore regulatory roles and underlying mechanisms of ELA in rat aortic adventitial fibroblasts (AFs) in response to angiotensin II (ATII). In cultured AFs, exposure to ATII resulted in marked decreases in mRNA and protein levels of ELA, fibroblast growth factor 21 (FGF21), and angiotensin-converting enzyme 2 (ACE2) as well as increases in apoptosis, inflammation, oxidative stress, and cellular migration, which were partially blocked by the exogenous replenishment of ELA and recombinant FGF21, respectively. Moreover, treatment with ELA strikingly reversed ATII-mediated the loss of FGF21 and ACE2 levels in rat aortic AFs. FGF21 knockdown with small interfering RNA (siRNA) significantly counterbalanced protective effects of ELA on ATII-mediated the promotion of cell migration, apoptosis, inflammatory, and oxidative injury in rat aortic AFs. More importantly, pretreatment with recombinant FGF21 strikingly inhibited ATII-mediated the loss of ACE2 and the augmentation of cell apoptosis, oxidative stress, and inflammatory injury in rat aortic AFs, which were partially prevented by the knockdown of ACE2 with siRNA. In summary, ELA exerts its anti-apoptotic, anti-inflammatory, and anti-oxidant effects in rat aortic AFs via activation of the FGF21-ACE2 signaling. ELA may represent a potential candidate to predict vascular damage and targeting the FGF21-ACE2 signaling may be a promising therapeutic intervention for vascular adventitial remodeling and related disorders.

Pulmonary vein isolation guided by moderate ablation index targets combined with strict procedural endpoints for patients with paroxysmal atrial fibrillation.

INTRODUCTION: Ablation index (AI)-guided radiofrequency ablation has been increasingly used for the treatment of drug-resistant paroxysmal atrial fibrillation (AF)，but the optimal AI targets remain to be determined. We aimed to examine the efficacy and safety of catheter ablation guided by moderate AI values but more strict procedural endpoints in patients with paroxysmal AF. METHODS: We conducted a retrospective review of a consecutive series of patients who received their first AI-guided ablation for paroxysmal AF from 2017 to 2018. The standard procedural protocol recommends AI targets as follows: anterior: 400-450; posterior: 280-330; and roof/inferior wall: 380-430. After circumferential pulmonary vein isolation (PVI), we performed bipolar pacing along the ablation line, adenosine triphosphate (ATP)-provocation, and waited for 30 min to verify PVI. The primary clinical outcome was the rate of freedom from AF recurrence at 12 months. RESULTS: A total of 140 consecutive patients were included. The mean procedure and ablation times were 132.2 ± 30.2 min and 24.2 ± 7.9 min, respectively. The first-pass isolation and final isolation rates were documented in 49.3% and in 100% of the patients, respectively. At 12 months, single-procedure freedom from atrial tachyarrhythmias was observed in 92.1% of patients. No major procedure-related complications were encountered. CONCLUSIONS: Moderate AI-guided catheter ablation is highly effective for the treatment of drug-refractory paroxysmal AF in real-world settings. Over 90% of patients achieved single-procedure arrhythmia-free survival at 1 year. The outcome was obtained without major complications and the procedure involved relatively short procedure and ablation times.

Impact of Prior Digestive System Disease on In-Hospital Gastrointestinal Bleeding in Patients with Acute Myocardial Infarction.

OBJECTIVE: Patients presenting with acute myocardial infarction (AMI) with prior digestive system disease are more likely to suffer from gastrointestinal (GI) bleeding than those without these diseases. However, few articles reported how the different conditions of the digestive tract produced different risks of GI bleeding. METHODS: A single-center study on 7464 patients admitted for AMI from December 2010 to June 2019 in the Beijing Chaoyang Heart Center was retrospectively examined. Patients with major GI bleeding (n = 165) were compared with patients without (n = 7299). Univariate and multivariate logistic regression models were constructed to test the association between GI bleeding and prior diseases of the digestive tract, including gastroesophageal reflux disease, chronic gastritis, peptic ulcer, hepatic function damage, diseases of the colon and rectum, and gastroenterological tract tumors. RESULTS: Of the 7464 patients (mean age, 63.4; women, 25.6%; STEMI, 58.6%), 165 (2.2%) experienced major GI bleeding, and 1816 (24.3%) had a history of digestive system disease. The risk of GI bleeding was significantly associated with peptic ulcer (OR = 4.19, 95% CI: 1.86-9.45) and gastroenterological tumor (OR = 2.74, 95% CI: 1.07-7.04), indicated by multivariate logistic regression analysis. CONCLUSION: Preexisting peptic ulcers and gastroenterological tract tumors rather than other digestive system diseases were indicators of gastrointestinal bleeding in patients with AMI who undergo standard antithrombotic treatment during hospitalization.

Cardiovascular complications of SARS-CoV-2 infection (COVID-19): a systematic review and meta-analysis.

Coronavirus Disease 2019 (COVID-19) originated in Wuhan, China in December 2019 and rapidly spread worldwide. Herein, we conducted a systematic review and meta-analysis to find the association between COVID-19 and cardiovascular complications. We conducted a systematic literature search of the PubMed and Embase databases from 01 December 2019 to 30 November 2020. We then statistically analyzed the incidence of cardiovascular complications in COVID-19 patients. We included 3044 confirmed COVID-19 cases from 12 studies. The most common cardiovascular complications in COVID-19 patients were myocardial injury (21.2%, 95% CI 12.3-30.0%) and arrhythmia (15.3%, 95% CI 8.4-22.3%), followed by heart failure (14.4%, 95% CI 5.7-23.1%) and acute coronary syndrome (1.0%, 95% CI 0.5-1.5%). The pooled incidence of heart failure, arrhythmia and myocardial injury in non-survivors were 47.8% (95% CI 41.4-54.2%), 40.3% (95% CI 1.6-78.9%) and 61.7% (95% CI 46.8-76.6%), respectively. Also, the data separately showed significantly higher incidence of heart failure and cardiac injury in non-survivors (relative risks = 5.13, 95% CI 2.46-10.7, Z = 4.36, P = 0.017) and (relative risks = 6.91, 95% CI 3.19-14.95, Z = 4.91, P = 0.009). Myocardial injury and arrhythmia were the most common complications in COVID-19 patients. Myocardial injury and heart failure were more common in patients who died, regardless of a history of cardiovascular disease. The incidence of heart failure and myocardial injury were higher in non-survivors compared to the survivors. Accordingly, in addition to basic support, cardiac reactions of patients with confirmed COVID-19 with or without underlying cardiovascular diseases should be closely monitored.

In-hospital outcome of primary PCI for patients with acute myocardial infarction and prior coronary artery bypass grafting.

BACKGROUND: This study aims to analyze the in-hospital outcome of primary percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI) and prior coronary artery bypass grafting (CABG). METHODS: This was a retrospective study. From January 2011 to December 2018, the data of 78 consecutive patients (study group) with prior CABG, who received primary coronary angiography in the setting of ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI), were screened. The study group was compared with another well-matched 78 patients without a history of CABG (control group). The information of the coronary angiograms and clinical data of both groups were analyzed. Multivariate conditional logistic regression models were constructed to test the association between PCI success rate and the prior CABG at age ≥65 and <65 years, respectively. RESULTS: The results revealed that the primary PCI success rate in the study group was significantly lower than in the control group (67.9% vs. 92.3%, P<0.001) and in-hospital mortality was significantly higher than in control group (11.5% vs. 2.5%, P=0.03). The multivariate logistic regression analysis indicated that the primary PCI success rate was significantly associated with the history of prior CABG both in young patients [age <65 years; odds ratio (OR) =5.26, 95% confidence interval (CI): 1.69-16.47] and elderly (age ≥65 years; OR =13.76, 95% CI: 2.72-69.75). CONCLUSIONS: The patients who receive primary PCI with AMI and prior CABG have poor in-hospital outcomes, with low PCI success rates and high mortality.

Does taking an angiotensin inhibitor increase the risk for COVID-19? - a systematic review and meta-analysis.

Because SARS-COV2 entry into cells is dependent on angiotensin converting enzyme 2 (ACE2) and angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) increase ACE2 activity, the safety of ACEI/ARB usage during the coronavirus disease 2019 (COVID-19) pandemic is a controversial topic. To address that issue, we performed a meta-analysis following The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Searches of the Embase, MEDLINE, PubMed, and Cochrane Library databases identified 16 case-control studies examining the effect of ACEI/ARB on the incidence of COVID-19 and its severity. ACEI/ARB usage was associated with an increased risk of COVID-19 morbidity (odds ratio (OR) 1.20, 95% confidence interval (CI) 1.07-1.33, P=0.001) among the general population but not in a hypertensive population (OR 1.05, 95% CI 0.90-1.21, P=0.553). ACEI/ARB usage was not associated with an increased risk of COVID-19 morbidity (coefficient 1.00, 95% CI 1.00-1.00, P=0.660) when we adjusted for hypertension in the general population. ACEI/ARB usage was also not associated with an increased risk of severe illness (OR 0.90, 95%CI 0.55-1.47, P=0.664) or mortality (OR 1.43, 95%CI 0.97-2.10, P=0.070) in COVID-19 patients. Our meta-analysis revealed that ACEI/ARB usage was not associated with either the increased risk of SARS-COV2 infection or the adverse outcomes in COVID-19 patients.