Characteristics, Treatment, and In-Hospital Outcomes of Older Patients With STEMI Without Standard Modifiable Risk Factors.

Background: Strategies targeting standard modifiable cardiovascular risk factors (SMuRFs), including hypertension, diabetes, hypercholesterolemia, and smoking, have been well established to prevent coronary heart disease. However, few studies have evaluated the management and outcomes of older patients without SMuRFs after myocardial infarction. Objectives: The authors sought to evaluate the profile of patients with ST-segment elevation myocardial infarction (STEMI) aged ≥75 years without SMuRFs. Methods: This study is based on the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project. Patients aged ≥75 years with a first presentation of STEMI were enrolled in this study between November 2014 and December 2019. Modified Poisson regression was used to evaluate the association between SMuRF-less and in-hospital outcomes. Results: Among 10,775 patients with STEMI aged ≥75 years, 1,633 (15.16%) had no SMuRFs. Compared with those with SMuRF, SMuRF-less patients received less evidence-based treatment. In-hospital mortality was similar among patients with and without SMuRFs (5.44% vs 5.14%; P = 0.630). However, after adjustment for patient characteristics and treatment, being SMuRF-less was significantly associated with a reduced risk of mortality (RR: 0.80; 95% CI: 0.65-0.99; P = 0.043). SMuRF-less patients also had a significantly reduced risk of in-hospital death when only adjusting for in-hospital treatment (RR: 0.78; 95% CI: 0.63-0.98; P = 0.030), regardless of patient characteristics. Conclusions: Approximately 1 in 7 STEMI patients in China ≥75 years old had no SMuRFs. The similar mortality in patients with and without SMuRF can be partially explained by the inadequate in-hospital treatment of SMuRF-less patients. The quality of care for older patients without SMuRF should be improved. (CCC Project-Acture Coronary Syndrome; NCT02306616).

Association of obstructive sleep apnoea with long-term cardiovascular events in patients with acute coronary syndrome with or without hypertension: insight from the OSA-ACS project.

BACKGROUND: A close relationship exists between obstructive sleep apnoea (OSA) and hypertension. However, the impact of hypertension on the prognostic significance of OSA in patients with acute coronary syndrome (ACS) remains unclear. METHODS: This is a post hoc analysis of the OSA-ACS project, which consecutively included patients with ACS and receiving overnight sleep study from June 2015 to January 2020. OSA was defined as AHI ≥15 events/hour. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCE), including a composite of cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularisation or hospitalisation for unstable angina or heart failure. RESULTS: A total of 1927 patients with ACS were finally enrolled in this study. The mean patient age was 56.4±10.5 years. Among them, 1247 (64.7%) patients had hypertension, and 1014 (52.6%) patients had OSA. During 2.9 (1.5, 3.6) years of follow-up, OSA was associated with an increased risk of MACCE among patients with hypertension (HR=1.35, 95% CI 1.04 to 1.75, p=0.02), but not in patients without hypertension (HR=1.15, 95% CI 0.79 to 1.68, p=0.47). The interaction between OSA and hypertension for MACCE was not statistically significant (interaction p=0.29). For patients with pre-existing hypertension, OSA was associated with an increased risk of MACCE only among those with grade 3 hypertension (HR 1.54, 95% CI 1.12 to 2.13, p=0.008), but not those with grade 1 or 2 hypertension. CONCLUSIONS: OSA was associated with an increased risk of MACCE following ACS in patients with hypertension, especially in patients with pre-existing severe hypertension. These findings highlight the importance of identifying OSA in ACS patients with hypertension. TRIAL REGISTRATION NUMBER: NCT03362385.

Role of Bacterial Extracellular Vesicles in Manipulating Infection.

Mammalian-cell-derived extracellular vesicles, such as exosomes, have been a key focal point for investigating host-pathogen interactions and are major facilitators in modulating both bacterial and viral infection. However, in recent years, increasing attention has been given to extracellular vesicles produced by bacteria and the role they play in regulating infection and disease. Extracellular vesicles produced by pathogenic bacteria employ a myriad of strategies to assist in bacterial virulence or divert antibacterial responses away from the parental bacterium to promote infection by and survival of the parental bacterium. Commensal bacteria also produce extracellular vesicles. These vesicles can play a variety of roles during infection, depending on the bacterium, but have been primarily shown to aid the host by stimulating innate immune responses to control infection by both bacteria and viruses. This article will review the activities of bacterial extracellular vesicles known to modulate infection by bacterial and viral pathogens.

Cardiac magnetic resonance shows increased adverse ventricular remodeling in younger patients after ST-segment elevation myocardial infarction.

OBJECTIVES: Young patients account for about half of ST-segment elevation myocardial infarction (STEMI) patients and display a unique risk profile compared with old patients. Whether these differences are related to disparities in ventricular remodeling remains unknown. This study aimed to evaluate age-related differences in ventricular remodeling after primary percutaneous coronary intervention (PPCI) for STEMI. METHODS: In this observational study, consecutive STEMI patients between October 2019 and March 2021 who underwent serial cardiovascular magnetic resonance at index admission (3 to 7 days) and 3 months after PPCI were enrolled. Adverse remodeling was defined as ≥ 10% enlargement in left ventricular end-diastolic volume index (LVEDVi), while reverse remodeling was defined as a decrease in left ventricular end-systolic volume index (LVESVi) of more than 10%. RESULTS: A total of 123 patients were included and grouped into young (< 60 years, n = 71) and old (≥ 60 years, n = 52) patients. Despite generally similar baseline structural and infarct characteristics, LVESVi significantly decreased only in old patients during follow-up (p = 0.034). The incidence of adverse remodeling was higher (49.3% vs 30.8%, p = 0.039), while the incidence of reverse remodeling was lower (31.0% vs 53.8%, p = 0.011) in young compared with old patients. Younger age (< 60 years) was associated with a significantly higher risk of adverse remodeling (adjusted OR 3.51, 95% CI 1.41-8.74, p = 0.007) and lower incidence of reverse remodeling (adjusted OR 0.42, 95% CI 0.18-0.97, p = 0.046). CONCLUSIONS: In STEMI patients undergoing PPCI, young patients are at a higher risk of adverse remodeling and less probably develop reverse remodeling than old patients. Equal or more attention should be paid to young patients with STEMI compared with their older counterparts. KEY POINTS: • In STEMI patients undergoing PPCI, young patients displayed unfavorable remodeling compared with old patients. • Young patients are at a higher risk of adverse remodeling and less probably develop reverse remodeling than old patients. • Equal or more attention should be paid to young patients compared with their older counterparts.

Effect of Aggregate Size and Water/Cement on Compressive Strength and Physiological Performance of Planting Concrete.

Planting concrete, an eco-friendly concrete in which plants can grow directly, has been widely used in roof greening and the slopes of rivers. Porosity and compressive strength are important indicators for evaluating the properties of planting concrete. By preparing planting concrete with different aggregate gradations (10-30 mm, 20-40 mm) and water-cement ratios (0.25, 0.27, 0.29, 0.31, 0.33), the effect of aggregate gradation and water-cement ratio on the porosity and compressive strength of the planting concrete was analyzed, the intrinsic relationship between aggregate gradation and plane pore parameters was studied, the strength growth pattern and microscopic strengthening mechanism were studied, the relationship between porosity and compressive strength of the planting concrete were explored, and a tall fescue planting experiment was carried out to evaluate the plantation performance of the planting concrete. The results show that under the same conditions of water-cement ratio, the smaller the particle size of the aggregate, the smaller the porosity of the plane, and the denser the structure. The average diameter of the planting concrete shows an exponential relationship with the porosity of plane. The early growth of the compressive strength of the planting concrete is rapid; the compressive strength has a linear relationship at the ages of 7 days and 28 days. Compared to polynomial and logarithmic functions, the exponential function gives a better insight into the relationship between the porosity and compressive strength of the planting concrete. Tall fescue seeds germinate and grow well; height, cover, and leaf rootstock and element content of plants can be used as indicators to assess the performance of vegetated concrete planting.

Early ACEI/ARB use and in-hospital outcomes of acute myocardial infarction patients with systolic blood pressure <100 mmHg and undergoing percutaneous coronary intervention: Findings from the CCC-ACS project.

Background: Few studies have evaluated whether acute myocardial infarction (AMI) patients with relatively low blood pressure benefit from early ACEI/ARB use in the era of percutaneous coronary intervention (PCI). Objectives: This study evaluated the associations of ACEI/ARB use within 24 h of admission with in-hospital outcomes among AMI patients with SBP < 100 mmHg and undergoing PCI. Methods: This study was based on the Improving Care for Cardiovascular Disease in China-ACS project, a collaborative registry and quality improvement project of the American Heart Association and the Chinese Society of Cardiology. Between November 2014 and December 2019, a total of 94,623 patients with AMI were enrolled. Of them, 4,478 AMI patients with SBP < 100 mmHg and undergoing PCI but without clinically diagnosed cardiogenic shock at admission were included. Multivariable logistic regression and propensity score-matching analysis were used to evaluate the association between early ACEI/ARB use and in-hospital major adverse cardiac events (MACEs), a combination of all-cause death, cardiogenic shock, and cardiac arrest. Results: Of AMI patients, 24.41% (n = 1,093) were prescribed ACEIs/ARBs within 24 h of admission. Patients with early ACEI/ARB use had a significantly lower rate of MACEs than those without ACEI/ARB use (1.67% vs. 3.66%, p = 0.001). In the logistic regression analysis, early ACEI/ARB use was associated with a 45% lower risk of MACEs (odds ratio: 0.55, 95% CI: 0.33-0.93; p = 0.027). Further propensity score-matching analysis still showed that patients with early ACEI/ARB use had a lower rate of MACEs (1.96% vs. 3.93%, p = 0.009). Conclusion: This study found that among AMI patients with an admission SBP < 100 mmHg undergoing PCI, early ACEI/ARB use was associated with better in-hospital outcomes. Additional studies of the early use of ACEIs/ARBs in AMI patients with relatively low blood pressure are warranted.

Bacterial extracellular vesicles control murine norovirus infection through modulation of antiviral immune responses.

Human norovirus is the primary cause of non-bacterial gastroenteritis globally and is the second leading cause of diarrheal deaths in children in developing countries. However, effective therapeutics which prevent or clear norovirus infection are not yet available due to a lack of understanding regarding norovirus pathogenesis. Evidence shows that noroviruses can bind to the surface of commensal bacteria, and the presence of these bacteria alters both acute and persistent murine norovirus infection through the modulation of host immune responses. Interestingly, norovirus-bacterial interactions also affect the bacteria by inducing bacterial stress responses and increasing the production of bacterial extracellular vesicles. Given the established ability of these vesicles to easily cross the intestinal barriers, enter the lamina propria, and modulate host responses, we hypothesized that bacterial extracellular vesicles influence murine norovirus infection through modulation of the antiviral immune response. In this study, we show that murine norovirus can attach to purified bacterial vesicles, facilitating co-inoculation of target cells with both virus and vesicle. Furthermore, we have found that when murine noroviruses and vesicles are used to co-inoculate macrophages, viral infection is reduced compared to virus infection alone. Specifically, co-inoculation with bacterial vesicles results in higher production and release of pro-inflammatory cytokines in response to viral infection. Ultimately, given that murine norovirus infection increases bacterial vesicle production in vivo, these data indicate that bacterial vesicles may serve as a mechanism by which murine norovirus infection is ultimately controlled and limited to a short-term disease.

De-escalation of antiplatelet therapy after percutaneous coronary intervention among East Asians and non-East Asians: a meta-analysis of randomized controlled trials.

BACKGROUND: To study the impact of de-escalation antiplatelet therapy retaining P2Y12 inhibition on major bleeding and ischemic outcomes after percutaneous coronary intervention (PCI) among East Asians and non-East Asians was unclear. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials through September 2020. Eight trials were included, which studied de-escalation of DAPT (D-DAPT, switching to P2Y12 inhibitor monotherapy, or switching to clopidogrel or dose reduction of the P2Y12 inhibitor after 1 to 3 months) versus 12 months standard DAPT (S-DAPT). The primary outcomes data was conducted using random effects models. RESULTS: Among the 8 included trials consisting of 37,775 patients, 62.6% presented with acute coronary syndrome. The median follow-up duration ranged from 12 to 24 months. Compared with S-DAPT, D-DAPT was associated with a lower risk of major bleeding (RR = 0.67, 95% CI 0.48-0.93, p = 0.02); however, this was only observed among East-Asians (RR = 0.61, 95% CI 0.37-0.99, p = 0.048). Among non-East Asians, the rate of major bleeding was similar between the two groups (RR = 0.73, 95% CI 0.46-1.14, p = 0.17, p for interaction = 0.59). There were no significant differences in the major adverse cardiovascular events (MACE) between D-DAPT and S-DAPT treatment among both East Asians (RR = 0.84, 95% CI 0.66-1.08, p = 0.18) and non-East Asians (RR = 0.89, 95% CI 0.79-1.00, p = 0.059, p for interaction = 0.71). CONCLUSIONS: The De-escalation strategy that retains P2Y12 inhibition after a PCI was associated with reduced risk of bleeding events, which was only demonstrated in East Asians patients, and not in non-East Asian patients.

School-based Hygiene Intervention to Prevent HelicObacter Pylori infection among childrEn (SHIP HOPE): protocol for a cluster-randomised controlled trial.

INTRODUCTION: Helicobacter pylori infection rates are high in China and worldwide, and maintaining good hygiene is effective in preventing H. pylori infection. Childhood is a critical stage for developing good hygiene practices. Therefore, in this study, we aimed to explore whether a comprehensive hygiene intervention can prevent H. pylori infection in primary schools in China. METHODS AND ANALYSIS: The School-based Hygiene Intervention to Prevent HelicObacter Pylori infection among childrEn study is a cluster-randomised controlled trial, which will include approximately 2400 children in grades 2-4 from 60 classes in 10 primary schools of Linqu County, Shandong Province. Schools will be randomly assigned (1:1) via a computer-generated list, to receive either comprehensive hygiene intervention (intervention) or the usual health education lessons (control), with stratification by area (urban or rural). The interventions will include the following: (1) Children's education: lessons and cartoon books designed to provide basic knowledge about hygiene, H. pylori, hand hygiene, diet and oral hygiene will be provided to children; (2) Caregiver's education: children will be empowered to share hygiene-related knowledge with their caregivers as homework; caregivers will be also invited to the school for hygiene lessons; (3) School hygiene promotion: suggestions will be provided for improving the hygienic environment. Children in control schools will receive usual health education lessons according to the arrangements of each school. The primary outcome is the prevalence and incidence of H. pylori infection among children at 1-year follow-up. The secondary outcomes are H. pylori and hygiene knowledge, family eating customs and hygiene practices among children and their caregivers, as well as school absences owing to diarrhoea. Additionally, growth in children is set as an exploratory outcome. General linear mixed models will be used to analyse differences between the intervention and control schools. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Institution Review Board of Tsinghua University (No: 20220020). Written informed consent will be obtained from each child and one of their caregivers. The findings of this study will be actively disseminated through scientific publications and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200056191.

Trends in Bleeding Events Among Patients With Acute Coronary Syndrome in China, 2015 to 2019: Insights From the CCC-ACS Project.

Objective: Major bleeding is a common complication following treatment for an acute coronary syndrome (ACS) and is associated with increased mortality. We aimed to explore the temporal trend of bleeding events in relation to changes of therapeutic strategies among patients hospitalized for ACS in China. Methods: The CCC-ACS project (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) is a collaborative initiative of the American Heart Association and the Chinese Society of Cardiology. We analyzed 113,567 ACS patients from 241 hospitals in China from 2015 to 2019. Major bleeding was defined as intracranial bleeding, retroperitoneal bleeding, a decline in hemoglobin levels ≥3 g/dL, transfusion with overt bleeding, bleeding requiring surgical intervention, and fatal bleeding. Kruskal-Wallis test was used to examine the trend of major bleeding over time. Results: The rate of in-hospital major bleeding decreased from 6.3% in 2015 to 4.7% in 2019 (unadjusted OR = 0.74, 95% CI: 0.68-0.80, and P < 0.001). The relative changes were consistent across almost all subgroups including patients with NSTE-ACS and STEMI, although the trend was more pronounced in NSTE-ACS patients. The decrease in bleeding was accompanied by a decrease in use of GP IIb/IIIa inhibitors and parenteral anticoagulation therapy during hospitalization. The annual reduced risk of bleeding (OR = 0.91, 95% CI: 0.89-0.93) was attenuated after stepwise adjusting for baseline characteristics and antithrombotic treatments (OR = 0.95, 95% CI: 0.93-0.97), but did not change after adjusting for invasive treatment (OR = 0.95, 95% CI: 0.93-0.97). Conclusions: There was a temporal reduction in in-hospital bleeding among Chinese ACS patients during the last 5 years, which was associated with more evidence-based use of antithrombotic therapies. Clinical Trial Registration: https://www.clinicaltrials.gov, identifier: NCT02306616.

Neutrophil Counts Help Predict Free Wall Rupture Following St-elevation Myocardial Infarction.

PURPOSE: Free wall rupture (FWR) is a lethal complication after acute myocardial infarction; however, the un-derlying mechanisms of FWR are unclear. This study analyzes the relationship between neutrophil counts and FWR following ST-elevation myocardial infarction (STEMI). METHODS: The case group was STEMI patients with FWR and the control group was STEMI patients without FWR (case-control ratio was 1:4). The demographic data, clinical manifestation and laboratory test results were retrospectively collected and analyzed. RESULTS: Of a total of 6,712 consecutive STEMI patients, 78 patients (1.2%) had FWR. Compared with STEMI patients, patients with FWR were older and more likely to be female with an anterior infarct. White blood cell (WBC) counts were significantly higher in the FWR group. Moreover, we found that the elevated neutrophil counts mainly accounted for the elevated WBC counts. There was also a correlation between the age and neu-trophil counts (P=0.0109); as patient age increased, neutrophil counts decreased (P=0.0387). We also found no correlation between neutrophil counts and the time between myocardial infarction attack and FWR; however, when dividing these patients into FWR ≤48 h after admission to hospital for STEMI and FWR >48 h, there was a significant difference in neutrophil counts (P=0.0196). Furthermore, the results of logistic regression analy-sis showed that increased neutrophil was an independent risk factor for FWR (odds ratio: 2.404, confidence interval: 1.055-5.477). CONCLUSION: Elevated neutrophil counts were found to be the main cause of differences in WBC counts be-tween FWR and STEMI. Elevated neutrophil was an independent risk factor for FWR. This study provided clues for further research and development of therapeutics for the prevention of FWR.

Role of Pulmonary Embolism Response Team in patients with intermediate- and high-risk pulmonary embolism: a concise review and preliminary experience from China.

Intermediate- and high-risk pulmonary embolism (PE) is a life-threatening medical emergency with high morbidity and mortality. Many of the treatment options for PE involve clinicians from multiple disciplines. Pulmonary Embolism Response Teams (PERTs) have been developed to coordinate the multidisciplinary team of clinicians to streamline the decision making process and develop individualised treatment plans in a timely fashion. The first PERT was established in 2012 and subsequently multiple centres worldwide have introduced this model for the management of intermediate- and high-risk PE. In this review, we evaluate the organisational structure and algorithms of different PERT services and compare data from pre- and post-PERT services to determine the impact of PERT on outcomes. We consider the cost and time implications of this multidisciplinary 24-hour service and suggest areas for further research and review.

A nitrogenase-like enzyme system catalyzes methionine, ethylene, and methane biogenesis.

Bacterial production of gaseous hydrocarbons such as ethylene and methane affects soil environments and atmospheric climate. We demonstrate that biogenic methane and ethylene from terrestrial and freshwater bacteria are directly produced by a previously unknown methionine biosynthesis pathway. This pathway, present in numerous species, uses a nitrogenase-like reductase that is distinct from known nitrogenases and nitrogenase-like reductases and specifically functions in C-S bond breakage to reduce ubiquitous and appreciable volatile organic sulfur compounds such as dimethyl sulfide and (2-methylthio)ethanol. Liberated methanethiol serves as the immediate precursor to methionine, while ethylene or methane is released into the environment. Anaerobic ethylene production by this pathway apparently explains the long-standing observation of ethylene accumulation in oxygen-depleted soils. Methane production reveals an additional bacterial pathway distinct from archaeal methanogenesis.

Optimal timing of staged percutaneous coronary intervention in ST-segment elevation myocardial infarction patients with multivessel disease.

BACKGROUND: Studies have shown that staged percutaneous coronary intervention (PCI) for non-culprit lesions is beneficial for prognosis of ST-segment elevation myocardial infarction (STEMI) patients with multivessel disease. However, the optimal timing of staged revascularization is still controversial. This study aimed to find the optimal timing of staged revascularization. METHODS: A total of 428 STEMI patients with multivessel disease who underwent primary PCI and staged PCI were included. According to the time interval between primary and staged PCI, patients were divided into three groups (≤ 1 week, 1-2 weeks, and 2-12 weeks after primary PCI). The primary endpoint was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal re-infarction, repeat revascularization, and stroke. Cox regression model was used to assess the association between staged PCI timing and risk of MACE. RESULTS: During the follow-up, 119 participants had MACEs. There was statistical difference in MACE incidence among the three groups (≤ 1 week: 23.0%; 1-2 weeks: 33.0%; 2-12 weeks: 40.0%; P = 0.001). In the multivariable adjustment model, the timing interval of staged PCI ≤ 1 week and 1-2 weeks were both significantly associated with a lower risk of MACE [hazard ratio (HR): 0.40, 95% confidence intervals (CI): 0.24-0.65; HR: 0.54, 95% CI: 0.31-0.93, respectively], mainly attributed to a lower risk of repeat revascularization (HR: 0.41, 95% CI: 0.24-0.70; HR: 0.36, 95% CI: 0.18-0.7), compared with a strategy of 2-12 weeks later of primary PCI. CONCLUSIONS: The optimal timing of staged PCI for non-culprit vessels should be within two weeks after primary PCI for STEMI patients.

In-Hospital Outcomes of Dual Loading Antiplatelet Therapy in Patients 75 Years and Older With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Findings From the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) Project.

BACKGROUND: Elderly patients with acute coronary syndrome (ACS) are at high risk for ischemic and bleeding events. This study aimed to evaluate the clinical effectiveness and safety of dual loading antiplatelet therapy for patients 75 years and older undergoing percutaneous coronary intervention for ACS. METHODS AND RESULTS: The Improving Care for Cardiovascular Disease in China-ACS project was a collaborative study of the American Heart Association and Chinese Society of Cardiology. A total of 5887 patients 75 years and older with ACS who had percutaneous coronary intervention and received dual antiplatelet therapy with aspirin and P2Y12 inhibitors (clopidogrel or ticagrelor) between November 2014 and June 2017 were enrolled. The primary effectiveness and safety outcomes were in-hospital major adverse cardiovascular events and major bleeding. Hazard ratios (HRs) of in-hospital outcomes with different loading statuses of antiplatelet therapy were estimated using Cox proportional hazard models with multivariate adjustment. A propensity score-matched analysis was also conducted. Compared with patients receiving a dual nonloading dose, patients taking a dual loading dose had increased risks of both major adverse cardiovascular events (HR, 1.66, 95% confidence interval, 1.13-2.44; [P=0.010]) and major bleeding (HR, 2.34, 95% confidence interval, 1.75-3.13; [P<0.001]). Among 3284 propensity score-matched patients, a dual loading dose was associated with a 1.36-fold risk of major adverse cardiovascular events (HR, 1.36; 95% confidence interval, 0.88-2.11 [P=0.168]) and a 2.08-fold risk of major bleeding (HR, 2.08; 95% confidence interval, 1.47-2.93 [P<0.001]). CONCLUSIONS: A dual loading dose of antiplatelet therapy was associated with increased major bleeding risk but not with decreased major adverse cardiovascular events risk among patients 75 years and older undergoing percutaneous coronary intervention for ACS in China. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02306616.

Predictive Validity of CRUSADE, ACTION and ACUITY-HORIZONS Bleeding Risk Scores in Chinese Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The CRUSADE, ACTION and ACUITY-HORIZONS bleeding scores have been derived using Caucasian patients, and little is known about which has the better predictive ability in Chinese patients, especially for patients with STEMI.Methods and Results:We retrospectively analyzed 2,208 consecutive STEMI patients undergoing primary PCI (PPCI). Major bleeding events were defined according to Bleeding Academic Research Consortium criteria (type 3 or 5). Predictive ability of the 3 scores was assessed using logistic regression and AUC. Unadjusted HR for 1-year death were determined on Cox proportional hazard modeling. The major bleeding rate was 2.4%. The AUC of the CRUSADE, ACTION and ACUTIY-HORIZONS models was 0.88 (95% CI: 0.84-0.92), 0.90 (95% CI: 0.87-0.94), and 0.78 (95% CI: 0.87-0.94). The calibration of the ACUTIY-HORIZONS model was not acceptable overall, or in the subgroup of access site (P<0.05). In the high-risk category, 1-year mortality was approximately 4-7-fold greater than in the low-risk category (CRUSADE: HR, 7.27; 95% CI: 3.30-16.02, P<0.001; ACTION: HR, 7.13; 95% CI: 2.19-15.41, P<0.001; ACUITY-HORIZONS: HR, 4.06; 95% CI: 1.62-10.16; P=0.003). CONCLUSIONS: The CRUSADE and ACTION scores have greater predictive ability for in-hospital major bleeding than the ACUITY-HORIZONS risk score in Chinese STEMI patients undergoing PPCI. Mortality would increase with the transition from low- to high-risk category in 1 year.

Effect of Potent P2Y12 Inhibitors on Ventricular Arrhythmias and Cardiac Dysfunction in Coronary Artery Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous studies have shown that P2Y12 receptor inhibitors might prevent ventricular arrhythmias and cardiac dysfunction in patients with coronary artery disease. However, few studies have focused on comparison of the efficacy of novel oral potent P2Y12 receptor inhibitors with clopidogrel on these outcomes. METHODS AND RESULTS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that were published in electronic databases of MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, and ClinicalTrials.gov before June 20, 2018. We compared the effect of prasugrel and ticagrelor with clopidogrel on outcomes of ventricular tachycardia (VT), ventricular fibrillation (VF), heart failure (HF), and cardiogenic shock (CS). Data were combined using both the fixed-effects models and the random-effects models, and the heterogeneity was assessed with the I 2 statistic. Nine RCTs (6 with prasugrel and 3 with ticagrelor) with 45,227 patients were included. Patients receiving prasugrel were associated with a lower risk of combined VT and VF (rate ratio [RR]: 0.72, 95% confidence interval [CI]: 95% CI: 0.52-0.99, p=0.043), as well as combined HF and CS (RR: 0.81, 95% CI: 0.70-0.94, p=0.005), compared with clopidogrel. Patients receiving ticagrelor were also associated with a reduced risk of VT and VF (RR: 0.85, 95% CI: 0.72-1.02, p=0.077), although without statistical significance, but not of HF and CS (RR: 0.96, 95% CI: 0.81-1.13, p=0.620). CONCLUSIONS: This meta-analysis of RCTs shows that, compared with clopidogrel, novel oral P2Y12 inhibitors, especially prasugrel, might have better effect on improving ventricular rhythm and cardiac function.

Comparison of the performance of the CRUSADE, ACUITY-HORIZONS, and ACTION bleeding scores in ACS patients undergoing PCI: insights from a cohort of 4939 patients in China.

BACKGROUND: The CRUSADE, ACTION and ACUITY-HORIZONS scores are commonly used for predicting in-hospital major bleeding events in patients with acute coronary syndrome (ACS), but the homogeneous nature of these models' population limits simple extrapolation to other local population. We aimed to compare the performance of the three risk models in Chinese patients. METHODS: We evaluated the performance of the three predicting scores for predicting in-hospital major bleeding events defined by thrombolysis in myocardial infarction (TIMI) serious (major and minor) episodes, in a cohort of Chinese ACS patients with either non-ST-elevation ACS (NSTE-ACS) or ST-elevation myocardial infarction (STEMI). Calibration and discrimination of the three risk models were evaluated by the Hosmer-Lemeshow test and C-statistic, respectively. We compared the predictive accuracy of the risk scores by the Delong non-parametric test. RESULTS: TIMI serious bleeding rate was 1.1% overall (1.9% and 0.86% for STEMI and NSTE-ACS, respectively). The CRUSADE, ACTION and ACUTIY-HORIZONS scores showed an adequate discriminatory capacity for major bleeding: in overall patients, the C-statistic was 0.80, 0.77, and 0.70, respectively; in NSTE-ACS patients, the C-statistic was 0.73, 0.72, and 0.64, respectively; in STEMI patients, the C-statistic was 0.91, 0.92, and 0.75, respectively. The C-statistic for the ACUITY-HORIZONS model was significantly lower than those of the CRUSADE and ACTION scores for the prediction of TIMI serious bleeding in overall patients (compared with CRUSADE, z = 3.83, P = 0.02; compared with ACTION, z = 3.51, P = 0.03); in NSTE-ACS patients (compared with CRUSADE, z = 2.37, P = 0.01; compared with ACTION, z = 2.11, P = 0.04), and in STEMI patients (compared with CRUSADE, z = 2.6.77, P = 0.02; compared with ACTION, z = 7.91, P = 0.002). No differences were observed when the CRUSADE and ACTION models were compared to each other, regardless of overall patients (z = 0.68, P = 0.31) and both of ACS types (NSTE-ACS, z = 0.52, P = 0.60), and STEMI patients (z = 0.36, P = 0.74). However, the three risk scores all overestimated the absolute major bleeding risk in each risk stratification in our study. For example, the predicted rate of CRUSADE score at high risk stratification was 11.9% vs. an actual rate of 5.3%. CONCLUSIONS: The CRUSADE and ACTION scores had a greater calibration and discrimination for in-hospital major bleeding compared with the ACUITY-HORIZONS score in Chinese patients with ACS undergoing PCI. However, they all overestimated the bleeding risk rate for Chinese populations. Calibration of these risk scores would be useful for the generalization in Chinese populations.

The ß3 Adrenergic Receptor Agonist BRL37344 Exacerbates Atrial Structural Remodeling Through iNOS Uncoupling in Canine Models of Atrial Fibrillation.

BACKGROUND/AIMS: The role of the ß3-adrenergic receptor (ß3-AR) agonist BRL37344 in atrial fibrillation (AF) structural remodeling and the underlying mechanisms as a therapeutic target were investigated. METHODS: Four groups of dogs were evaluated: sham, pacing, ß3-AR agonist BRL37344 (ß3-AGO), and ß3-AR antagonist L748337 (ß3-ANT) groups. Dogs in the pacing, ß3-AGO and ß3-ANT groups were subjected to rapid atrial pacing for four weeks. Atrial structure and function, AF inducibility and duration, atrial myocyte apoptosis and interstitial fibrosis were assessed. Atrial superoxide anions were evaluated by fluorescence microscopy and colorimetric assays. Cardiac nitrate+nitrite levels were used to assess nitric oxide (NO) production. Protein and mRNA expression of ß3-AR, neuronal NO synthase (nNOS), inducible NO synthase (iNOS), endothelial NO synthase (eNOS) and guanosine triphosphate cyclohydrolase-1 (GCH-1) as well as tetrahydrobiopterin (BH4) levels were measured. RESULTS: ß3-AR was up-regulated in AF. Stimulation of ß3-AR significantly increased atrial myocyte apoptosis, fibrosis and atrial dilatation, resulting in increased AF induction and prolonged duration. These effects were attenuated by ß3-ANT. Moreover, ß3-AGO reduced BH4 and NO production and increased superoxide production, which was inhibited by the specific iNOS inhibitor, 1400w ß3-AGO also increased iNOS but decreased eNOS and had no effect on nNOS expression in AF. CONCLUSIONS: ß3-AR stimulation resulted in atrial structural remodeling by increasing iNOS uncoupling and related oxidative stress. ß3-AR up-regulation and iNOS uncoupling might be underlying AF therapeutic targets.

Fenofibrate inhibits atrial metabolic remodelling in atrial fibrillation through PPAR-α/sirtuin 1/PGC-1α pathway.

BACKGROUND AND PURPOSE: Atrial metabolic remodelling is critical for the process of atrial fibrillation (AF). The PPAR-α/sirtuin 1 /PPAR co-activator α (PGC-1α) pathway plays an important role in maintaining energy metabolism. However, the effect of the PPAR-α agonist fenofibrate on AF is unclear. Therefore, the aim of this study was to determine the effect of fenofibrate on atrial metabolic remodelling in AF and explore its possible mechanisms of action. EXPERIMENTAL APPROACH: The expression of metabolic proteins was examined in the left atria of AF patients. Thirty-two rabbits were divided into sham, AF (pacing with 600 beats·min(-1) for 1 week), fenofibrate treated (pretreated with fenofibrate before pacing) and fenofibrate alone treated (for 2 weeks) groups. HL-1 cells were subjected to rapid pacing in the presence or absence of fenofibrate, the PPAR-α antagonist GW6471 or sirtuin 1-specific inhibitor EX527. Metabolic factors, circulating biochemical metabolites, atrial electrophysiology, adenine nucleotide levels and accumulation of glycogen and lipid droplets were assessed. KEY RESULTS: The PPAR-α/sirtuin 1/PGC-1α pathway was significantly inhibited in AF patients and in the rabbit/HL-1 cell models, resulting in a reduction of key downstream metabolic factors; this effect was significantly restored by fenofibrate. Fenofibrate prevented the alterations in circulating biochemical metabolites, reduced the level of adenine nucleotides and accumulation of glycogen and lipid droplets, reversed the shortened atrial effective refractory period and increased risk of AF. CONCLUSION AND IMPLICATIONS: Fenofibrate inhibited atrial metabolic remodelling in AF by regulating the PPAR-α/sirtuin 1/PGC-1α pathway. The present study may provide a novel therapeutic strategy for AF.