Implementation of CYP2C19 genotyping and clinical outcomes following percutaneous coronary intervention in East Asian patients treated with oral P2Y12 inhibitors.

BACKGROUND: The CYP2C19 loss-of-function variants have significant impact on response to clopidogrel. The efficacy and safety of tailored antiplatelet therapy under the guidance of CYP2C19 genetic polymorphisms remains elusive for patients undergoing percutaneous coronary intervention (PCI). OBJECTIVES: The aims of the present study were to investigate the impact of clinical implementation of CYP2C19 genotyping on the selection of oral P2Y12 inhibitor therapy following PCI, and to estimate the risk of adverse outcomes for patients with different genotype status treated with alternative or traditional P2Y12 inhibitor. METHODS: Data from a single-center registry enrolling 41,090 consecutive PCI patients treated with dual antiplatelet therapy after PCI were analyzed. Risk of major adverse cardiovascular events (MACEs) and bleeding events within 12 months after PCI were compared across CYP2C19 genotype and antiplatelet therapy groups using Cox proportional hazards models. RESULTS: CYP2C19 genotyping was successfully achieved for 9081 patients, of whom baseline characteristics significantly differed from non-genotyped patients. A higher proportion of genotyped patients were prescribed ticagrelor compared with non-genotyped patients (27.0 % vs. 15.5 %, P < 0.001). CYP2C19 metabolic status was an independent predictor for use of ticagrelor (P < 0.001). Ticagrelor was significantly associated with a lower risk of MACEs in poor metabolizers (adjusted hazard ratio 0.62, 95 % confidence interval 0.42 to 0.92, P = 0.017), but not in intermediate metabolizers or normal metabolizers. The interaction was not statistically significant (P for interaction = 0.252). CONCLUSIONS: Genotype information on CYP2C19 metabolic status was associated with an increase in the use of potent antiplatelet therapy in PCI patients. Patients prescribed with clopidogrel has a higher risk of MACEs among poor metabolizers, which suggested the potential application of genotype-guided P2Y12 inhibitor selection for improving clinical outcomes.

Prevalence, Predictors, and Impact of Coronary Artery Ectasia in Patients With Atherosclerotic Heart Disease.

The clinical relevance of coronary artery ectasia (CAE) is poorly understood. We investigated the prevalence, potential predictors, and prognostic significance of CAE in patients with atherosclerotic coronary artery disease. Consecutive patients undergoing percutaneous coronary intervention (PCI) from January 2016 to December 2018 were included and followed up for 1 year. CAE was diagnosed as an abnormal dilation >1.5-fold the diameter of adjacent normal segments on angiography. A total of 590 patients with CAE were identified from 36 790 patients undergoing PCI (overall rate of CAE: 1.6%). In multivariate analysis, variables including body mass index >30 kg/m2 (risk ratio, RR: 2.413, P = .018), ever-smoking (RR: 1.669, P < .001), hypertension (RR: 1.221, P = .025), acute myocardial infarction at admission (RR: 1.343, P = .004), no diabetes (RR: .810, P = .023), previous myocardial infarction (RR: 1.545, P < .001), no left main disease (RR: .632, P = .008) and multiple-vessel disease (RR: 1.326, P = .001), increased C-reactive protein (RR: 1.006, P = .012) were predictors of CAE. The incidence of adverse cardiovascular outcomes did not differ significantly between patients with or without CAE (P = .203). CAE is not uncommon among patients undergoing PCI in this cohort study. The presence of CAE vs its absence had no significant impact on 1-year clinical outcomes after PCI.

Short sleep duration and the risk of nonalcoholic fatty liver disease/metabolic associated fatty liver disease: a systematic review and meta-analysis.

PURPOSE: It is unclear whether or not nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated fatty liver disease (MAFLD) is related to short sleep duration. A meta-analysis was conducted to determine if inadequate sleep time increased the risk of NAFLD/MAFLD. METHODS: A comprehensive systematic literature review was conducted in the Embase, PubMed, and Cochrane Library databases from inception to August 1, 2022. Studies examining the correlation between inadequate sleep time and the risk of NAFLD/MAFLD were included. We pooled the odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. RESULTS: This meta-analysis included fifteen studies involving a total of 261,554 participants. In the pooled analysis, short sleep duration was found to be strongly correlated with an increased risk of NAFLD/MAFLD (OR, 1.15; 95% CI, 1.04-1.28; P = 0.01), with a moderate degree of heterogeneity between studies (I2 = 71.92%, Q = 49.87, P < 0.01). The sensitivity analysis suggested that the primary outcome was robust, and there was no significant publication bias. CONCLUSION: This meta-analysis indicates that inadequate sleep duration is strongly correlated with an elevated risk of NAFLD/MAFLD. The findings suggest that obtaining an adequate amount of sleep may be useful for preventing NAFLD/MAFLD, which is especially important given the low rate of response to pharmacotherapy.

Remnant-Like Particle Cholesterol and the Risk of Major Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis.

Background: The remnant-like particle cholesterol (RLP-C) has been demonstrated to be associated with residual cardiovascular risk. The meta-analysis aimed to evaluate the impact of baseline RLP-C on the incidence of major cardiovascular adverse events (MACEs) in patients with coronary artery disease (CAD). Methods: A systematic literature search was performed in PubMed and Embase electronic databases from the inception of the databases through 1 October 2022. Studies evaluating the association between baseline RLP-C and the risk of MACEs in patients with CAD were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled by a random-effect method (RLP-C analyzed as a categorical variable) and a fixed-effects model (RLP-C analyzed as a continuous variable). Results: Ten studies including 18,053 subjects were finally included in this meta-analysis. In our pooled analysis, compared to CAD patients with the lowest RLP-C category, the CAD patients with the highest RLP-C category had a significantly higher risk of future MACEs during follow-up (HR 1.79, 95% CI, 1.42−2.26, I2 = 60.31%, p < 0.01), which was consistent with outcomes of meta-analysis with the RLP-C analyzed as a continuous variable (HR 1.40, 95% CI, 1.28−1.53, I2 = 38.20%, p < 0.01). The sensitivity analysis confirmed the robustness of the results, and no significant publication bias was identified. Conclusion: The present meta-analysis suggests that the RLP-C was associated with an increased risk of long-term MACEs in patients with CAD at baseline. It is necessary to conduct randomized controlled trials to explore whether reducing the RLP-C level is conducive to reducing residual cardiovascular risk, even coronary plaque regression.

Clopidogrel versus ticagrelor in East Asian patients aged 75 years or older with acute coronary syndrome: observations from the GF-APT registry.

The benefits of potent antithrombotic therapy usually come at the expense of a higher risk of bleeding. The efficacy and safety of ticagrelor in elderly East Asian populations remains debated due to the concerns about the imbalance of ischemic and bleeding risks. This study aimed to compare the impact of clopidogrel with ticagrelor on clinical outcomes in East Asian patients aged ≥75 years with acute coronary syndrome (ACS) using data from an institutional registry. We assessed the treatment effect of ticagrelor versus clopidogrel based on propensity scores and multivariate Cox proportional hazards models. A total of 2775 ACS patients were included, of which 235 (8.5%) were treated with ticagrelor. The primary efficacy outcome occurred in 11.9% of patients treated with ticagrelor versus 8.8% treated with clopidogrel. There was no significant association between treatment with ticagrelor and a lower risk of the primary efficacy outcome (p = .156). However, the incidences of all-cause death (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.02 to 2.79) and major bleeding (adjusted HR 2.20, 95% CI 1.06 to 4.56) were significantly higher in patients treated with ticagrelor than clopidogrel. In elderly patients with ACS from East Asia, the efficacy of clopidogrel was comparable to ticagrelor, while ticagrelor is associated with an increased risk of mortality and major bleeding.

What is the context?Current guidelines recommend ticagrelor over clopidogrel for patients with acute coronary syndrome (ACS).There are no specific guidelines concerning the elderly, and data on optimal antiplatelet therapy in elderly are quite scarce.Further study was necessary to identify the efficacy and safety of ticagrelor and clopidogrel in elderly patients from East Asian populations which are reported to be at a higher risk of bleeding.What is new?The risk of major adverse cardiac events did not differ significantly between clopidogrel versus ticagrelor in patients aged ≥75 years from East Asia, while the use of ticagrelor might be associated with increased risk of mortality and major bleeding events.Analyses after propensity score matching showed consistent results on the safety and efficacy of clopidogrel versus ticagrelor.The benefit of potent P2Y₁₂ inhibitor ticagrelor over clopidogrel is questionable in elderly East Asian patients with ACS.What is the impact? This study provides more information on the use of potent antiplatelet therapy in older patients from Asia. The individual assessment of ischemic and bleeding risk is necessary to guide decision-making on DAPT rather than applying the recommendations of guidelines directly.

Photocatalytic Synthesis of Sulfinamides and Sulfoxides from Nitroarenes and Thiophenols.

We present an efficient and versatile visible light-driven methodology for synthesizing sulfinamides and sulfoxides using nitroarenes as the nitrogen source and thiophenols as the sulfur source. The switch-over of the two reaction pathways was achieved by changing the type of photocatalyst and the amount of thiophenol in the reaction mixture. The reaction proceeds under mild conditions with good functional group tolerance and can easily be scaled up.

LincRNA-EPS increases TGF-ß expression to inhibit the Wnt/ß-catenin pathway, VSMC osteoblastic differentiation and vascular calcification in diabetic mice.

In patients with diabetes, the Wnt/ß-catenin pathway in vascular smooth muscle cells (VSMCs) is continuously activated by low-intensity inflammation, which leads to the osteoblastic differentiation of these cells and the deposition of calcium and phosphorus in blood vessels. The aim of the present study was to determine whether long intergenic non-coding RNA-erythroid pro-survival (lincRNA-EPS) was able to ameliorate vascular calcification (VC) associated with diabetes. VSMCs isolated from C57BL/6 mice were transfected with lincRNA-EPS overexpression vector in vitro and their osteoblastic differentiation was evaluated under high-glucose conditions. In addition, a mouse model of diabetes was established, which included a lincRNA-EPS knockout group and a lincRNA-EPS high expression group. Blood vessel samples from the mice were examined to determine the degree of calcification. The levels of inflammatory factors in serum were also detected. The VSMCs transfected with lincRNA-EPS overexpression vector exhibited less osteoblastic differentiation and migration and significantly lower levels of Wnt pathway-associated proteins than those transfected with empty control. Furthermore, the in vivo experiments revealed that the overexpression of lincRNA-EPS significantly reduced VC in diabetic mice. Therefore, on the basis of these findings, it is suggested that lincRNA-EPS overexpression may provide a novel and effective method for the treatment of VC in patients with diabetes.

Long-term safety and absorption assessment of a novel bioresorbable nitrided iron scaffold in porcine coronary artery.

This study aimed to investigate the long-term biocompatibility, safety, and degradation of the ultrathin nitrided iron bioresorbable scaffold (BRS) in vivo, encompassing the whole process of bioresorption in porcine coronary arteries. Fifty-two nitrided iron scaffolds (strut thickness of 70 µm) and 28 Vision Co-Cr stents were randomly implanted into coronary arteries of healthy mini-swine. The efficacy and safety of the nitrided iron scaffold were comparable with those of the Vision stentwithin 52 weeks after implantation. In addition, the long-term biocompatibility, safety, and bioresorption of the nitrided iron scaffold were evaluated by coronary angiography, optical coherence tomography, micro-computed tomography, scanning electron microscopy, energy dispersive spectrometry and histopathological evaluations at 4, 12, 26, 52 weeks and even at 7 years after implantation. In particular, a large number of struts were almost completely absorbed in situ at 7 years follow-up, which were first illustrated in this study. The lymphatic drainage pathway might serve as the potential clearance way of iron and its corrosion products.

Metal- and Strain-Free Bioorthogonal Cycloaddition of o-Diones with Furan-2(3H)-one as Anionic Cycloaddend.

The development of new bioorthogonal reactions with mutual orthogonality to classic bioorthogonal reactions such as the strain-promoted azide-alkyne click reaction and the inverse-electron-demand Diels-Alder reaction is of great importance in providing chemical tools for multiplex labelling of live cells. Here we report the first anionic cycloaddend-promoted bioorthogonal cycloaddition reaction between phenanthrene-9,10-dione and furan-2(3H)-one derivatives, where the high polarity of water is exploited to stabilize the highly electron-rich anionic cycloaddend. The reaction is metal- and strain-free, which proceeds rapidly in aqueous solution and on live cells with a second-order rate constant up to 119 M-1 s-1 . The combined utilization of this reaction together with the two other widely used bioorthogonal reactions allows for mutually orthogonal labelling of three types of proteins or three groups of living cells in one batch without cross-talking. Such results highlight the great potential for multiplex labelling of different biomolecules in live cells.

Contemporary sex differences in mortality among patients with ST-segment elevation myocardial infarction: a systematic review and meta-analysis.

OBJECTIVES: To assess the effect of sex differences on short-term and long-term mortality among patients with ST-segment elevation myocardial infarction (STEMI). DESIGN: Systematic review and meta-analysis of contemporary available evidence. SETTING: PubMed, Embase and Cochrane Library were searched for relevant studies reporting sex-specific outcomes among patients with STEMI published between 1 January 2010 and 1 August 2020. Risk ratios (RRs) and 95% CIs were measured using DerSimonian and Laird random-effects model. Sensitivity analyses were performed and publication bias was also checked. All statistical analyses were performed using STATA V.15.0. PARTICIPANTS: Studies providing data about short-term or long-term mortality stratified by sex in patients with STEMI were included. Only study conducted in last 10 years were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was all-cause death at short-term (in-hospital or 30 days) and long-term (at least 12 months) follow-up. RESULTS: A total of 15 studies involving 128 585 patients (31 706 (24.7%) female and 96 879 (75.3%) male) were included. In the unadjusted analyses, female were at a higher risk of short-term mortality (RR, 1.73; 95% CI 1.53 to 1.96, p<0.001, I2=77%) but not long-term mortality (RR, 1.23; 95% CI 0.89 to 1.69, p=0.206, I2=77.5%). When adjusted effect estimates from individual studies were used in meta-analysis, the association between female and higher risk of short-term mortality remained significant (RR, 1.24; 95% CI 1.11 to 1.38, p<0.001, I2=39.6%). And adjusted long-term mortality was also similar between female and male (RR, 1.11; 95% CI 0.42 to 1.80, p=0.670, I2=74.5%). CONCLUSIONS: An increased short-term but not long-term mortality was found in female with STEMI. After adjustment for baseline cardiovascular risk factors and clinical profiles, short-term mortality remains higher in female with STEMI compared with male, indicating the need for further improvements in management in female patients.

Programmable dual responsive system reconstructing nerve interaction with small-diameter tissue-engineered vascular grafts and inhibiting intimal hyperplasia in diabetes.

Small-diameter tissue-engineered vascular grafts (sdTEVGs) with hyperglycemia resistance have not been constructed. The intimal hyperplasia caused by hyperglycemia remains problem to hinder the patency of sdTEVGs. Here, inspired by bionic regulation of nerve on vascular, we found the released neural exosomes could inhibit the abnormal phenotype transformation of vascular smooth muscle cells (VSMCs). The transformation was a prime culprit causing the intimal hyperplasia of sdTEVGs. To address this concern, sdTEVGs were modified with an on-demand programmable dual-responsive system of ultrathin hydrogels. An external primary Reactive Oxygen Species (ROS)-responsive Netrin-1 system was initially triggered by local inflammation to induce nerve remolding of the sdTEVGs overcoming the difficulty of nerve regeneration under hyperglycemia. Then, the internal secondary ATP-responsive DENND1A (guanine nucleotide exchange factor) system was turned on by the neurotransmitter ATP from the immigrated nerve fibers to stimulate effective release of neural exosomes. The results showed nerve fibers grow into the sdTEVGs in diabetic rats 30 days after transplantation. At day 90, the abnormal VSMCs phenotype was not detected in the sdTEVGs, which maintained long-time patency without intima hyperplasia. Our study provides new insights to construct vascular grafts resisting hyperglycemia damage.

Ticagrelor vs. Clopidogrel After Complex Percutaneous Coronary Intervention in Patients With Stable Coronary Artery Disease.

Background: Patients undergoing complex percutaneous coronary intervention (PCI) have an increased risk of cardiovascular events. Whether potent antiplatelet therapy after complex PCI improves outcomes in patients with stable coronary artery disease (SCAD) remains unclear. Objectives: To assess the efficacy and safety of ticagrelor vs. clopidogrel in patients with SCAD undergoing complex PCI. Methods: Patients with a diagnosis of SCAD and undergoing PCI during January 2016 to December 2018 were selected from an institutional registry. The primary efficacy endpoint was major adverse cardiac events (MACE) within 12 months after PCI. The primary safety endpoint was major bleeding. Results: Among 15,459 patients with SCAD included in this analysis, complex PCI was performed in 6,335 (41.0%) patients. Of patients undergoing complex PCI, 1,123 patients (17.7%) were treated with ticagrelor. The primary efficacy outcome after complex PCI occurred in 8.6% of patients in the ticagrelor group and 11.2% in the clopidogrel group. Compared with clopidogrel, ticagrelor decreased the risk of MACE in patients undergoing complex PCI [adjusted hazard ratio (HR): 0.764; 95% confidence interval (CI): 0.615 to 0.949; p = 0.015], but not in non-complex PCI (p for interaction = 0.001). There was no significant difference in incidence of major bleeding between patients treated with ticagrelor and clopidogrel (p = 0.221), while ticagrelor was associated with an increased risk of minor bleeding (adjusted HR: 3.099; 95% CI: 2.049 to 4.687; p < 0.001). Conclusion: In patients with SCAD and undergoing complex PCI, ticagrelor could substantially reduce the risk of adverse cardiovascular outcomes without increasing the risk of major bleeding compared with clopidogrel.

Prognostic value of GRACE and CHA2DS2-VASc score among patients with atrial fibrillation undergoing percutaneous coronary intervention.

AIMS: The GRACE and CHA2DS2-VASc risk score are developed for risk stratification in patients with acute coronary syndrome and AF, respectively. We aimed to assess the predictive performance of the GRACE score and CHA2DS2-VASc score among patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). METHODS: Consecutive patients with a diagnosis of AF admitted to our hospital for PCI between January 2016 and December 2018 were included and followed up for at least 1 year. The primary endpoint was a composite of major adverse cardiac events (MACEs) including all-cause mortality, repeat revascularization, myocardial infarction, or ischaemic stroke. RESULTS: A total of 1452 patients were identified. Cox regression demonstrated that the GRACE (HR 1.014, 95% CI 1.008-1.020, p < 0.001) but not the CHA2DS2-VASc score was associated with the risk of MACEs. Both GRACE and CHA2DS2-VASc scores were predictive of all-cause mortality with HR of 1.028 (95% CI 1.020-1.037, p < 0.001) and 1.334 (95% CI 1.107-1.632, p = 0.003). Receiver operating characteristic analyses showed both scores had similar discrimination capacity for all-cause mortality (C-statistic: 0.708 for GRACE vs. 0.661 for CHA2DS2-VASc, p = 0.299). High GRACE score was also significantly associated with increased risk of ischaemic stroke (HR 1.018, 95% CI 1.005-1.031, p = 0.006) and major bleeding (HR 1.012, 95% CI 1.001-1.024, p = 0.039), whereas high CHA2DS2-VASc score was not. CONCLUSIONS: High GRACE score but not CHA2DS2-VASc score were both associated with an increased risk of MACEs after PCI in patients with AF. The GRACE and CHA2DS2-VASc scores have similar predictive performance for predicting all-cause mortality.Key messages:In patients with AF undergoing PCI, increasing GRACE but not CHA2DS2-VASc scores was independently associated high risk of MACEs.The GRACE score could also help identify patients at higher risk of stroke and major bleeding.Both GRACE and CHA2DS2-VASc scores showed good ability in the prediction of all-cause mortality.

Visible Light Induced Reduction and Pinacol Coupling of Aldehydes and Ketones Catalyzed by Core/Shell Quantum Dots.

We present an efficient and versatile visible light-driven methodology to transform aryl aldehydes and ketones chemoselectively either to alcohols or to pinacol products with CdSe/CdS core/shell quantum dots as photocatalysts. Thiophenols were used as proton and hydrogen atom donors and as hole traps for the excited quantum dots (QDs) in these reactions. The two products can be switched from one to the other simply by changing the amount of thiophenol in the reaction system. The core/shell QD catalysts are highly efficient with a turn over number (TON) larger than 4 × 104 and 4 × 105 for the reduction to alcohol and pinacol formation, respectively, and are very stable so that they can be recycled for at least 10 times in the reactions without significant loss of catalytic activity. The additional advantages of this method include good functional group tolerance, mild reaction conditions, the allowance of selectively reducing aldehydes in the presence of ketones, and easiness for large scale reactions. Reaction mechanisms were studied by quenching experiments and a radical capture experiment, and the reasons for the switchover of the reaction pathways upon the change of reaction conditions are provided.

The relationship between residual cholesterol risk and plaque characteristics in patients with acute coronary syndrome: Insights from an optical coherence tomography study.

BACKGROUND AND AIMS: The impact of residual cholesterol risk (RCR) on plaque characteristics is not fully understood. The study aims to explore the relationship between RCR and plaque features in patients presenting with acute coronary syndrome (ACS). METHODS: All ACS patients undergoing pre-intervention optical coherence tomography (OCT) with high-sensitivity C-reactive protein (hs-CRP) <2 mg/L on admission were retrospectively enrolled from January to December 2017, at Beijing Anzhen Hospital, Capital Medical University. RCR was defined as low density lipoprotein cholesterol (LDL-C) ≥1.8 mmol/L. Patients were divided into the RCR and non-RCR groups according to baseline LDL-C. RESULTS: A total of 90 patients (94 vessels) were included, with 50 in the RCR group and 40 in the non-RCR group, respectively. Compared with the non-RCR group, patients in the RCR group were younger (54.0 ± 11.04 vs. 58.4 ± 9.59, p = 0.049) and had a higher incidence of multivessel disease (6.0% vs. 2.5%, p = 0.028). With regard to plaque characteristics, fibrous plaque (0.0% vs 12.5%, p = 0.003) was less and fibroatheroma (79.6% vs. 50.0%, p = 0.028) was more frequently seen in the RCR group. Patients in the RCR group were more prone to present with plaque rupture (24.1% vs 5.0%, p = 0.008). Cholesterol crystal (22.2% vs 12.5%, p = 0.226) and thin-cap fibroatheroma (25.9% vs. 12.5%, p = 0.109) were more common in the RCR group, though without statistical difference. Multivariate logistic regression showed that RCR (odds ratio [OR]: 7.95, p = 0.011) and smoking (OR: 4.08, p = 0.026) were independent risk factors of plaque rupture in our patients. CONCLUSIONS: ACS patients with RCR are more likely to have atherosclerotic plaque and plaque rupture, indicating a more vulnerable plaque phenotype.

Efficacy and Safety of Transcatheter vs. Surgical Aortic Valve Replacement in Low-to-Intermediate-Risk Patients: A Meta-Analysis.

Background: The efficacy and safety of transcatheter aortic-valve replacement (TAVR) vs. surgical aortic valve replacement (SAVR) for low- to intermediate-surgical risk patients remains uninvestigated. Objectives: We aimed to investigate the efficacy and safety of transcatheter aortic-valve replacement (TAVR) vs. surgical aortic valve replacement (SAVR) for low-intermediate surgical risk patients. Methods: PubMed, Cochrane Library, and Embase databases were searched to identify potential references. Only randomized controlled trials (RCTs) or observational studies using propensity score matching were eligible for screening. The primary endpoint was all-cause death. The secondary outcomes were bleeding, stroke, myocardial infarction (MI), and other complications of aortic-valve replacement. In addition, we performed subgroup analysis based on surgical risk and study type. Results: Eight RCTs and 13 observational studies covering 12,467 patients were included in the current meta-analysis. For patients with low-surgical risk, compared with SAVR, TAVR was found to be associated with a lower mortality at a follow-up period of 1 year (odds ratio, OR: 0.66, 95% CI: [0.46, 0.96], P = 0.03). This benefit disappeared when the follow-up was extended to 2 years (OR: 0.89, 95% CI: [0.61, 1.30], P = 0.56). For patients with intermediate-surgical risk, TAVR showed to have similar mortality with SAVR regardless of follow-up period (30-day, 1-year, or 2-year). TAVR could reduce the incidence of bleeding, AF, and AKI. For complications, such as MI and stroke, TAVR exhibited to have similar safety with SAVR. However, TAVR was found to be associated with a higher incidence of reintervention, major vascular complication, paravalvular leak, and PPI. Conclusion: For patients with a low-to-intermediate surgical risk, TAVR has at least an equivalent clinical effect to SAVR for 2 years after the procedure.

Cardiac Injury and Clinical Course of Patients With Coronavirus Disease 2019.

Background: Cardiac injury is recognized as one of the most common critical complications during exacerbation of coronavirus disease 2019 (COVID-19). This study aimed to investigate the effect of cardiac injury on the clinical course of COVID-19 and to examine its potential mechanism and treatments. Methods and Results: A total of 222 hospitalized patients with COVID-19 from Wuhan were selected for the study during February 10 to March 28, 2020. Demographic, laboratory, and clinical data on admission and during hospitalization were compared between patients with COVID-19 with or without cardiac injury. On admission, cardiac injury (n = 29) was associated with advanced age, more underlying coronary artery disease, and a lower Pao2. Troponin levels were correlated with inflammatory markers (C-reactive protein: r = 0.348, P < 0.001; interleukin 6: r = 0.558, P < 0.001) and d-dimer levels (r = 0.598, P < 0.001). During hospitalization, another six patients suffered from cardiac injury and cardiac injury (n = 35), resulting in higher rates of ventilation (invasive: 51.4 vs. 1.6%, P < 0.001; non-invasive: 31.4 vs. 1.1%, P < 0.001) and mortality (54.3 vs. 1.1%, P < 0.001). Cardiac injury on admission was a predictive factor for mortality (adjusted hazard ratio = 4.73, 95% confidence interval = 1.35-16.63, P = 0.015). Receiver operating characteristic curve analysis showed that, on admission, a troponin level of 36.35 pg/mL was predictive for mortality with a sensitivity of 73.7% and a specificity of 92.1%. Conclusions: Cardiac injury complicates the disease course and increases the mortality rate of COVID-19. Troponin levels should be checked at admission and during hospitalization for triage, better monitoring, and managing those with COVID-19, especially in the most severe patients. Condensed Abstract: Cardiac injury is not uncommon in COVID-19. In a cohort of 222 patients with COVID-19, cardiac injury was found in 29 patients on admission and in another 6 patients during hospitalization. The admission level of troponin was well-correlated with inflammatory factors and d-dimer levels and strongly predicted mortality. Cardiac injury is a manifestation secondary to hypoxia and systemic infection, but which nevertheless further complicates the disease course and increases the mortality rate. Troponin levels should be checked at admission and during hospitalization for triage, better monitoring, and managing those with COVID-19, especially in the most severe patients.

Sodium-glucose cotransporter 2 inhibitors and fracture risk in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fracture compared with those without T2DM. Some oral glucose-lowering agents may increase the incidence of fracture. Whether sodium-glucose co-transporter 2 inhibitors (SGLT2is) are associated with increased risk of fracture remains unclear. METHODS: We retrieved articles from PubMed, Embase, Cochrane Library database, and other sources up to 24 October 2019. We included randomized controlled trials (RCTs) that reported fractures and analyzed the fracture incidence of SGLT2i, canagliflozin, dapagliflozin, and empagliflozin. Subgroup analysis was also performed based on baseline characteristics. RESULTS: A total of 78 RCTs with 85,122 patients were included in our analysis. The overall SGLT2i fracture incidence was 2.56% versus 2.77% in the control group [odds ratio (OR), 1.03; 95% confidence interval (CI) (0.95, 1.12); p = 0.49]. Compared with the control treatment, treatment with canagliflozin led to a higher rate of fractures [OR, 1.17; 95% CI (1.00, 1.37); p = 0.05], but no significant difference was observed when compared with dapagliflozin [OR, 1.02; 95% CI (0.90, 1.15); p = 0.79] or empagliflozin [OR, 0.89; 95% CI (0.73, 1.10); p = 0.30]. Subgroup analysis showed that, in a follow-up of less than 52 weeks, SGLT2i decreased the incidence of fracture by 29% [OR, 0.71; 95% CI (0.55, 0.93); p = 0.01], but this benefit was lost when the follow-up extended to more than 52 weeks [OR, 1.08; 95% CI (0.98, 1.18); p = 0.12]. CONCLUSION: Canagliflozin seems to increase the risk of fracture, while other SGLT2is do not result in a higher incidence of fracture.

Ticagrelor Versus Clopidogrel in Patients with Two CYP2C19 Loss-of-Function Alleles Undergoing Percutaneous Coronary Intervention.

PURPOSE: To compare the risk of cardiovascular events between patients with two CYP2C19 loss-of-function alleles who were prescribed ticagrelor or clopidogrel after percutaneous coronary intervention (PCI). METHODS: Patients with two loss-of-function alleles based on the CYP2C19 genotype were selected from patients enrolled in a retrospective institutional registry. Propensity score matching using logistic regression was performed to adjust for bias between patients prescribed ticagrelor or clopidogrel. Multivariate Cox regression was used to compare the risk of adverse events in the ticagrelor and clopidogrel groups. The primary outcome was the incidence of major adverse cardiac events plus any repeat target vessel revascularization within 12 months after PCI. The safety outcomes were minor and major bleeding events. RESULTS: From 1518 patients carrying two loss-of-function alleles based on the CYP2C19 genotype who underwent PCI, 638 patients treated with ticagrelor or clopidogrel were successfully propensity-score matched. The primary outcome occurred in 25 patients (7.8%) in the ticagrelor group and 47 (14.7%) in the clopidogrel group. The risk of the primary outcome was significantly lower in the ticagrelor group versus the clopidogrel group (HR 0.466, 95% CI 0.286-0.759, p = 0.002). The incidence of major bleeding events did not significantly differ between the ticagrelor and clopidogrel groups (0.3% and 0.9%, respectively), while the ticagrelor group had a higher risk of minor bleeding events (HR 1.959, 95% CI 1.396-2.750, p < 0.001). CONCLUSIONS: In patients with two CYP2C19 loss-of-function alleles, ticagrelor was more effective than clopidogrel in preventing cardiovascular events, while the two antiplatelet agents were associated with similar incidences of major bleeding.

The Prognostic Significance of Different Bleeding Classifications in off-pump coronary artery bypass grafting.

BACKGROUND: Perioperative bleeding during cardiac surgery are known to make patients susceptible to adverse outcomes and several bleeding classifications have been developed to stratify the severity of bleeding events. Further validation of different classifications was needed. The aim of present study was to validate and explore the prognostic value of different bleeding classifications in patients undergoing off-pump coronary artery bypass grafting (OPCAB). METHODS: Data on baseline and operative characteristics of 3988 patients who underwent OPCAB in Beijing Anzhen Hospital from February 2008 to December 2014 were available. The primary endpoint was a composite of in-hospital death and nonfatal postoperative myocardial infarction (MI). The secondary endpoint was postoperative acute kidney injury (AKI). We explored the association of major bleeding defined by the European registry of Coronary Artery Bypass Grafting (E-CABG), Universal Definition of Perioperative Bleeding (UDPB), Bleeding Academic Research Consortium (BARC) classification and Study of Platelet Inhibition and Patient Outcomes (PLATO) with primary endpoints by multivariable logistic regression analysis and investigated their significance of adverse event prediction using goodness-of-fit tests of - 2 log likelihood. RESULTS: In-hospital mortality was 1.23% (n = 49) and postoperative MI was observed in 4.76% (n = 190) of patients, AKI in 24.69% (n = 985). The incidence of the primary outcome was 5.99% (n = 239). Multivariable logistic regression analysis showed that BARC type 4 (OR = 2.64, 95% CI: 1.66-4.19, P < 0.001), UDPB class 4 (OR = 3.52, 95% CI: 2.05-6.02, P < 0.001) and E-CABG class 2-3 (class 2: OR = 2.24, 95% CI: 1.36-3.70, P = 0.001; class 3: OR = 12.65, 95% CI: 2.74-18.43, P = 0.002) bleeding but not PLATO bleeding were associated with an increased risk of in-hospital death and postoperative MI. Major bleeding defined by all the four classifications mentioned above was an independent risk factor of AKI after surgery. Inclusion of major bleeding defined by these four classifications improved the predictive performance of the multivariable model with baseline characteristics. CONCLUSIONS: Bleeding assessed by BARC, E-CABG and UDPB classifications were significantly associated with poorer immediate outcomes. These classifications seemed to be valuable tool in the assessment of prognostic effect of perioperative bleeding.