An updated meta-analysis of optimal medical therapy with or without invasive therapy in patients with stable coronary artery disease.

BACKGROUND: The efficacy of optimal medical therapy (OMT) with or without revascularization therapy in patients with stable coronary artery disease (SCAD) remains controversial. We performed a meta-analysis of randomized controlled trials (RCTs) that compared OMT with or without revascularization therapy for SCAD patients. METHODS: Studies were searched in PubMed, EMBASE, and the Cochrane Central Register of Clinical Trials from January 1, 2005, to December 30, 2023. The main efficacy outcome was a composite of all-cause death, myocadiac infarction, revascularization, and cerebrovascular accident. Results were pooled using random effects model and fixed effects model and are presented as odd ratios (ORs) with 95% confidence intervals (CI). RESULTS: Ten studies involving 12,790 participants were included. The arm of OMT with revascularization compared with OMT alone was associated with decreased risks for MACCE (OR 0.55 [95% CI 0.38-0.80], I²=93%, P = 0.002), CV death (OR 0.84 [95% CI 0.73-0.97], I²=36%, P = 0.02), revascularization (OR 0.32 [95% CI 0.20-0.50], I²=92%, P < 0.001), and MI (OR 0.85 [95% CI 0.76-0.96], I²=45%, P = 0.007). While there was no significant difference between OMT with revascularization and OMT alone in the odds of all-cause death (OR 0.94 [95% CI 0.84-1.05], I²=0%, P = 0.30). CONCLUSIONS: The current updated meta-analysis of 10 RCTs shows that in patients with SCAD, OMT with revascularization would reduce the risk for MACCE, cardiovascular death, and MI. However, the invasive strategy does not decrease the risks for all-cause mortality when comparing with OMT alone.

Efficacy and Safety of Direct Oral Anticoagulants in Pediatric Venous Thromboembolism: A Systematic Review and Meta-Analysis.

OBJECTIVES: To assess the efficacy and safety of direct oral anticoagulants (DOACs) in comparison to standard-of-care (SOC) anticoagulants in the management and prophylaxis of thromboembolic events in pediatric populations. METHODS: A comprehensive search of electronic databases was conducted to identify relevant studies published between January 1, 2015, and December 18, 2022. A meta-analysis was undertaken to evaluate the effect of DOACs on clinically significant endpoints, employing trial-level data with harmonized endpoint definitions. The primary outcome was venous thromboembolism (VTE). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The study was registered with INPLASY (2022120065). RESULTS: Three studies encompassing 934 subjects were included. The incidence of VTE was reduced in patients administered DOACs compared to those on SOC anticoagulants (OR 0.41 [95% CI 0.19-0.93], I² = 0%, P = 0.03). No significant differences were observed between the DOAC and SOC groups in all-cause mortality (OR 0.50 [95% CI 0.07-3.59], I² = 0%, P = 0.35) or serious adverse events (OR 0.75 [95% CI 0.50-1.12], I² = 0%, P = 0.16). The risk of major bleeding (OR 0.50 [95% CI 0.13-1.87], I² = 44%, P = 0.30) and clinically relevant non-major bleeding (OR 1.23 [95% CI 0.50-3.00], I² = 0%, P = 0.65) exhibited no significant differences between the groups. CONCLUSIONS: DOACs are associated with a reduced risk of VTE in pediatric patients without increasing the risk of bleeding, all-cause mortality, or serious adverse events when compared to SOC anticoagulants. DOACs may be an alternative for the treatment and prevention of thromboembolic events in the pediatrics.

Association between P2Y12 inhibitor reloading and in-hospital outcomes for patients with non-ST-segment elevation acute coronary syndrome already on chronic P2Y12 receptor inhibitors therapy in China: findings from the CCC-ACS (improving care for cardiovascular disease in China-acute coronary syndrome) project.

BACKGROUND: The association between P2Y12 receptor inhibitors reloading and in-hospital outcomes in non-ST-segment elevation acute coronary syndrome (NSTEACS) patients who were on chronic P2Y12 receptor inhibitors therapy remained underdetermined. METHODS: The Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS project) is a national registry active from November 2014 to December 2019. 4790 NSTEACS patients on chronic P2Y12 receptor inhibitors therapy were included. Cox proportional hazard models, Kaplan-Meier curves, and subgroup analyses were conducted. RESULTS: The NSTEACS patients who received reloading of P2Y12 receptor inhibitors were younger and had fewer comorbid conditions. The reloading group had a lower risk of major adverse cardiac events (MACE) (0.51% vs. 1.43%, P = 0.007), and all-cause death (0.36% vs. 0.99%, P = 0.028), the risks of myocardial infarction and major bleeding were not significantly different between patients with and without reloading. In survival analysis, a lower cumulative risk of MACE could be identified (Log-rank test, P = 0.007) in reloading group. In the unadjusted Cox model, reloading P2Y12 receptor inhibitors was associated with a decreased risk of MACE [HR, 0.35; 95% CI 0.16-0.78; (P = 0.010)] and all-cause death [HR, 0.37; 95% CI 0.14-0.94; (P = 0.036)]. Reloading of P2Y12 receptor inhibitors was associated with a decreased risk of MACE in most of the subgroups. CONCLUSIONS: In NSTEACS patients already taking P2Y12 receptor inhibitors, we observed a decreased risk of in-hospital MACEs and all-cause mortality and did not observe an increased risk of major bleeding, with reloading. The differential profile in the two groups might influence this association and further studies are warranted. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov (Unique identifier: NCT02306616, date of first registration: 03/12/2014).

Sodium-glucose co-transporter 2 inhibitors in heart failure with mildly reduced or preserved ejection fraction: an updated systematic review and meta-analysis.

OBJECTIVES: Heart failure with mildly reduced ejection fraction (HFmrEF)  or  heart failure with preserved ejection fraction (HFpEF)  are associated with significant morbidity and mortality, as well as growing health and economic burden. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are very promising for the outcome improvement of patients with HFpEF or HFmrEF. The meta-analysis was performed to investigate the effects of SGLT2 inhibitors in HFpEF or  HFmrEF, by pooling data from all clinically randomized controlled trials (RCTs) available to increase power to testify. METHODS: Studies were searched in electronic databases from inception to November, 2022. We performed a meta-analysis to estimate the effect of SGLT2 inhibitors on clinical endpoints in patients with HFpEF or HFmrEF, using trial-level data with consistent endpoint definitions. The primary outcome was the composite of heart failure (HF) hospitalization or cardiovascular death. Hazard ratio (HR) was pooled with 95% confidence interval (CI) for dichotomous data. This study was registered with INPLASY 2022110095. RESULTS: Six studies involving 15,989 participants were included into the final analysis. Pooled analyses revealed that SGLT2 inhibitors significantly reduced the composite of HF hospitalization or cardiovascular death [HR: 0.79 (0.72-0.85); I2 = 0%; P < 0.00001] and HF hospitalizations [HR: 0.74 (0.67-0.82); I2 = 0%; P < 0.00001]. This finding was seen in both HFmrEF trials [HR: 0.76 (0.67-0.87); I2 = 49%; P < 0.0001] and HFpEF subgroup studies [HR: 0.70 (0.53-0.93); I2 = 0%; P = 0.01]. The incidence of any serious adverse events [OR: 0.89 (0.83-0.96); I2 = 0%; P = 0.002] was significantly lower in the SGLT2 inhibitor arm. No significant differences were observed between the two groups with regard to cardiovascular death and all-cause death. CONCLUSIONS: This meta-analysis of patients with heart failure of left ventricular ejection fraction (LVEF) > 40% showed that SGLT2 inhibitors significantly reduce the risk of  the composite of cardiovascular death and hospitalization for heart failure, but not cardiovascular death and all-cause death. Nevertheless, given that SGLT2 inhibitors may reduce the risk of hospitalization for heart failure, they should be considered the fundamental treatment for all patients with HFpEF or  HFmrEF.

The Compound Effect of Spatial and Temporal Resolutions on the Accuracy of Urban Flood Simulation.

Flood disaster is one of the critical threats to cities. With the intellectualization tendency of Industry 4.0, refined urban flood models can effectively reproduce flood inundation scenarios and support the decision-making on the response to the flood. However, the spatiotemporal variability of rainfall and the spatial heterogeneity of the surface greatly increase the uncertainties in urban flood simulations. Therefore, it is crucial to account for spatiotemporal variability of rainfall events and grids of the model as accurately as possible to avoid misleading simulation results. This study aims to investigate the effect of temporal resolutions of rainfall and spatial resolutions of the model on urban flood modeling in small urban catchments and to explore a proper combination of spatiotemporal schemes. The IFMS Urban (integrated flood modeling system, urban) is used to construct a one-dimension and two-dimension coupled urban flood model in the typical inundated area in Dongguan, China. Based on five temporal resolutions of rainfall input and four spatial resolutions, the compound effect of spatiotemporal resolutions on the accuracy of urban flood simulations is systematically analyzed, and the variation characteristics are investigated. The results show that the finer the temporal resolution is, the higher the simulation accuracy of the maximum inundated water depth. Considering the spatial resolution, as the spatial grid becomes smaller, the relative error of the maximum inundated water depth decreases, but it also shows some nonlinear characteristics. Therefore, the smaller grid does not always mean a better simulation. The spatial resolution has a greater impact on the flood simulation accuracy than the temporal resolution. The simulation performance reaches the best when the grid interval is 100 m and the rainfall input interval is 5 min, 10 min, or 15 min. Affected by other factors such as terrain slope, the simulation accuracies under different spatiotemporal resolutions present complex nonlinear characteristics. The mechanisms of the compound effect of the spatiotemporal resolutions on the model simulation and the effect of underlying surface and topography on model simulation will be the focus of in-depth exploration for the future urban flood model.

Development and Validation of a Nomogram for Predicting the Risk of Adverse Cardiovascular Events in Patients with Coronary Artery Ectasia.

Coronary artery ectasia (CAE) is a rare finding and is associated with poor clinical outcomes. However, prognostic factors are not well studied and no prognostication tool is available. In a derivation set comprising 729 consecutive CAE patients between January 2009 and June 2014, a nomogram was developed using Cox regression. Total of 399 patients from July 2014 to December 2015 formed the validation set. The primary outcome was 5-year major adverse cardiovascular events (MACE), a component of cardiovascular death and nonfatal myocardial infarction. Besides the clinical factors, we used quantitative coronary angiography (QCA) and defined QCA classification of four types, according to max diameter (< or ≥5 mm) and max length ratio (ratio of lesion length to vessel length, < or ≥1/3) of the dilated lesion. A total of 27 cardiovascular deaths and 41 nonfatal myocardial infarctions occurred at 5-year follow-up. The nomogram effectively predicted 5-year MACE risk using predictors including age, prior PCI, high sensitivity C-reactive protein, N-terminal pro-brain natriuretic peptide, and QCA classification (area under curve [AUC] 0.75, 95% CI 0.68-0.82 in the derivation set; AUC 0.71, 95% CI 0.56-0.86 in the validation set). Patients were classified as high-risk if prognostic scores were ≥155 and the Kaplan-Meier curves were well separated (log-rank p < 0.001 in both sets). Calibration curve and Hosmer-Lemeshow test indicated similarity between predicted and actual 5-year MACE survival (p = 0.90 in the derivation and p = 0.47 in the validation set). This study developed and validated a simple-to-use method for assessing 5-year MACE risk in patients with CAE.

Improving the robustness of beach water quality modeling using an ensemble machine learning approach.

Microbial pollution of beach water can expose swimmers to harmful pathogens. Predictive modeling provides an alternative method for beach management that addresses several limitations associated with traditional culture-based methods of assessing water quality. Widely-used machine learning methods often suffer from high variability in performance from one year or beach to another. Therefore, the best machine learning method varies between beaches and years, making method selection difficult. This study proposes an ensemble machine learning approach referred to as model stacking that has a two-layered learning structure, where the outputs of five widely-used individual machine learning models (multiple linear regression, partial least square, sparse partial least square, random forest, and Bayesian network) are taken as input features for another model that produces the final prediction. Applying this approach to three beaches along eastern Lake Erie, New York, USA, we show that generally the model stacking approach was able to generate reliably good predictions compared to all of the five base models. The accuracy rankings of the stacking model consistently stayed 1st or 2nd every year, with yearly-average accuracy of 78%, 81%, and 82.3% at the three studied beaches, respectively. This study highlights the value of the model stacking approach in predicting beach water quality and solving other pressing environmental problems.

The beneficial effects of renin-angiotensin system blockades on 2 year outcomes in coronary artery ectasia patients.

OBJECTIVES: This study was designed to investigate the impact of renin-angiotensin system blockade (RASB) therapy with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on the outcomes of coronary artery ectasia (CAE). METHODS: The CAE patients identified by coronary angiography from our center were consecutively enrolled. We obtained the baseline discharge prescription of RASB from the medical records system and conducted follow-up through telephone interviews. Cox regression models, propensity score and subgroup analysis were used to assess the impact of RASB on all-cause mortality and non-fatal myocardial infarction. Both the unadjusted and adjusted Kaplan-Meier curves stratified by RASB therapy were plotted. RESULTS: There were 595 patients with CAE in total and 333 (56.0%) were prescribed RASB therapy. Over a 2 year follow-up time, 16 all-cause deaths and 10 non-fatal myocardial infarctions were identified. Those patients treated with RASB had a significantly lower all-cause mortality and non-fatal myocardial infarction rate with an adjusted hazard ratio of 0.32 (95% confidence interval: 0.13 to 0.77, p = .011). The outcome benefits of RASB therapy were further confirmed in the propensity score analysis and subgroup analysis. CONCLUSIONS: This observational study suggests that RASB therapy is associated with a lower risk of all-cause mortality and non-fatal myocardial infarction in patients with CAE.

Independent Prognostic Value of High-sensitivity C-reactive Protein in Patients with Coronary Artery Ectasia.

BACKGROUND: Despite its severity, coronary artery ectasia (CAE) is still poorly understood. High-sensitivity C-reactive protein (hs-CRP) has been recognized as a prognostic factor in some cardiovascular diseases but not assessed in CAE. The aim of this observational study was to investigate the prognostic value of hs-CRP in CAE. METHODS: Our analysis evaluated the effect of the baseline hs-CRP on cardiovascular events (CVs) (cardiac death and nonfetal myocardial infarction) in consecutively enrolled stable CAE patients. We used the Cox proportional hazards regression models to examine the association between baseline hs-CRP level and follow-up CVs in CAE. The net reclassification improvement and integrated discrimination improvement (IDI) of hs-CRP were also assessed. RESULTS: We obtained the follow-up results of 540 patients over a median follow-up period of 36 (37.41 ± 15.88) months. The multivariable Cox analysis showed that the hs-CRP was a significant predictor of adverse outcomes in CAE (hazard ratio [HR]: 2.99, 95% confidence interval [CI]: 1.31-6.81, P = 0.0091). In Kaplan-Meier analysis, the group with hs-CRP >3 mg/L had a lower cumulative 66-month event-free survival rate (log-rank test for trend, P = 0.0235) and a higher risk of CVs (HR = 2.66, 95% CI: 1.22-5.77, P = 0.0140) than the group with hs-CRP ≤3 mg/L. Hs-CRP added predictive information beyond that given by the baseline model comprising the classical risk factors (P value for IDI = 0.0330). CONCLUSIONS: A higher level of hs-CRP was independently associated with cardiac death and nonfatal myocardial infarction in CAE patients. The hs-CRP level may therefore provide prognostic information for the risk stratification of CAE patients.