Safety outcomes of sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes and other risk factors for cardiovascular disease: a systematic review and meta-analysis.

Sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) have emerged as standard therapy for heart failure. We aim to assess the safety of SGLT2-Is in patients with a high risk of cardiovascular disease. Areas covered: An electronic database search was conducted for randomized control trials comparing SGLT2-Is to placebo in patients with a high risk of cardiac disease or heart failure. Data were pooled for outcomes using random-effect models. The odds ratio (OR) and 95% confidence interval (CI) were used to compare eight safety outcomes between the two groups. The analysis included ten studies with 71 553 participants, among whom 39 053 received SGLT2-Is; 28 809 were male and 15 655 were female (mean age, 65.2 years). The mean follow-up period was 2.3 years with the range being 0.8-4.2 years. The SGLT2-Is group had a significant reduction in AKI (OR = 0.8;95% CI 0.74-0.90) and serious adverse effects (OR = 0.9; 95% CI 0.83-0.96) as compared to placebo. No difference was found in fracture (OR = 1.1; 95% CI 0.91-1.24), amputation (OR = 1.1; 95% CI 1.00-1.29), hypoglycemia (OR 0.98;95% CI 0.83-1.15), and UTI (OR = 1.1; 95% CI 1.00-1.22). In contrast, DKA (OR = 2.4; 95% CI 1.65-3.60) and volume depletion (OR = 1.2; 95% CI 1.07-1.41) were higher in SGLT2-Is group. Expert opinion/commentary: The benefits of SLGT2-Is outweigh the risk of adverse events. They may reduce the risk of AKI but are associated with an increased risk of DKA and volume depletion. Further studies are warranted to monitor a wider range of safety outcomes of SGLT2-Is.

Outcomes of Mechanical Thrombectomy Compared With Systemic Thrombolysis in Pulmonary Embolism: A Comprehensive Evaluation From the National Inpatient Sample Database.

BACKGROUND: Systemic thrombolysis (ST) may not be ideal for many patients with acute pulmonary embolism (PE) due to bleeding risk. In this analysis, we evaluated the safety and effectiveness of mechanical thrombectomy (MT) as an alternative to ST for acute PE. METHODS: Patients aged ≥18 years who underwent MT and/or ST for PE were identified from the National Inpatient Sample database from 2016 to 2017. Patients who underwent catheter-directed thrombolysis were excluded. We compared in-hospital outcomes of both groups in this retrospective study. RESULTS: Of 16 890 patients who received an intervention for acute PE, 1380 (8.2%) received MT and 15 510 (91.8%) received ST. There was no difference in age between both groups. In-hospital mortality was significantly lower in patients who received MT than that in those who received ST (11.9% vs 20.6%, odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.29-0.93, p=0.028). There was no statistically significant difference in terms of periprocedural bleeding, intracranial hemorrhage, and acute kidney injury between the 2 groups (p≥0.608 for all). Patients who received MT had a higher rate of respiratory complications (19.0% vs 11.6%, OR: 1.79, 95% CI: 1.06-3.03, p=0.030) and discharge to an outside facility (34.1% vs 19.2%, OR: 2.18, 95% CI: 1.41-3.37, p<0.001) than those who received ST. CONCLUSION: Mortality was significantly lower with MT than that with ST, but larger randomized studies are needed to validate this. The use of MT should be individualized on the basis of the patients' clinical presentation, risk profile, and local resources. CLINICAL IMPACT: In this study, we utilized the National Inpatient Sample database to study the in-hospital outcomes of pulmonary embolism patients who underwent mechanical thrombectomy compared to those who underwent systemic thrombolysis. We found that the patients who were diagnosed with pulmonary embolism and underwent mechanical thrombectomy had significantly lower mortality compared to those who were treated using systemic thrombolysis. This study was the first of its kind, utilizing the national inpatient sample database for evaluation of mechanical thrombectomy in comparison with the standard of care. These result would direct further randomized controlled trials for better evaluation of the utilization of mechanical thrombectomy in the correct clinical context. Furthermore, our study demonstrated comparable peri-operative complications between the mechanical thrombectomy group and the systemic thrombolysis group. These results would direct clinicians to consider mechanical thrombectomy if clinically indicated given the promising results.

Outcomes of catheter ablation versus antiarrhythmic therapy in patients with atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Recent data have shown an advantage of rhythm control over rate control for the treatment of atrial fibrillation (AF). Nevertheless, the data regarding efficacy of catheter ablation (CA) compared with antiarrhythmic drugs (AADs) in patients with AF is lacking. Therefore, we sought to evaluate recurrence of arrhythmia, all-cause mortality, cardiovascular deaths, stroke/TIA, and all-cause readmissions of CA compared with AAD in patients with AF. METHODS: Systematically searched through PubMed, Google Scholar, EMBASE, and Cochrane for randomized control trials that compared CA and AAD in atrial fibrillation patients. Review Manager 5.4 and OpenMetaAnalyst were used to analyze the data. Data was pooled for the outcomes using random-effect models (DerSimonian and Laird) and reported as pooled odds ratio (OR). RESULTS: A total of 4822 patients were included. The CA group had 2417 patients while the AAD group included 2405 patients. Pooled data demonstrated that the CA arm had a statistically significant decrease in risk for recurrence of arrhythmia as compared to AAD (OR 0.25; [95% CI, 0.18-0.36]; p < 0.001). All-cause readmission was statistically significantly lower in CA as compared to AAD (OR 0.33; [95%CI, 0.17-0.63]; p < 0.001). For other secondary outcomes, there was no statistically significant difference between CA and AAD with regard to all-cause mortality (OR 0.75; [95% CI, 0.55-1.03]), cardiovascular death (OR 0.76; [95% CI, 0.22-2.54]), bleeding (OR 1.09, [95% CI 0.74, 1.61]), or stroke/TIA outcome (OR 0.90, [95% CI, 0.59-1.37]). CONCLUSIONS: In this study of pooled data from 16 RCTs, CA utilization for atrial fibrillation had improved freedom from arrhythmia as well as reduced all-cause readmission compared with AAD.

National outcomes of urgent vs. non-urgent percutaneous edge-to-edge transcatheter mitral valve repair.

Background: The current data regarding outcomes of transcatheter edge-to-edge mitral valve repair with the MitraClip system in the urgent setting has not been well described. Therefore, we sought to evaluate the outcomes of urgent MitraClip procedures compared with non-urgent ones. Method: The Nationwide Inpatient Sample database years 2011-2017 was used to identify hospitalizations for MitraClip in the urgent setting. Propensity score matching was used to compare the patients who underwent MitraClip in urgent versus non-urgent settings. Results: A total of 15,993 patients underwent the MitraClip procedures from 2011 to 2017. 3,929 (24.6%) were urgent and 12,064 (75.4%) were non-urgent. Patients in the urgent group were younger (75.08 vs 77.46) and more likely to be African American (p < 0.001). The urgent group had a higher burden of comorbidities such as diabetes, atrial fibrillation, renal failure and pulmonary circulatory disorders. Using multivariable logistic regression, there was no statistically significant difference in mortality between urgent and non-urgent groups (4.2% vs 1.8%, OR 0.64; 95% CI 0.41-1.00, p = 0.051). Using propensity score matching, there was no statistically significant difference in the in-hospital mortality between urgent and non-urgent groups (4.4% vs 2.8%, OR: 1.60, 95% CI: 0.71-3.63, p = 0.254). The risks of acute kidney injury and discharge to an outside facility were higher in the urgent group (p < 0.001). Conclusion: No significant in-hospital mortality for patients who underwent urgent versus non-urgent MitraClip procedures. Therefore, urgent MitraClip procedure might be an acceptable option when indicated.

Association of Sodium-Glucose Cotransporter 2 Inhibitors With Cardiovascular Outcomes in Patients With Type 2 Diabetes and Other Risk Factors for Cardiovascular Disease: A Meta-analysis.

Importance: The cardiovascular outcome in selected populations when sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) are emerging as standard therapy is not clearly understood. It is important to learn the magnitude of cardiovascular benefit using SGLT2-Is across the select subgroups that include both sexes and multiple age and racial and ethnic groups. Objectives: To evaluate the association between use of SGLT2-Is and cardiovascular benefits in a prespecified group in a larger sample size using data obtained from randomized clinical trials. Data Sources: Search of electronic databases PubMed, Google Scholar, Web of Science, and Cochrane from inception to January 10, 2021, with additional studies identified through conference papers and meeting presentations, ClinicalTrials.gov, and reference lists of published studies. Study Selection: Placebo-controlled randomized clinical trials in which participants had atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD, diabetes, or heart failure and which reported the primary outcome were included in this study. Multicenter observational and nonobservational studies and those with different outcomes of interest were excluded. Data Extraction and Synthesis: Medical Subject Heading search terms included SGLT2-I and multiple cardiovascular outcomes in different combinations. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The analysis of all outcomes was performed using a Mantel-Haenszel equation and the random-effects model. Main Outcomes and Measures: Six efficacy outcomes of SGLT2-I use (cardiovascular death and hospitalization for heart failure [HHF] as the primary outcome and major adverse cardiovascular event, HHF, cardiovascular death, acute myocardial infarction, and all-cause mortality as secondary outcomes), were evaluated. Subgroup analysis was performed for the primary outcome of cardiovascular death or HHF. Odds ratios (ORs) and 95% CIs were used to compare 2 interventions. Results: Ten studies with 71 553 participants were included, among whom 39 053 received SGLT2-Is; among studies that reported these data, 28 809 were men and 15 655 were women (mean age, 65.2 [range, 61.9-70.0] years). Race and ethnicity were defined in the original trials and were categorized as Asian, Black, or other (6900 participants) and White (26 646 participants) for the purposes of this analysis (the category "other" was not specified consistently). In terms of age, 16 793 were younger than 65 years and 17 087 were 65 years or older. At a mean follow-up 2.3 (range, 0.8-4.2) years, the SGLT2-I group favored reduction in primary outcome (3165 of 39 053 [8.10%] vs 3756 of 32 500 [11.56%]; OR, 0.67 [95% CI, 0.55-0.80]; P < .001). No difference was noted in the rate of acute myocardial infarction compared with the placebo group (1256 of 26 931 [4.66%] vs 958 of 20 373 [4.70%]; OR, 0.95 [95% CI, 0.87-1.03]; P = .22). Subgroup analysis favored SGLT2-I use for the primary outcome in both sexes, age groups, and racial and ethnic groups. Conclusions and Relevance: This meta-analysis supports that SGLT2-Is have emerged as an effective class of drugs for improving cardiovascular morbidity and mortality in selected patients. Sodium-glucose cotransporter 2 inhibitors were not associated with reduced risk of acute myocardial infarction. Future long-term prospective studies are warranted to understand the long-term cardiovascular benefits.

End-to-end Modeling for Predicting and Estimating Radiomics: Application to Gray Level Co-occurrence Matrices in CT.

While radiomics models are finding increased use in computer-aided diagnostics and as imaging biomarkers for inference and discovery, their utility in computed tomography (CT) is limited by variability of the image properties produced by different CT scanners, imaging protocols, patient anatomy, and an increasingly diverse range of reconstruction and post-processing software. While these effects can be mitigated with careful data curation and standardization of protocols, this is impractical for diverse sources of image data. In this work, we propose to generalize traditional end-to-end imaging system models to include radiomics calculation as an explicit stage. Such a model permits both prediction of the undesirable variability of radiomics, but also forms a basis for inverting the process to estimate the true underlying radiomics. This framework has the potential to provide for standardization of radiomics across imaging conditions permitting more widespread application of radiomics models; larger, more diverse image databases; and improved diagnoses and inferences based on those standardized metrics. We apply this framework to a large class of popular radiomics based on the Gray Level Co-occurrence matrix under conditions of imaging system that are well describe by traditional linear systems approaches as well as nonlinear systems for which traditional analytic models do not apply.

Standardization of histogram- and gray-level co-occurrence matrices-based radiomics in the presence of blur and noise.

Radiomics have been extensively investigated as quantitative biomarkers that can enhance the utility of imaging studies and aid the clinical decision making process. A major challenge to the clinical translation of radiomics is their variability as a result of different imaging and reconstruction protocols. In this work, we present a novel radiomics standardization framework capable of modeling and recovering the underlying radiomic feature in images that have been corrupted by the effects of spatial resolution and noise. We focus on two classes of radiomics based on pixel value distributions-i.e. histograms and gray-level co-occurrence matrices (GLCMs). We developed a model that predicts these distributions in the presence of system blur and noise, and used that model to invert these physical effects and recover the underlying distributions. Specifically, the effect of blur on histogram and GLCM is highly image-dependent, while additive noise convolves the histogram/GLCM of the noiseless image with those of the noise. The recovery method therefore consists of two deconvolution operations: the first in the image domain to remove the effect of system blur, the second in the histogram/GLCM domain to remove the effect of noise. The performance of the proposed recovery strategy was investigated using a set of texture phantoms and an emulated computed tomography imaging chain with a range of realistic blur and noise levels. The proposed method was able to obtain histogram and GLCM estimates that closely resemble the ground truth. The method performed well across imaging conditions and significantly lowered the variability associated with different imaging protocols. This improvement also translated to better classification accuracy, where recovered radiomic values result in greater separation of radiomic clusters for two different texture phantoms as compared to values derived from the original blurred and noisy images. In summary, the novel radiomics standardization framework demonstrates high potential for mitigating radiomic variability as a result of the imaging system and can potentially be integrated as a preprocessing step towards more robust and reproducible radiomic models.