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.

Prediction of Recurrence of Atrial Fibrillation Post-ablation Based on Atrial Fibrosis Seen on Late Gadolinium Enhancement MRI: A Metaanalysis.

OBJECTIVES: This meta-analysis aims to investigate the recurrence of atrial fibrillation (AF) post-ablation based on the various stages of fibrosis seen in the late gadolinium enhancement magnetic resonance imaging (LGE-MRI). METHODS: Electronic databases were searched using specific terms and identified nine studies that met the inclusion criteria. A total of 1,787 patients underwent LGE-MRI to assess atrial fibrosis before catheter ablation for AF. We performed three analyses: first, we compared stage IV versus stage I (reference group). The second set examined the combined stages III and IV versus stages I and II (reference group). The third set compared stage IV versus combined stages I, II, and III. The metanalysis relied on a random-effects model to pool the odds ratios (OR) and 95% confidence intervals (CI) using the DerSimonian and Laird method. The data was analyzed using StatsDirect software in England. RESULTS: The study showed a higher rate of AF recurrence after ablation in stage IV atrial fibrosis than in stage I (OR, 9.54; 95% CI, 3.81 to 28.89; P<00001). Also, in patients with combined stages III & IV of atrial fibrosis, AF recurrence was significantly higher after ablation than in stages I & II groups (OR, 2.37; 95% CI, 1.61 to 3.50; P<00001). Similarly, compared to combined stages I, II, and III, patients with stage IV have higher odds of recurrence post-ablation (OR, 4.24; 95% CI, 2.39- 7.52, P < 0.001). CONCLUSION: This metanalysis demonstrates the strong association between left atrial fibrosis in LGE-MRI and AF post-ablation recurrence. The finding of this study will further assist clinicians in predicting the recurrence rate of AF based on the amount of fibrosis and tailor therapeutic decisions for further management.

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.

An assessment of race and gender-based biases among readmission predicting tools (HOSPITAL, LACE, and RAHF) in heart failure population.

BACKGROUND: The objective of our study is to retrospectively investigate if the HOSPITAL score, LACE index, and RAHF scale exhibit any bias based on gender and race in heart failure readmissions. METHODS: This is a retrospective cohort study with all adult medical patients discharged with congestive heart failure from 2016 to 2018 from Southern Illinois University School of Medicine Hospitalist service. The receiver operating characteristic (ROC) curve was constructed comparing prediction tools (HOSPITAL score, LACE index, and RAHF scale) performance based on gender and race by measuring the area under the curve (AUC). Absolute Between-ROC Area (ABROCA) values were calculated. All statistical analyses were performed using R version 3.6.2. RESULTS: The performance of the HOSPITAL score in the majority and minority population showed a statistically significant difference between AUCs (0.714 and 0.633, p = 0.029) and an ABROCA of 0.081 indicating superior performance in predicting hospital readmissions in the majority group vs. the minority. The performance of RAHF score in females and males showed statistically significant differences between AUCs (0.567 and 0.527, p = 0.04) and an ABROCA of 0.04 indicating the superior performance of the RAHF score in females compared with males. CONCLUSIONS: Our study demonstrated that the HOSPITAL score and the RAHF scale showed significant differences in predicting 30-day readmissions risk based on race and gender, respectively, in heart failure patients, whereas the LACE index did not show any significant difference.

Social Vulnerability Indices as a Risk Factor for Heart Failure Readmissions.

Objectives: The objective of our study was to use the parameters of social vulnerability index (SVI) to observe their association with the 30-day hospital readmissions in the heart failure population.Methods: Data required for analysis were extracted from the electronic medical record. The geographic SVI data was then merged with the clinical data. Qualitative variables and reported as frequency and quantitative variables and reported as the mean ± standard deviation. Variables from univariate analysis with a P value of ≤ 0.10 were evaluated using multivariate logistic regression with stepwise backward variable selection and receiver operating curve (ROC) analysis.Results: The odds ratio of readmission predicted by HOSPITAL score was 1.137 (P value = 0.004, 95% CI = 1.041-1.241). SVI parameter recording disability showed odds ratio of 1.521 (P value = 0.006, 95% CI = 1.125-2.058) and SVI parameter tracking vehicle ownership showed odds ratio of 15.355 (P value = 0.014, 95% CI = 1.755 - 134.383). The ROCs were generated for three scenarios: (i) HOSPITAL score only which had area under the curve (AUC) of 0.702 (P value = 0.015), (ii) SVI indicators tracking vehicle ownership and disability resulted in the AUC of 0.589 (P value = 0.016), and (iii) all of the above combined increased the AUC increased to 0.718 (P value = 0.015).Conclusions: Two social parameters (limited vehicle access and prevalence of disability) from the SVI showed a strong association with 30-day hospital readmissions.

Comprehensive evaluation of cardiovascular efficacy and safety outcomes of SGLT2 inhibitors in high risk patients of cardiovascular disease: systematic review and meta-analysis.

OBJECTIVES: To demonstrate a magnitude of the cardiovascular benefits, concomitantly analyzing the safety outcomes of sodium-glucose cotransporter 2 inhibitor (SGLT2-I) comprehensively, as a class effect in a larger sample size combined from recent randomized control trials. METHODS: We searched electronic databases using specific terms and evaluated 6 efficacy and 10 safety outcomes. Odds ratios (ORs) and 95% confidence interval (CI) were used to compare two interventions. RESULTS: Five studies (n = 41 267) were included, among which 23 539 received SGLT2-I. The SGLT2-I group favored reduction in major adverse cardiovascular events (OR, 0.78; 95% CI, 0.62-0.98; P = 0.03), cardiovascular death (CVD) or heart failure hospitalization (OR, 0.60; 95% CI, 0.46-0.80; P = 0.0004), rate of hospitalization for heart failure (OR, 0.56; 95% CI, 0.44-0.72; P < 0.00001), CVD (OR, 0.68; 95% CI, 0.50-0.93; P = 0.01), all-cause mortality (OR, 0.67; 95% CI, 0.48-0.93; P = 0.02) and myocardial infarction (OR, 0.79; 95% CI, 0.64-0.99; P = 0.04) when compared to the placebo group. Safety analysis showed higher diabetic ketoacidosis (DKA) rate in SGLT2-I group (OR, 2.33; 95% CI, 1.40-3.90; P = 0.001); in contrast, major hypoglycemic events were significantly lower (OR, 0.79; 95% CI, 0.73-0.87; P < 0.00001). AKI was significantly higher in the placebo group (OR, 0.76; 95% CI, 0.65-0.88; P = 0.0004). There were no statistically significant effects on other outcomes. CONCLUSION: In selected high-risk patients of cardiovascular disease, the SGLT2-I is a potential effective class of drugs for improving cardiovascular outcomes and all-cause mortality without an increased risk of all other major complications except DKA on this meta-analysis.

Man vs. man-made marijuana: A case of drug-induced posterior reversible encephalopathy syndrome (PRES) due to K2, a ynthetic cannabinoid (SCB).

Synthetic Cannabinoids (SCB) are engineered chemical compounds that share a similar chemical structure with the active ingredient of marijuana, delta-9-tetrahydrocanabinol. Although the FDA has not approved the use of SCB without a prescription from a licensed health-care provider, the cost effectiveness and availability of SCB has made it a popular choice among recreational drug users. Manufacture of SCB as a street drug is not regulated. These SCB are highly potent chemicals that cause various severe toxicities. In this case report, we describe an adult who suffered from PRES after consuming K2, a synthetic cannabinoid.

Pulmonary Blastomycosis: A case series and review of unique radiological findings.

Blastomycosis is a systemic fungal infection which primarily involves the lungs but can disseminate to involve extrapulmonary sites. Current testing that exists includes sputum, urine, serum, and pathological tissue analysis. Radiological testing is often non-specific and highly variable. Here we present five cases of pulmonary blastomycosis with challenging radiographic presentations.

Heart Failure Drug Class Effects on 30-Day Readmission Rates in Patients with Heart Failure with Preserved Ejection Fraction: A Retrospective Single Center Study.

Background: The pharmacologic management of heart failure with preserved ejection fraction (HFpEF) involves far fewer options with demonstrated additional benefit. Therefore, we examined the effect of combination of multiple classes of HF medication in the 30-day hospital readmission in patients with HFpEF. Methods: All adult patients discharged with a diagnosis of HFpEF and a left ventricular ejection fraction (LVEF) of ≥ 50% reported during the admission or within the previous six months from our institution were retrospectively studied for a 30-day hospital readmission risk. Individual as well as combination drug therapy at the time of hospital discharge were evaluated using Pearson chi2 test and multivariate logistic regression. Results: The overall 30-day readmission rate in this HFpEF cohort of 445 discharges was 29%. Therapy with loop diuretics (p = 0.011), loop diuretics and angiotensin receptor blocker (p = 0.043) and loop diuretics and beta blockers (p = 0.049) were associated with a lower risk of 30-day hospital readmission. Multivariate logistic regression revealed only loop diuretics to be associated with a lower risk of hospital readmission in patients with HFpEF (OR 0.59; 95% CI, 0.39-0.90; p = 0.013). Conclusions: Our study revealed that loop diuretics at discharge decreases early readmission in patients with HFpEF. Further, our study highlights the implication of a lack of guidelines and treatment challenges in HFpEF patients and emphasizes the importance of a conservative approach in preventing early readmission in patients with HFpEF.

Heart Failure with Preserved Ejection Fraction and 30-Day Readmission.

OBJECTIVE: Several studies identify heart failure (HF) as a potential risk for hospital readmission; however, studies on predictability of heart failure readmission is limited. The objective of this work was to investigate whether a specific type of heart failure (HFpEF or HFrEF) has a higher association to the rate of 30-day hospital readmission and compare their predictability with the two risk scores: HOSPITAL score and LACE index. DESIGN: Retrospective study from single academic center. METHODS: Sample size included adult patients from an academic hospital in a two-year period (2015 - 2017). Exclusion criteria included death, transfer to another hospital, and unadvised leave from hospital. Baseline characteristics, diagnosis-related group, and ICD diagnosis codes were obtained. Variables affecting HOSPITAL score and LACE index and types of heart failure present were also extracted. Qualitative variables were compared using Pearson chi2 or Fisher's exact test (reported as frequency) and quantitative variables using non-parametric Mann-Whitney U test (reported as mean ± standard deviation). Variables from univariate analysis with P values of 0.05 or less were further analyzed using multivariate logistic regression. Odds ratio was used to measure potential risk. RESULTS: The sample size of adult patients in the study period was 1,916. All eligible cohort of patients who were readmitted were analyzed. Cumulative score indicators of HOSPITAL Score, LACE index (including the Charlson Comorbidity Index) predicted 30-day readmissions with P values of <0.001. The P value of HFpEF was found to be significant in the readmitted group (P < 0.001) compared to HFrEF (P = 0.141). Multivariate logistic regression further demonstrated the association of HFpEF with higher risk of readmission with odds ratio of 1.77 (95% CI: 1.25 - 2.50) and P value of 0.001. CONCLUSIONS: Our data from an academic tertiary care center supports HFpEF as an independent risk factor for readmission. Multidisciplinary management of HFpEF may be an important target for interventions to reduce hospital readmissions.

Late Atrial Thrombus Formation After Percutaneous Patent Foramen Ovale Closure.

Late thrombus formation is a rare complication associated with patent foramen ovale (PFO) closure devices. We report the case of an incidental discovery of large thrombi in both atria 9 months after percutaneous PFO occlusion that required cardiac surgery for thrombi removal. (Level of Difficulty: Beginner.).

HOSPITAL Score, LACE Index and LACE+ Index as predictors of 30-day readmission in patients with heart failure.

This study aimed to evaluate the accuracy of the HOSPITAL Score (Haemoglobin level at discharge, Oncology at discharge, Sodium level at discharge, Procedure during hospitalization, Index admission, number of hospital admissions, Length of stay) LACE index (Length of stay, Acute/emergent admission, Charlson comorbidy index score, Emerency department visits in previous 6 months) and LACE+ index in predicting 30-day readmission in patients with diastolic dysfunction. Heart failure remains one of the most common hospital readmissions in adults, leading to significant morbidity and mortality. Different models have been used to predict 30-day hospital readmissions. All adult medical patients discharged from the SIU School of Medicine Hospitalist service from 12 June 2016 to 12 June 2018 with an International Classification of Disease, 10th Revision, Clinical Modification diagnosis of diastolic heart failure were studied retrospectively to evaluate the performance of the HOSPITAL Score, LACE index and LACE+ index readmission risk prediction tools in this patient population. Of the 730 patient discharges with a diagnosis of heart failure with preserved ejection fraction (HFpEF), 692 discharges met the inclusion criteria. Of these discharges, 189 (27%) were readmitted to the same hospital within 30 days. A receiver operating characteristic evaluation showed C-statistic values to be 0.595 (95% CI 0.549 to 0.641) for the HOSPITAL Score, 0.551 (95% CI 0.503 to 0.598) for the LACE index and 0.568 (95% CI 0.522 to 0.615) for the LACE+ index, indicating poor specificity in predicting 30-day readmission. The result of this study demonstrates that the HOSPITAL Score, LACE index and LACE+ index are not effective predictors of 30-day readmission for patients with HFpEF. Further analysis and development of new prediction models are needed to better estimate the 30-day readmission rates in this patient population.

A Rare Case of Isolated and Idiopathic Spontaneous Renal Artery Dissection in a Female Patient on Multiple Medications.

Constituting less than 25% of all renal artery dissections (RAD), isolated spontaneous renal artery dissection (SRAD) is a rare diagnosis that can cause subsequent renal infarction with impairment. The majority of SRAD cases are idiopathic. Management ranges from conservative, medical to endovascular, and surgical repair. We report a case of a young female on multiple medications who presented with SRAD. She presented with acute abdominal pain and was found to have isolated spontaneous renal artery dissection. The etiology of this patient's isolated SRAD could possibly be pinned down to her multiple stimulant medications used after the major known causes were ruled out.

Trimethoprim-sulfamethoxazole Induced Pancytopenia: A Common Occurrence but A Rare Diagnosis.

Trimethoprim-sulfamethoxazole (TMP-SMX) is a bacteriostatic antimicrobial medication used for the treatment of a variety of infections and has many reported skin and hematologic side effects. Due to the easy availability and cost effectiveness, TMP-SMX is one of the medications commonly used for treatment of skin and soft tissue in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. One of the rare hematologic manifestations of TMP-SMX is pancytopenia, which is a reduction in all cell lines. In this case report, we are documenting a case of pancytopenia due to severe drug reaction to TMP-SMX in a 70-year-old female after two weeks of medication use. Upon initial stabilization she underwent a thorough workup and was subsequently diagnosed with severe drug-induced pancytopenia. Detailed history, early diagnosis, prompt discontinuation of the offending medication along with supportive care remain the mainstay of treatment in the management of TMP-SMX induced pancytopenia.