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Introduction: Metabolic pharmacotherapies [Glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter type 2 inhibitors (SGLT2i)] have shown benefit in patients with heart failure and preserved ejection fraction (HFpEF). It remains unclear whether the two classes would have additive effects. Methods: We performed a retrospective study using a de-identified federated database with 89 contributing health care organizations (HCO), including over 126 million patients (TriNetX Research Network, Cambridge, MA; date of data access: May 23, 2024). TriNetX regularly aggregates clinical data directly from participating HCOs, and performs extensive data quality and accuracy assessment. While TriNetX obfuscates institutional information relating to participating HCOs, a typical HCO includes a large academic health center with inpatient, outpatient, and specialty care services. We identified all patients with a diagnosis of Heart failure with preserved ejection fraction (HFpEF, ICD-10: I50.3), and SGLT2i usage. We then categorized this patient population into two cohorts, including patients with concomitant GLP1RA use, and patients without GLP1RA use. For both cohorts, we collected data on patient demographics, and the outcomes of all-cause mortality, and all-cause hospitalization, occurring up to 10-years after the index diagnosis. We evaluated differences in outcome risk using hazards ratios and 95% confidence intervals. Results: Prior to propensity score matching, we identified 114,329 patients, with 7931 patients receiving SGLT2i +GLP1RA vs 106398 receiving SGLT2i-alone. Majority (55.7%) identified as white and 24.4% as African Americans and >90% of the patients had a diagnosis of type 2 diabetes mellitus. After propensity matching, the rate of all-cause hospitalization within the combination group was lower than SGLT2i group (29.6% vs 32.4%, HR 0.76 [0.73- 0.79], P<0.001). All-cause mortality for the combination group was 6.8% versus 10.6% within the SGLT2i-alone group (HR 0.52 [0.47-0.56], P<0.001)). Conclusion: In this propensity-matched cohort, patients with HFpEF receiving GLP1RA and SGLT2i had lower rates of hospitalizations and all-cause mortality compared with those receiving SGLT2i alone. Large randomized controlled trials are warranted to corroborate these findings.

Background: Antithrombotic regimens play a pivotal role in averting complications and ischemic incidents post-percutaneous coronary intervention (PCI) in MI (myocardial infarction) patients. Bivalirudin stands as a viable alternative to unfractionated heparin in this cohort, demonstrating the efficacy and safety profiles. Aim: We aimed to compare the efficacy and safety of bivalirudin versus unfractionated heparin in post-percutaneous coronary intervention (PCI) in MI (myocardial infarction) patients. Research Question : What is the efficacy and safety of Bivalirudin compared to unfractionated heparin in patients with MI undergoing PCI, specifically in terms of major bleeding, cardiovascular mortality, and other major adverse cardiovascular events? Methods: We systematically searched PubMed, including MEDLINE, Embase, Cochrane Library, Google Scholar, ClinicalTrials.gov, and EBSCOhost/CINAHL, from January 1, 2000, through May 29, 2024, for randomized controlled trials (RCTs) that evaluated Bivalirudin versus unfractionated heparin and with a study population of patients with MI undergoing PCI. Data extraction was done using a spreadsheet, and data analysis was done using RevMan 5.4.1 for meta-analysis. The primary efficacy and safety endpoints were major bleeding, major cardiovascular events, cardiovascular mortality, all-cause mortality, myocardial infarction, stent thrombosis, and stroke. Results: Our analysis included 11 RCTs, encompassing a total of 40,919 participants. When compared with unfractionated heparin, bivalirudin was associated with a significant reduction in major bleeding events (RR 0.66 [0.55 to 0.80]; p < 0.0001) and cardiovascular mortality (RR 0.79 [0.67 to 0.92]; p < 0.003). However, there were no significant differences between Bivalirudin and unfractionated heparin in terms of major adverse cardiovascular events (RR 1.02 [0.91 to 1.13]; p = 0.76), all-cause mortality (RR 0.89 [0.78 to 1.01]; p = 0.08), MI (RR 0.99 [0.85 to 1.15]; p = 0.90), stent thrombosis (RR 1.12 [0.53 to 2.40]; p = 0.76), or stroke (RR 0.96 [0.73 to 1.26]; p = 0.75). Conclusion: Our meta-analysis indicates that in patients with MI undergoing PCI, Bivalirudin is associated with lower rates of major bleeding and cardiovascular mortality compared to unfractionated heparin. However, there were no significant differences observed in major adverse cardiovascular events, all-cause mortality, MI, stroke, or stent thrombosis between the two treatment groups.

Background: Persistent atrial fibrillation (AF) presents a significant management challenge, particularly in patients with concurrent heart failure. The effectiveness of catheter ablation compared to medical therapy for these patients remains under debate. Aim: This meta-analysis aims to evaluate the outcomes of catheter ablation versus medical therapy for managing persistent AF. Research Question: How does catheter ablation compare to medical therapy in managing persistent AF considering outcomes like arrhythmia recurrence, hospitalizations, cardiac function, exercise capacity, and mortality? Methods: We performed a meta-analysis of randomized controlled trials (RCTs) comparing catheter ablation with medical therapy in patients with persistent AF. Data sources included PubMed, Embase, Cochrane Library, Clinicaltrial.gov, Google Scholar, and CINAHL/EBSCOHOST, with studies selected based on predefined inclusion criteria. Primary outcomes assessed were recurrence of atrial arrhythmias, hospitalizations, changes in left ventricular ejection fraction (LVEF), changes in 6-minute walk test (6MWT) distance, and all-cause mortality. The data extraction was done using a spreadsheet, and the data analysis was done using RevMan 5.4.1: for meta-analysis Results: A total of 10 RCTs involving 1812 patients were included in the analysis. Compared to medical therapy, catheter ablation significantly reduced the recurrence of atrial arrhythmias (risk ratio [RR] = 0.43, 95% confidence interval [CI]: 0.29-0.63, P < 0.0001). Hospitalization rates due to heart failure were also lower in the ablation group (RR = 0.57, 95% CI: 0.44-0.73, P < 0.001). Improvements in LVEF were observed with a mean difference (MD) of 5.98% (95% CI: 3.81% to 8.15%, P < 0.00001). The performance on the 6MWT was better in the catheter ablation group, with an MD of 28.83 meters (95% CI: 8.61 to 49.05 meters, P = 0.005). Additionally, catheter ablation was associated with a reduction in all-cause mortality (RR = 0.60, 95% CI: 0.45-0.80, P = 0.00006). Conclusion: This meta-analysis demonstrates that catheter ablation is superior to medical therapy in managing persistent atrial fibrillation. Catheter ablation offers significant benefits in reducing atrial arrhythmia recurrence, lowering hospitalization rates, improving cardiac function and exercise capacity, and reducing mortality. These findings support the consideration of catheter ablation as a preferred treatment strategy for patients with persistent AF.

Background We developed a simplified ABC/2‐derived method to estimate total subarachnoid hemorrhage volume (SAHV) on noncontrast computed tomography in patients with aneurysmal SAH and compared the clinical and radiographic outcomes. Methods and Results In this retrospective observational cohort study, we analyzed 277 patients with SAH admitted to our Comprehensive Stroke Center between 2012 and 2022. We derived a mathematical model (model 1) by measuring SAH basal cisternal blood volume using an ABC/2‐derived ellipsoid formula (A=width/thickness, B=length, C=vertical extension) on head noncontrast computed tomography in 5 major SAH cisternal compartments. We compared model 1 against a manual segmentation method (model 2) on noncontrast computed tomography. Data were analyzed using logistic regression analysis, t test, receiver operator characteristic curves, and area under the curve analysis. There was no significant difference in cisternal SAHV analysis between the 2 models ( P =0.14). Mean SAHV by the simplified method was 7.0 mL (95% CI, 5.89–8.09) for good outcome and 16.6 mL (95% CI, 13.49–19.77) for poor outcome. Patients with delayed cerebral ischemia had higher SAHV, with a cutoff value of 10 mL. Conclusions Our simplified ABC/2‐derived method to estimate SAHV is comparable to manual segmentation and can be performed in low‐resource settings. Higher total SAHV was associated with worse outcomes and higher risk of delayed cerebral ischemia. A potential dose–response relationship was observed, with SAHV >10 mL predicting worse outcomes and higher risk of DCI.

Background Intraventricular hemorrhage is a calamitous type of stroke where bleeding into the ventricular system can be defined as: primary, if confined within the ventricles; or secondary, due to intracerebral hemorrhage extending from adjacent parenchyma. Intraventricular blood clot can lead to secondary insult and inflammatory responses that culminates in hydrocephalus as the most common cause of death. Purpose THerein, we report a patient with a high modified Graeb scale and low Glasgow coma scale. She spontaneously recanalized her fourth ventricle, decompressed her reticular activating system with remarkable spontaneous bilateral eye opening, and a consequently experienced a halfway drop in her mGS. Results This is the first reported case of a spontaneous recanalization of 4th ventricle obstruction secondary to IVH without intervention and subsequent dramatic neurological improvement. We believe that the apixaban primarily preserved the liquid state of hemorrhage and her presumed elevated ICP was sufficient to push out the liquified blood in the 4th ventricle into the upper spinal canal , recanalizing the 4th ventricle by continuously creating downward CSF pressure waves. Given the RAS location around the 4th ventricle, we hypothesize spontaneous decompression from the clot lysis triggered the RAS activation with sudden arousal manifested as spontaneous bilateral eyes opening. Hence, we refer to this as the reticular activating system reactivation after ventricular hemorrhage evacuation, or simply the “REVIVE” phenomenon. Conclusion This dramatic improvement from coma to awake state is worthy of recognition for future neurotherapeutic interventions.

Background and objectives: Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic deposition of fat in the liver, in the absence of other secondary causes of fat buildup. The relationship between NAFLD, including alanine aminotransferase (ALT), and glycated haemoglobin (HbA1c), is important for predicting the severity of disease and prognosis. This study aims to investigate the association of HbA1c in type 2 diabetes mellitus (T2DM) patients with NAFLD via measuring the ALT levels. Materials and methods: This retrospective cross-sectional study enroled 130 patients with T2DM and NAFLD. The association between levels of HbA1c and ALT in patients of NAFLD with controlled and uncontrolled T2DM, respectively, was investigated. Stratification was done based on gender and diabetic control, using HbA1c levels as a marker of glycemic control. Serum ALT levels were also compared in both groups. Results: The mean age of the participants was 50.2±5.7 years. The total participants were 130, of which 77 (59.3%) were females and 53 (40.7%) were males. The numbers of patients having uncontrolled T2DM (HbA1c>7%), and controlled T2DM (HbA1c <7%) were 78 (60%) and 52 (40%), respectively. Moreover, 46 (35.3%) females and 32 (24.7%) males had uncontrolled T2DM, and 31 (23.8%) females and 21 (16.2%) males had controlled T2DM. The mean ALT level for uncontrolled and controlled T2DM in female patients was found to be 24.6±3.4 and 13.5±2.4, respectively, (P <0.05). For male patients, it was found to be 54.0±4.9 and 29.1±5.4, respectively (P=0.008). Conclusion: There is a positive association between elevated HbA1c and ALT levels in T2DM patients with NAFLD.

AbstractMorbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra‐rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346–3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias.