tbuckley/cabot-search huggingface dataset:
Abstract 4122290: Association between SGLT2 inhibitors and risk of Dementia and Parkinson’s Disease: A Meta-analysis of 12 Randomized Controlled Trials.
Authors: Vikash Jaiswal, Yusra Mashkoor, Akash Jaiswal, Nishchita Raj, Kripa Rajak, Gregg Fonarow
Journal: Circulation (2024)

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated to reduce the risk of hospitalizations from heart failure and cardiovascular mortality. However, SGLT2i therapy’s potential effects on the risks of dementia and Parkinson’s disease are not well established, with conflicting results based on observational studies. Objective: We sought to evaluate the association between SGLT2i and the risk of dementia and Parkinson’s disease in patients with type 2 diabetes mellitus (T2DM), heart failure, or chronic kidney disease. Methods: We performed a systematic literature search on PubMed, Scopus, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until March 2024 without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model. Results: A total of 12 RCTs with 74, 442 patients (40784 in the SGLT2i group and 33658 in the control group) were included in the analysis. The mean age of patients in SGLT2i and control was 65.3 and 65.2 years respectively. The mean follow-up duration was 2.9 years. Pooled analysis showed that there is no significant association between SGLT2i and the risk of dementia (OR, 1.37 (95%CI: 0.70-2.69), P= 0.36, I2=0%), dementia Alzheimer’s type (OR, 2.62 (95%CI: 0.47-14.49), P= 0.27, I2=0), vascular dementia (OR, O.52 (95%CI: 0.09-2.98), P= 0.46, I2=0%), and Parkinson’s disease (OR, 0.75 (95%CI: 0.25-2.25), P= 0.61, I2=0%) was comparable between SGLT2i and control groups. Conclusion: Our study suggest that there is no significant association between SGLT2i and the risk of dementia, its subtypes, and Parkinson’s disease. Further large-power randomized trials are needed to strengthen the understanding of neuropsychiatric beneficial effects of SGLT2i.
Abstract 4116975: Safety signals with SGLT2 inhibitor use in diabetic males with erythrocytosis, but not in females: Findings from the CANVAS Program and CREDENCE trial
Authors: Yohei Doi, Takayuki Hamano, Yoshitaka Isaka
Journal: Circulation (2024)

Backgrounds: Mediation analyses have shown that an increase in hematocrit (Hct) levels significantly contributes to the cardiorenal benefits of SGLT2 inhibitors (SGLT2i). However, given the link between erythrocytosis and poor prognosis, concerns remain about whether SGLT2i-induced erythropoiesis in patients with erythrocytosis may increase thromboembolic events (TE) including myocardial infarction (MI). Methods: We conducted a pooled analysis utilizing individual participant data from the CANVAS Program and the CREDENCE trial, both aimed to evaluate the efficacy and safety of canagliflozin versus placebo in diabetic patients. The primary outcome was a composite of MI, stroke, or any other TE. Sex-specific Cox analyses were performed to assess effect modifications by baseline Hct levels, treated as categorical (anemia, normal, and erythrocytosis) or continuous variable. Results: Of the participants for whom baseline Hct values were available (98.5% [14,321/14,543]), 35% were female. Canagliflozin significantly increased the percentage of erythrocytosis from baseline to 1 year in males (5.6% to 16.9%) and females (1.9% to 5.2%), unlike placebo. Overall, canagliflozin did not alter the risk of the primary outcome for either male (HR 0.97; 95% CI, 0.86–1.10) or female (HR 0.95; 95% CI, 0.78–1.15). In males, baseline Hct levels modified treatment effect on the primary outcome, whether treated as categorical or continuous variables (Pinteraction &lt;0.05), with benefits in anemic patients and harm in those with erythrocytosis (Figure). Meanwhile, no effect modifications were noted in females. In analyses for each component of the primary outcome, canagliflozin consistently reduced the risk of MI, stroke, and any TE in anemic male patients (HR 0.53, 0.49, and 0.71, respectively). However, mixed results were observed in those with erythrocytosis (HR 1.77, 0.62, and 1.11, respectively), suggesting detrimental effects on the primary outcome in these patients were primarily driven by MI. No heterogeneity by Hct was found for heart failure hospitalization or kidney outcome in both sexes. Conclusion: Canagliflozin may pose a safety concern regarding the risk of TE in diabetic male patients with erythrocytosis.
Abstract 4120434: A Rare Case Of Localized Ventricular Tachycardia Due To Mitral Annular Disjunction And a Subvalvular Aneurysm
Authors: Timothy O'Toole, Michael Binder, Ali Hama Amin
Journal: Circulation (2024)

Introduction: Mitral annular disjunction (MAD) is an abnormality of the mitral valve where a portion of the mitral annulus and valve leaflets insert into the left atrium away from the fibrous annulus. Since its identification in 1981 its diagnosis has increased due to the advancements in cardiac imaging. It’s association with ventricular arrythmia (VA) and sudden cardiac death (SCD) underscores the importance of its identification. We present a case of ventricular tachycardia (VT) that is attributed to MAD with associated sub-mitral valve left ventricular aneurysm (SMA) formation. Case: A 51-year-old African American male with history of posterior papillary muscle premature ventricular contractions (PVC), PVC induced cardiomyopathy, and family history of sudden cardiac death in his mother who presented to the emergency department due to palpitations. Electrocardiogram (ECG) showed sustained monomorphic VT at a rate of 160 bpm. This converted to normal sinus rhythm with intravenous amiodarone and metoprolol. Further work up included cardiac magnetic resonance which identified a 4 x 1.8 x 1.4 cm SMA on the basal inferior and inferolateral walls. There was near transmural late gadolinium enhancement (LGE) of the aneurysm and an associated 7 mm of MAD with posterior mitral valve prolapse (MVP). He underwent left heart catheterization which was normal. ECG showed a superior right axis with associated right bundle branch block which correlated to a basal inferolateral exit and to the location of the SMA. Ultimately the patient underwent implantation of secondary prevention implantable cardioverter-defibrillator and initiation of sotalol. Discussion: The prevalence of MAD is approximately 30% in those with MVP and 8% in the general population. Those patients with MAD and MVP appear to be at higher risk for VA and SCD. The most likely mechanism for this association is the fibrotic changes that occur in the basal inferolateral left ventricle because of mechanical stretch on the papillary muscles by the prolapsing leaflets. The scar and aneurysm that develop can serve as substrate for reentrant VA. Treatment for this involves surgical repair of the mitral valve annulus and correction of the MAD distance which has been shown to improve arrythmia. Conclusion: This case illustrates an important but poorly understood arrhythmogenic entity that will increase in incidence as cardiac imaging advances. Its implications in VA and SCD warrant further research.
Abstract 4121215: Efficacy and Safety of Empagliflozin in Patients with Acute Myocardial Infarction: A meta-analysis of randomized controlled trials
Authors: OGECHUKWU OBI
Journal: Circulation (2024)

Background: Empagliflozin is a sodium glucose co-transporter 2 inhibitor that improves cardiovascular outcomes in patients with type 2 diabetes mellitus, chronic kidney disease and heart failure. Less is known about the efficacy and safety of empagliflozin in patients after acute myocardial infarction. Methods: PubMed, Embase and Cochrane databases were searched for randomized controlled trials (RCTs) that reported the outcomes of interets including all-cause mortality, death from cardiovascular causes, hospitalization due to heart failure etc. Risks ratios (RR) or mean difference (MD) and their 95% confidence intervals (CIs) were computed with the use of random-effect model. Heterogeneity was examined with I 2 statistics. Results: We included 12 RCT articles consisting of 23,178 patients that received empagliflozin after acute myocardial infarction were considered. Empagliflozin was associated with significantly reduced incidence of all-cause mortality (RR 0.72; 95% CI [0.61, 0.85]; P &lt; 0.0001; 5.9% vs 7.4%), death from cardiovascular causes (RR 0.66; 95% CI [0.52, 0.83]; P = 0.0004; 4.0% vs 5.4%), and hospitalization for heart failure (RR 0.66; 95% CI [0.58, 0.76]; P &lt; 0.00001; 3.2% vs 4.7%), acute kidney injury (RR 0.52; 95% CI [0.31, 0.86]; P = 0.01), acute renal failure (RR 0.71; 95% CI [0.55, 0.91]; P = 0.008), adverse events leading to discontinuation (RR 0.89; 95% CI [0.80, 0.99]; P = 0.03), systolic blood pressure (MD -8.59; 95% CI [-13.26, -3.93], P = 0.0003), and thromboembolic events (RR 0.51; 95% CI [0.28, 0.92]; P = 0.03) compared to placebo. However, there was no significant difference between groups with respect to fatal or nonfatal stroke (RR 1.15; 95% CI [0.91, 1.46]; P = 0.23), adverse events leading to lower limb amputation (RR 1.11; 95% CI [0.62, 1.99]; P = 0.73), estimated glomerular filtration rate (MD 0.45; 95% CI [-0.20, 1.10]; P = 0.17), diastolic blood pressure (MD -2.53; 95% CI [-5.40, 0.34]; P = 0.08), body weight (MD -1.04; 95% CI [-4.08, 1.99]; P = 0.50), urinary tract infection (MD 1.04; 95% CI [0.92, 1.17]; P = 0.55), NT- proBNP (MD -115.93; 95% CI [-271.52, 39.66]; P = 0.14), glycated hemoglobin (MD -0.10; 95% CI [-0.41, 0.22]; P = 0.55), and hypoglycemia (RR 0.98; 95% CI [0.89, 1.08]; P = 0.70). Conclusion: Our findings suggest that empagliflozin has superior efficacy and safety compared to placebo for the treatment of patients with acute myocardial infarction with no impact on UTI, eGFR, NT-proBNP, and hypoglycemia.
Abstract 4118086: Doxorubicin Induces a Cytotoxic T-cell Inflammatory Response That Contributes to Cardiac Fibrosis and Systolic Dysfunction
Authors: Abraham Bayer, Maria Zambrano, Sasha Smolgovsky, Zachary Robbe, Abul Ariza, Kuljeet kaur, Machlan Sawden, Anne Avery, Cheryl London, Aarti Asnani, Pilar Alcaide
Journal: Circulation (2024)

Background: Doxorubicin (DR), the most commonly used chemotherapy, results in dose-dependent cardiotoxicity in part by causing oxidative stress, cardiomyocyte death, and cardiac fibrosis. Whether these elicit a cardiac immune response that contributes to DR cardiomyopathy and could be targeted for cardio-protection is unknown. We hypothesized that an aberrant T-cell immune response secondary to cardiac damage contributes to DR cardiomyopathy. Methods: We treated wild type (WT) mice and CD8 + T-cell antigen restricted OTI mice with 5.0 mg/kg of DR or PBS weekly for 4 or 8 weeks and performed targeted antibody depletion of CD8 + and CD4 + T-cells. Primary mouse T-cells and cardiac fibroblasts (CFB) were used for mechanistic studies. Whole blood was analyzed by flow cytometry and proteomics in human and canine lymphoma patients before and after DR initiation. Results: DR treated mice exhibited cardiac CD8 + T-cell infiltration alongside hallmarks of DR cardiomyopathy, including declined ejection fraction (EF) measured by echocardiography, cardiac cell death, and fibrosis determined by TUNEL and picrosirius red stain. Cardiac CD8 + T-cells co-localized with αSMA + CFB and had enhanced expression of the degranulation marker CD107a and IFNγ in DR compared to PBS treated mice. DR hearts also showed increased gene and protein expression of the IFNγ inducible chemokines Cxcl9 and Cxcl10 . DR resulted in increased circulating CD8 + T-cells and the frequency of activated CD8 + cells in the cardiac draining lymph nodes. Targeted antibody depletion of CD8 + but not CD4 + T-cells in the onset of DR treatment improved EF and decreased cardiac fibrosis. OTI mice were protected from DR induced EF decline, cardiac T-cell infiltration, and cardiac fibrosis, indicating an antigen-specific CD8 + T-cell response . Mechanistically, DR induced ICAM-1 expression on CFB and ICAM-1 dependent adhesion of activated CD8 + T-cells, which in turn increased CFB αSMA expression. Contact between CD8 + T-cells and DR-treated CFB caused CD8 + T-cell degranulation and Granzyme B release that contributed to CFB activation. Human and canine cancer patients followed longitudinally had increased circulating CD8 + T-cells after anthracycline treatment, and human plasma levels of CXCL9/CXCL10 correlated with decreased EF post DR. Conclusion: Our data demonstrate a novel role for cytotoxic T-cells in DR cardiomyopathy across 3 species, through CXCL9/10-dependent cardiotropism and CD8 + T-cell dependent fibrosis.
Abstract 4120918: Prevalence Of Prediabetes According To Sleep Apnea Status
Authors: Yoo Jin Um, Sung-il Cho
Journal: Circulation (2024)

Aim: The association between obstructive sleep apnea and prediabetes using STOP-Bang questionnaire is unknown. We aimed to investigate prevalence of prediabetes among people according to sleep apnea status. Methods: This cross-sectional study included 10131 Korean adults without diabetes with information of STOP-Bang score were identified from the dataset of the Korea National Health and Nutrition Examination Survey 2019-2021. Prediabetes was categorized into three subsets: fasting blood glucose only (fasting blood glucose 100-125 mg/dL, HbA1c &lt;5.7%), HbA1c only group (fasting blood glucose &lt;100mg/dL, HbA1c 5.7-6.4%) and both fasting blood glucose and HbA1c group (fasting blood glucose 100-125mg/dL, HbA1c 5.7-6.4%). We used multivariable logistic regression to see the odds ratio and 95% confidence intervals for prediabetes. Results: There were 3828 subjects who reported STOP-Bang score of ≥3, which shows increased risk of OSA. Multivariable-adjusted odds ratio (95% confidence interval) for prediabetes meeting both fasting blood glucose and HbA1c comparing STOP-Bang score of ≥3 with &lt;3 was 1.06 (1.01-1.12). In further evaluation of separate gender groups, statistically significant results were seen in women. The multivariable adjusted result correlated with that of the total population. (odds ratio 1.20, 95% confidence interval 1.10-1.30) This was more prominently seen in postmenopausal women. (odds ratio 1.21, 95% confidence interval 1.11-1.32) Conclusion: In Korean general population, the odds of the risk of obstructive sleep apnea was significant in prediabetes group meeting both fasting blood glucose and HbA1c, especially in postmenopausal women.
Abstract 4115542: Female patients with Andersen-Tawil Syndrome are more prone to develop cardiac arrest.
Authors: Alan Garcia, Ricky Lemus-Zamora, Richard Salama Frisbie, Sai Sri Venkata Yeshwanth Damalapati, Abdul Mueez Alam Kayani, Jorge Gomez Flores
Journal: Circulation (2024)

Background: Andersen-Tawil Syndrome (ATS) is an autosomal dominant disorder characterized by a triad of dysmorphic features, periodic muscular weakness, and ventricular arrhythmias. We presented a meta-analysis of cardiologic-affected ATS patients. Objective: This study sought to compare the characteristic features of ATS according to their gender with a special focus on the cardiologic anomalies. Methods: To enable a meta-analysis, we searched literature reviews of reported cases or cohort studies with ATS between 1994 and 2024. Cases were selected if they presented a cardiologic affection alone or combined with morphologic features, periodic paralysis, or both. A gender comparison was made using the available information. Each variable was calculated using the validated percentage. Numerical variables are expressed as mean or median and SD. Categorical variables are expressed as percentages. Student’s t-test was used for numerical variables. Categorical variables were analyzed using chi-square. The results were expressed as an odds ratio (OR) with a 95% confidence interval (CI). Values of p &lt;0.05 were considered statistically significant. Results: The studied population consisted of 243 cardiologic-affected patients with ATS, 163 females, and 80 Males. Compared to males, females are less likely to present periodic paralysis (p = 0.03, OR = 0.54, 95% CI = 0.30-0.98). Analyzing cardiologic features, females had more syncope episodes than males (73% (n=52) vs. 22.4% (n=15). Only 45% of cases had a prolonged QTc. A longer QTc measure was reported in females (453 ± 52) compared to males (427 ± 55) (p = 0.004). Premature ventricular contractions (PVCs) were the most commonly reported arrhythmia, and bigeminy was the most common type of presentation. Polymorphic PVCs were more prevalent in females than males (p = 0.009, OR = 2.49, 95%CI = 1.24-4.99). Females reported more Ventricular tachycardias (VT) episodes than males, especially Bidirectional (p = 0.01, OR = 2.10, 95%CI = 1.17-3.78). Thirty-five patients had an episode of cardiac arrest, either non-fatal, fatal or in some cases non-fatal, followed by SCD after years. Females were more prone to develop cardiac arrest compared to males (n=29 vs. n=6, respectively; p = 0.03, OR = 2.66, 95%CI = 1.06-6.72). Conclusion: ATS females with cardiologic affection may require a closer follow-up due to the higher risk of developing life-threatening arrhythmias and cardiac arrest than males.
Abstract 4119262: Anti-atherosclerotic Potential of M2 Macrophage-Derived Exosomes by Promoting Cholesterol Efflux of Foam Cell-Like Vascular Smooth Muscle Cells via the PPARγ-LXRα-ABCA1/ ABCG1 Pathway
Authors: shuo wang, yunhui lv, yongchun cui
Journal: Circulation (2024)

Background: Impediment in the excretion of lipid deposits within SMC-derived foam cells (SMC-FCs) is one of the reasons for the continuous expansion of the plaque necrotic core. This study aims to explore the effect and underlying mechanimsm of exosomes secreted by M2 macrophage (M2-exos) on SMC-FCs lipid metabolism and plaque stability. Methods: First, immunofluorescence was used to detect the expression levels of CD45 (a recognized differentially expressed molecule of myeloid and SMC-FCs) and the key proteins of cholesterol efflux pathway, ABCA1 and ABCG1, in human early and late plaques. Exosomes derived from M0 and M2 macrophages were purified by sucrose density gradient centrifugation, and characterized based on specific morphology and surface markers. Western blot, Oil red O staining and cell total cholesterol assay were used to assess the effects of M2-exos on the lipid mechanism of SMC-FCs. RNA-seq was used to detect the miRNA profiles of M2-exos. Quantitative real-time PCR was used to identify candidate miRNAs. The dual-luciferase reporting system was utilized to assess the regulatory effect of candidate miRNA on target gene. Then, the effect of M2-exos on the progression and stability of plaques in ApoE -/- mice was evaluated using Oil red O, H&amp;E, Masson, Movat and immunohistochemistry. Results: Immunofluorescence revealed that compared with early plaques, VSMC-FCs (CD45 - ) were significantly increased in late plaques, and the expression levels of ABCG1 and ABCA1 were marked lower than those in macrophage-derived foam cells (CD45 + ). Purified M2-exos treatment significantly promoted the cholesterol efflux of SMC-FCs in vitro. In high-fat-fed ApoE -/- mice, M2-exos significantly reduced the VSMC-FCs, delayed the progression of plaques, decreased necrotic core area and enhanced plaque stability. MiRNA profiling and comprehensive analysis of signaling pathways showed that M2-exos were rich in miR-7683-3p, which played a key role in regulating SMC-FCs lipid metabolism through PPARγ-LXRα-ABCA1/ABCG1 pathway. Dual-luciferase reporting assay showed that miR-7683-3p can specifically bind to the promoter region of homeobox genes A1(HoxA1), an inhibitor of PPARγ-LXRα-ABCA1/ABCG1 pathway. Conclusion: M2-exos exerted an obvious atherosclerotic protective effect, and the underlying mechanism was closely related to MiR-7683-3p, which targeted the 3’UTR of HoxA1 mRNA and activated the PPARγ-LXRα-ABCA1/ABCG1 mediated cholesterol efflux in SMC-FCs.
Abstract 4120270: Risk Factors for Catastrophic Complications Requiring Emergent Extracorporeal Life Support in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Bryant Fisher, Yisi Wang, Floyd Thoma, Neha Shetty, Pyongsoo Yoon, Johannes Bonatti, David Kaczorowski, Derek Serna-Gallegos, David West, Ibrahim Sultan, Victor Morell, Danny Chu
Journal: Circulation (2024)

Background: Transcatheter Aortic Valve Replacement (TAVR) is often performed in the cardiology catheterization suite. Although rare, instances of annular rupture, cardiac arrest, and coronary occlusion may occur requiring institution of emergent extracorporeal life support (ECLS). This study aims to examine the risk factors for complications requiring ECLS during TAVR procedures to identify patients who may benefit from having procedures performed in hybrid operating rooms. Methods: Data from the Transcatheter Valve Therapy registry for our institution was obtained on patients (n=4908) who underwent TAVR between November 2012 and July 2023. Univariable logistic regression was performed to compare relevant covariates in those requiring intraoperative ECLS (n=23) to the rest of the patient cohort (n=4885). All-cause mortality during the follow-up period was compared to assess the impact of emergent intraoperative ECLS. Results: The patients requiring ECLS experienced significantly higher all-cause mortality (69.6% versus 28.8%, p&lt;0.001) with median follow up of 2 years (Table 1) . Female sex (p=0.013) and smaller annulus size (p=0.007) were significant independent risk factors for complications requiring emergent intraoperative ECLS based on univariable logistic regression (Table 2). Patients requiring ECLS had significantly smaller annulus sizes (21.0-23.2 mm) compared to the uncomplicated cohort (22.0-25.8 mm). Of the patients requiring ECLS, 11 cases (47.8%) were due to annular/ventricular rupture while 4 cases (17.4%) resulted from valve embolization. Of note, valve type (self-expanding versus balloon expandable), annular calcification, and porcelain aorta were not found to be significant risk factors. Conclusions: In this large volume single-center retrospective cohort study, female sex and smaller aortic annular size significantly increased the risk of complications necessitating ECLS support during TAVR procedures. Our study represents the first to identify independent risk factors for catastrophic complications during TAVR procedures. Patients with these high-risk profiles should have their TAVR procedures performed in the hybrid operating room with cardiopulmonary bypass on immediate standby.