tbuckley/cabot-search huggingface dataset:
Abstract 4145358: Cardiovascular Outcomes of Glucagon-Like Peptide 1 Receptor Agonists in Patients with or without Diabetes Mellitus, A Meta-Analysis of Randomized Controlled Trials:
Authors: Muhammad Aslam Khan, Asna Aafreen, Hitesh Bhatia, Anza Muhammad, Shraddha Bhattarai, Usman Akbar, Abid Nawaz Khan Adil, Saurabh Sharma
Journal: Circulation (2024)

Objectives: Glucagon-like peptide 1 receptor agonists (GLP-1RA) have emerged as a class of antihyperglycemic agents that also reduce major adverse cardiovascular events (MACE), as proven by multiple recent randomized controlled trials (RCTs). This meta-analysis aims to present up-to-date evidence on the cardiovascular benefits of GLP-1 RA in patients with and without diabetes. Methods: After a detailed search of the PUBMED, COCHRANE, EMBASE and MEDLINE databases from their inception until May 2024, 12 RCTs comparing GLP-1 RA with placebo were included in this study. The outcomes of interest were MACE (composite of death from cardiovascular causes, myocardial infarction, and stroke), cardiovascular (CV) mortality, all-cause mortality, myocardial infarction (MI), heart failure (HF) hospitalizations, and the incidence of atrial flutter and atrial fibrillation. The results were reported as risk ratios (RR) with 95% confidence intervals (CI) using random effects model. Results: This study included 84,362 participants from 12 RCTs, with a median follow-up period of 12-60 months. Patients receiving GLP-1 RA showed significant reductions in MACE (RR: 0.86, 95% CI: 0.82-0.92, p=0.00001), all-cause mortality (RR: 0.87, 95% CI: 0.83-0.91, p=0.00001), CV mortality (RR: 0.86, 95% CI: 0.80-0.92, p=0.0001), MI (RR: 0.88, 95% CI: 0.80-0.96, p=0.006), and HF-related hospitalizations (RR: 0.85, 95% CI: 0.73-0.98, p=0.02) compared to those receiving placebo. No significant difference was observed in the incidence of atrial fibrillation or flutter between the two treatment groups. Conclusion: The use of GLP-1RA in patients, regardless of their diabetes mellitus status, reduces the incidence of MACE, MI, death, and HF-related hospitalization. These results further support the use of this class of medication in eligible patients.
Abstract 4146278: Trends in Obesity-related Cardiovascular Disease Mortality across the United States from 1999-2022: An Analysis of Age, Gender, and Race disparities
Authors: Muhammad Ayyan, Saim Amir, Mark Abdelnour, Afra Zahid, Muhammad Ehsan, Huzaifa Ahmad Cheema, Abia Shahid, Sourbha Dani
Journal: Circulation (2024)

Background: Cardiovascular disease (CVD) is a leading cause of mortality worldwide and is inextricably linked to obesity, which is a modifiable risk factor for the pathology. In this study, we aimed to analyze the trends of obesity-related cardiovascular disease mortality in the United States from a period of 1999-2022 and also explored the incongruities between various epidemiological groups. Methods: Our study involved accessing multiple cause of mortality records obtained from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiological Research (CDC Wonder) database, specifically focusing on obesity-related cardiovascular mortality, from 1999 to 2022. Age-adjusted mortality rates (AAMR) per 100,000 individuals and associated annual percent changes (APC) for the overall study population were calculated. We further analyzed the data by dividing it into epidemiological groups of age, race, gender, and ethnicity. We further stratified the cardiovascular disease mortality into heart failure, hypertension, ischemic heart disease, and cerebrovascular disease. We used Joinpoint Regression Program to analyze trends in AAMR. Results: A total of 33,359 deaths occurred from obesity-related cardiovascular disease in the US from 1999 to 2022. The overall AAMR for obesity-related cardiovascular mortality increased from 1999-2018 with an APC of 5.26, but following this, almost tripled from 2018-2022 with an APC of 14.69. The populations with the highest mortality rates were those in Males, African Americans, non-Hispanics, and the age group of 65-74 years. Among the stratification for the causes of CVD mortality, the highest increase in obesity-related AAMR was observed in hypertensive diseases (APC of 7.56 from 1999-2018, and 15.91 from 2018-2022). Conclusion: Obesity-related CVD mortality experienced a moderate incline in the United States. However, since COVID-19, there has been a significant increase in mortality. Persistent demographic and geographic disparities in mortality underscore the need for further investigation and intervention.
Abstract 4145414: Not just children: A case of Incomplete Kawasaki Disease with shock in a Black adult
Authors: Akhilesh Gonuguntla, Syed Hyder, Vibhu Parcha, Heriberto Santana
Journal: Circulation (2024)

Background: Kawasaki disease (KD) is a systemic vasculitis that is rare and underdiagnosed in adults given its atypical presentation, especially in non-Asian patients. Incomplete KD is characterized by less than 4 of the classic clinical findings of mucocutaneous inflammation and is more common in adults. Kawasaki shock syndrome (KSS) is a rare complication that has features of both cardiogenic and vasoplegic shock. Case: A 48-year-old Black male was admitted for subjective fevers, abdominal pain, cervical adenopathy, and jaundice. Labs include WBC count 13320/cmm with 85% neutrophils, total bilirubin 13.1 mg/dL, direct bilirubin 9.3 mg/dL, AST 64 U/L, ALT 191 U/L, ALP 143 U/L, GGT 201 U/L, and urinalysis with pyuria. Microbiological workup and abdominal imaging were unremarkable. Subsequently, he developed chest pain with hypotension, diffuse ST elevations on ECG, and hsTropI of 638 ng/L. Cardiac catheterization revealed no obstructive CAD but elevated filling pressures with cardiac index of 1.8 L/min/m2, suggestive of myopericarditis with cardiogenic shock. IABP was inserted. TTE revealed EF of 20-25% with global hypokinesis, reduced RV systolic function, mild MR, and mild pericardial effusion. Significant labs include ESR 102 mm/hr, CRP 22 mg/L, ferritin 775 ng/mL, albumin 2.3 gm/dL, hemoglobin 9.3 gm/dL, and platelets 703000/cmm. High-dose aspirin and colchicine were given with significant improvement. IABP was removed 2 days post-placement. Cardiac MRI at 1-week post admission revealed reduced LV systolic function and diffuse pericardial enhancement. Aspirin, colchicine, and GDMT were prescribed at discharge. At 2-week follow-up, symptoms had resolved with normalization of labs. Clinical findings, lab abnormalities, and resolution with high-dose aspirin were suggestive of incomplete KD. The patient was subsequently lost to follow-up. Discussion: Incomplete KD should be considered in an adult patient with myopericarditis and evidence of severe systemic inflammation when all classic findings are not present as current criteria are intended for children. Cervical adenopathy and hepatitis are more common in adults while coronary artery aneurysms are rarer. Early mechanical support in KSS may be beneficial.
Abstract 4145368: Dexmedetomidine for prevention of postoperative delirium in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials
Authors: Lucas Barbosa, Arthur Tavares, Ivo Queiroz, Cynthia Mesquita
Journal: Circulation (2024)

Background: Postoperative delirium is a prevalent complication following cardiac surgery. In recents studies, dexmedetomidine has been proposed as a potential alternative to mitigate this condition. This meta-analysis aimed to evaluate the efficacy of dexmedetomidine for prevention of postoperative delirium after cardiac surgery. Methods: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) analyzing the efficacy of dexmedetomidine compared to placebo in patients undergoing cardiac surgeries. We pooled risk ratios (RR) for binary outcomes with 95% confidence intervals (CI) with a random-effects model. We used R version 4.3.2 for all statistical analyses. Results: Our meta-analysis included 12 RCTs comprising 3016 patients, of whom 1515 (50.2%) were randomized to dexmedetomidine. The mean age ranged from 43 to 74 years among studies. Compared with placebo, dexmedetomidine significantly reduced the incidence of postoperative delirium (RR 0.67; 95% CI: 0.48 to 0.95; p&lt;0.05; Figure A). However, there were no significant differences in hypotension (RR 1.34; 95% CI: 0.75 to 2.42; p=0.33; Figure B), and death (RR 0.83; 95% CI: 0.45 to 1.53; p=0.54; Figure C) between groups. Conclusion: In patients undergoing cardiac surgery dexmedetomidine significantly reduced the incidence of postoperative delirium. Larger RCTs are warranted to validate these results.
Abstract 4145755: Trends and Factors Associated with Lipid-Lowering Therapies and High-Intensity Statin Utilization in 381,046 Patients Hospitalized for Acute Myocardial Infarction: A Nationwide Survey using JROAD-DPC
Authors: Koji Hayakawa, kazuhiro nakao, Sumita Yoko, Koshiro Kanaoka, Kensuke Takagi, Fumiyuki Otsuka, Yu Kataoka, Yasuhide Asaumi, Yoshihiro Miyamoto, Satoshi Yasuda, Teruo Noguchi
Journal: Circulation (2024)

Background: Lipid-lowering therapy plays a crucial role in the secondary prevention of coronary artery disease (CAD), particularly following acute myocardial infarction (AMI). While International Guidelines recommend the early initiation of high-intensity statins post-AMI, there remains limited insight into the patterns of lipid-lowering drug utilization across healthcare systems. Purpose: This study aims to analyze the temporal trends and influencing factors associated with the utilization of lipid-lowering therapy, with a focus on high-intensity statins, among patients hospitalized with AMI. Methods: Using data spanning 2012 to 2020 from the Japanese Registry of All Cardiac and Vascular Diseases (JROAD-DPC), including all procedures and prescriptions during hospitalization, we examined 381,046 AMI cases discharged alive from 1,091 hospitals. We defined lipid-lowering therapies as the use of statins, ezetimibe, or PCSK9 inhibitors, and high-intensity statin use based on the following dosages due to insurance limits in Japan: Atorvastatin 20 mg, Rosuvastatin 10 mg, or Pitavastatin 4 mg per day. We investigated trends in lipid-lowering drug and high-intensity statin use and examined associated factors through subcategory analysis, developing a multivariate mixed logistic regression model with each institute considered a random intercept. Results: Within the cohort (with an average age of 69.2 years and comprising 26.5% females), the proportion of patients receiving any form of lipid-lowering therapies increased from 78.0% to 88.2% between 2012 and 2020. Among these individuals, the percentage of those prescribed any statins rose from 77.8% to 85.8% over the same period. However, the utilization of high-intensity statins remained relatively low, accounting for only 31.3% of cases in 2020 (Figure). In subgroup analyses, the usage of high-intensity statins was notably lower among females (26.8%) compared to males (32.9%) in 2020 (p&lt;0.001). Upon adjusting for multivariate factors, including comorbidities and AMI severity, females exhibited a significantly lower likelihood of receiving high-intensity statin therapy, with an odds ratio of 0.92 (95% CI [0.89, 0.94], p&lt;0.001). Conclusion: The early initiation of high-intensity statins post-AMI remains suboptimal. Disparities in utilization exist for females compared to males. Efforts to promote early adoptation of high-intensity statins are warranted to optimize secondary prevention strategies for AMI patients.
Abstract 4145373: PREVALENCE OF NON-RHEUMATIC MITRAL STENOSIS IN CHRONIC KIDNEY DISEASE: NATIONAL IN-PATIENT SAMPLE ANALYSIS
Authors: Vivek Joseph Varughese, Hella Fiona Mathews
Journal: Circulation (2024)

Background: There have been several studies postulating the association between Mitral valve stenosis (MS) and Chronic Kidney Disease (CKD). Accelerated calcification of the mitral valve is the postulated pathophysioloigcal mechanism. AIM/ RESEARCH QUESTION Aim of the study is to analyze the prevalence of non-rheumatic mitral stenosis (MS) in patients with CKD and End Stage Renal Disease (ESRD) and to assess the association between the conditions. Methods: Using the National In-Patient Sample (NIS) 2019, admissions with documented CKD and ESRD were identified. The prevalence of non rheumatic Mitral stenosis (MS) in the admission cohort was analyzed. Chi-square test was used to analyze the association between the two conditions. RESULTS: We identified 4329 admissions with overlapping diagnoses of non-rheumatic MS and CKD, and 905 admissions with overlapping diagnoses of non-rheumatic MS and ESRD. The prevalence of MS in admissions with the diagnosis of CKD was 43.33% (41.14 – 45.84). Prevalence of MS in admissions with ESRD was 56.07% (49.24 - 64.31). There was significant association between MS and CKD, noted with an Odds ratio of 4.14 (3.78 – 4.52, p=0.00) and also between diagnoses of MS and ESRD: Odds ratio of 3.18 ( 2.73 -3.70, p=0.00). (TABLE 1) Conclusions: Based on our analysis, nearly half of the admissions with documented CKD and ESRD did have diagnosis of Mitral stenosis. The association between the conditions was statistically significant.
Abstract 4146444: Higher total physical activity levels are associated with decreased all-cause mortality in patients with Chagas disease
Authors: Mauro Mediano, Leonardo Ribeiro, Erica Diferenz, Flavia Mazzoli-Rocha, Luiz Fernando Rodrigues Junior, Tatiana Goncalves, Vitor Paravidino, Daniel Kasal, Roberto Saraiva, Alejandro Hasslocher-Moreno, Fernanda Mendes
Journal: Circulation (2024)

Introduction: Higher levels of physical activity (PA) are associated with lower mortality in different populations. However, no previous study evaluated this association among patients with Chagas disease (CD), a neglected tropical disease that affects approximately 7 million people worldwide associated with high mortality rates in its more advanced stages. Aim: This study aimed to assess the association between PA level and all-cause mortality in patients with CD. Methods: This was an observational study including CD patients (confirmed by two serological methods) followed-up at the National Institute of Infectious Diseases Evandro Chagas (INI/Fiocruz). Baseline assessment was conducted from March 2014 to March 2017. PA level was assessed using International Physical Activity Questionnaire short version (IPAQ). Deaths were assessed using patients' medical records and the regional death registry system. The association between PA levels (tertiles and as continuous variable) and mortality was determined by log-rank test and Cox regression models. Adjusted analyses were conducted for potential confounding variables including age, sex, hypertension, diabetes mellitus, dyslipidemia, obesity, clinical form of CD, ejection fraction, and prior use of benznidazole. Results: Of the 361 participants included, 56.2% were women (mean age 60.7±10.7 years). During a median follow-up of 7.2 years (IQR 25-75% 5.4 to 8.0 years), there were 90 deaths (24.9%), of those 39 (32.2%) in the lowest PA tertile, 32 (26.7%) in the intermediate PA tertile, and 19 (15.8%) in the highest PA tertile (p=0.006, Log-Rank test). In adjusted Cox regression analysis, the risk of death was lower in the highest PA tertile compared to those in the lowest PA tertile (HR 0.55; 95% CI 0.31 to 0.96; p&lt;0.001; Table). Furthermore, each increase of 100 MET.minutes/week was associated with a 2% lower risk of all-cause mortality. Similar results were observed after excluding deaths within the first 2 years. Conclusion: A linear dose-response association was observed between increased levels of PA and reduced mortality, demonstrating the importance of encouraging PA in this population.
Abstract 4145352: SGLT2 Inhibitor-Induced Euglycemic Ketoacidosis in a Non-Diabetic Patient with Ischemic Cardiomyopathy
Authors: Sulochana Khadka, Kripa Rajak, Pallavi Matai, Bibek Timilsina, Seema Sharma, Anupam Halder, Evelyn Calderon Martinez, Vikash Jaiswal
Journal: Circulation (2024)

Introduction: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are drugs designed to lower plasma glucose concentration by inhibiting Na + -glucose–coupled transport in the proximal tubule. Clinical trials demonstrate these drugs have favorable effects on cardiovascular outcomes including including slowing the progression of CKD. Although most patients tolerate these drugs, a potential complication is development of ketoacidosis, often with a normal or only a minimally elevated plasma glucose concentration mostly in diabetic patients. We present a case of SGLT-2 inhibitor induced ketoacidosis in a patient without any risk factor. Case Presentation: The patient is a 56-year-old gentleman without significant past medical history who presented to the emergency room with prolonged chest pain for more than 12 hours. He was hemodynamically stable with EKG evidence of acute Q-wave and ST elevation in the anteroseptal leads and high sensitivity troponin of about 78,000. He underwent successful PCI along with placement of two DES at mid LAD and proximal OM. Transthoracic echocardiography post catheterization showed LVEF of 25% with dyskinetic apical and apical inferior segment. Subsequently, GDMT for ischemic cardiomyopathy. Approximately after two days of initiation of GDMT, he was noted to have low bicarbonate of 18 and an AG of 16 following which ABG was drawn that showed metabolic acidosis with a nadir pH of 7.30 and an associated Pco 2 level of 29 mmHg. Despite an abnormal lab, he was clinically asymptomatic with no active complaints. His A1C was found to be 5.4. UA revealed ketones (2+) without glucose. β-Hydroxybutyrate level was elevated to 3.34 mmol/L. On further review of his chart, we saw that he had received two doses of empagliflozin. Diagnosis of euglycemic ketoacidosis, presumably related to SGLT2 inhibitor therapy was made. Endocrinologist recommended the usual management like diabetic ketoacidosis. The patient was then started on dextrose and insulin drip. Following closure of anion gap, drips were discontinued. Later, the patient was discharged home on GDMT without SGLT2 inhibitor. Conclusion: Given the tremendous benefits of SLGT-2 inhibitors in patients with diabetes, heart failure, and CKD, their use is expected to grow significantly. Providers should remain vigilant for potential evidence of the development of euglycemic ketoacidosis even in nondiabetic patients using SGLT-2 inhibitors, so that appropriate intervention is done in a timely manner.
Abstract 4146321: Mitochondrial Fission Protein 1 (Fis1) Regulates Endothelial Function in Resistance Arterioles in Health and Cardiometabolic Disease
Authors: Jingli Wang, Kelsey Nolden, John Egner, Mamatha Kakarla, Megan Harwig, Michelle Roberts, Leggy Arnold, Benjamin Hofeld, Rong Ying, Taylor Wilcox, R. Hill, Michael Widlansky
Journal: Circulation (2024)

Background and Research Question: We have previously shown that mitochondrial fission protein 1 (Fis1) is over-expressed in endothelial cells obtained from humans with diabetes. However, whether Fis1 is mechanistically linked to impaired microvascular endothelial function, either health or cardiometabolic disease, remains unknown. Methods: Fresh resistance arterioles from 73 healthy individuals and 24 individuals with type 2 diabetes (T2DM) by gluteal adipose tissue biopsy or discarded surgical tissue. Endothelium-dependent vasoreactivity was tested with increasing doses of acetylcholine (10 -10 to 10 -5 M) following two different molecular manipulations: (1) intraluminal lentiviral transfection for endothelial-specific Fis 1voverexpression vs. control or (2) intraluminal Fis1 siRNA transfection vs. scrambled control. We developed a small peptide Fis1 inhibitor, pep213, and tested if pep213 improved endothelial function in vessels from T2DM patients and healthy individuals exposed to high glucose (HG, 33mM). The impact of molecular manipulations on mitochondrial superoxide (mtO 2 ●- ) function were performed using mitoNeoD. Result: Fis1 knockdown significantly improved vasodilation to Ach in an endothelial nitric oxide synthase (eNOS)-dependent manner (N=6, P&lt;0.0001) in T2DM vessels and healthy vessels exposed to high glucose (HG=33 mM, N=5, P&lt;0.0001), but had no effect Ach vasodilation in healthy vessels exposed to normal glucose concentrations (NG=90 mg/dL., N=3, P=NS). Fis1 overexpression impaired Ach vasodilation in an eNOS-dependent manner in healthy vessels (N=5, P&lt;0.0001) compared to control transfection. NONOate and papaverine controls for these studies showed effects on smooth muscle reactivity. Intraluminal pep213 (1 µM for 1 hour), reversed impaired eNOS-dependent vasodilation in T2DM vessels (N=5, P&lt;0.001), healthy vessels exposed to HG (N=5, P&lt;0.001), and healthy vessels over-expressing Fis1 (N=5, P&lt;0.05), while a scrambled version of pep213 without ability to bind Fis1 had no effects in any of these scenarios. Pep213 had no effect on vasodilation to NONOate. Pep213 reduced mtO 2 ●- in T2DM and healthy vessels over-expressing Fis1 (N=5, P&lt;0.001). Conclusion: Fis1 mechanistically regulates eNOS-dependent vasoreactivity in human vessels, potentially through reducing mtO 2 ●- levels. Fis1 over-expression may be particularly important in T2DM, and pharmacological inhibition of Fis1 can reverse endothelial dysfunction in T2DM human vessels.
Abstract 4145711: Disparities related to amyloidosis and heart failure: A retrospective analysis of US mortality data
Authors: Hoang Nhat Pham, Ibrahim Ramzi, Abdulla Alabagi, Adam Habib, Danny Aiti, Kenneth Barker, Tom Marco, Numaan Mahmood, Le Duc Thien Ha, Viet Nghi Tran, Phillip Tran, Amitoj Singh
Journal: Circulation (2024)

Background: Cardiac amyloidosis, often unrecognized, presents a significant mortality risk when complicated by heart failure (HF). Disparities in amyloid-related outcomes have been previously identified. Question: What are the mortality trends and disparities associated with amyloidosis and HF in the United States (US) from 1999 to 2020? Methods: Mortality due to amyloid and HF as contributors of death were queried from death certificates within the CDC database during 1999 to 2020. Age-adjusted mortality rates (AAMR) per 100,000 population and 95% confidence intervals were compared by race and ethnicity. Log-linear regression models were utilized to assess temporal variation (annual percentage change [APC]) in mortality. Results: Between 1999 and 2020, there were 9,526 deaths related to HF and amyloidosis, with AAMR rising from 0.09 in 1999 to 0.27 in 2020. While HF-AAMR in general population declined slightly from 1999 to 2020 (average APC -0.4%, p=0.003), HF-related mortality in amyloidosis increased gradually from 1999 to 2013 (APC +1.4%, p=0.048), then accelerated from 2013 to 2020 (APC +13.3%, p&lt;0.001). AAMR was higher in urban (AAMR 0.14) than rural regions (AAMR 0.11), among males (AAMR 0.20) than females (AAMR 0.07). Mortality increased steadily in males from 1999 to 2013 (APC +0.8%, p=0.003) with an accelerating inflection in 2013 to 2020 (APC +13.8%, p&lt;0.001). Mortality in females remained stagnant from 1999 to 2013 (APC -1.0%, p=0.300) followed by an increase from 2013 to 2020 (APC +10.8%, p&lt;0.001). Mortality was highest in Black populations (AAMR 0.33), followed by White (AAMR 0.10), Asian/Pacific (AAMR 0.06), and American Indian populations (AAMR 0.04). Mortality among Black populations remained consistent from 1999 to 2012 (APC +1.1%, p=0.184) followed by an increase from 2012 to 2020 (APC +14.0%, p&lt;0.001). Among White populations, mortality remained stagnant from 1999 to 2013 (APC +0.7%, p=0.302) followed by an increase in mortality starting in 2013 to 2020 (APC +13.5%, p&lt;0.001). Conclusion: Amyloid and HF related mortality increased in the recent 22-year period, primarily starting in 2013. This is likely a result of increased awareness and availability of novel diagnostic testing like Tc-PYP.