tbuckley/cabot-search huggingface dataset:
Abstract 14734: Circulating Sulfhydryl Oxidase and Risk of Cardiovascular Disease
Authors: Juying Qian, Ao Chen, Zhangwei Chen, Junbo Ge
Journal: Circulation (2023)

Introduction: Whether circulating quiescin sulfhydryl oxidase (QSOX) family enzymes level is causally associated with an increased risk of cardiovascular disease remains unestablished. In this study, we applied Mendelian randomization (MR) analysis to investigate the potential causal relationship between circulating QSOX family enzymes and a wide range of cardiovascular disease outcomes in European ancestry. Methods: Independent single nucleotide polymorphisms associated with QSOX1 and QSOX2 at the genome-wide significance level were selected as instrumental variables. Summary-level data for 9 cardiovascular endpoints were obtained from genetic consortia, the UK Biobank study, the FinnGen consortium, HERMES and MEGASTROKE. Results: Higher genetically predicted circulating QSOX2 levels were associated with an increased risk of coronary artery disease. For each standard deviation increase in genetically predicted QSOX2 levels, the odds ratio was 1.05 (95% confidence interval, 1.02, 1.07; p = 0.0001) for coronary artery disease. Significant causal association of genetically determined QSOX2 level with heart failure, ischemic stroke and peripheral artery disease was also found with the inverse-variance weighted MR method. However, no potential causal relationships between circulating QSOX2 and atrial fibrillation, intracerebral hemorrhage, pulmonary embolism, transient ischemic attack and venous thromboembolism were observed. There was no association between genetically predicted QSOX1 and cardiovascular disease. Conclusions: This study reveals suggestive evidence that lowering circulating QSOX2 levels may reduce the risk of coronary artery disease, heart failure, ischemic stroke and peripheral artery disease.
Abstract 18170: Microvascular Complications of Type 2 Diabetes in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction in the DELIVER Trial
Authors: Calum Presslie, Mingming Yang, Akshay S Desai, Brian Claggett, Muthiah Vaduganathan, Rudolf A de Boer, Adrian F Hernandez, Silvio E Inzucchi, Mikhail N Kosiborod, Carolyn S Lam, Felipe Martinez, Sanjiv J Shah, Magnus Petersson, Anna Maria Langkilde, Scott D Solomon, John J McMurray, Pardeep S Jhund
Journal: Circulation (2023)

Introduction: The role of microvascular complications of type 2 diabetes mellitus (T2DM) in heart failure (HF) with mildly reduced or preserved ejection fraction is poorly understood. Aim: To assess outcomes and the response to dapagliflozin in the DELIVER trial by the presence of microvascular complications of T2DM. Methods: DELIVER was a multicentre, double-blind randomised controlled trial in patients with an ejection fraction &gt;40% that compared the efficacy of dapagliflozin to placebo. Data on past medical history of T2DM and microvascular complications (nephropathy, angiopathy, retinopathy, peripheral neuropathy, and autonomic neuropathy) were collected at the initial trial visit. Patients were classed as no T2DM, T2DM only and T2DM and microvascular complications. The primary composite outcome was worsening HF or cardiovascular death. Secondary outcomes were HF events, cardiovascular death, and all-cause mortality. Results: 6263 patients were analysed. 3457 (55.1%) patients did not have T2DM, 1840 (29.4%) had diabetes only and 966 (15.4%) had diabetes with a microvascular complication. The unadjusted and adjusted hazard ratio for the primary and secondary outcomes is shown in the Table for those with T2M and T2DM with MVC compared to no T2DM.The risk of outcomes was highest in those with T2DM and microvascular complications but was not significant after adjustment. There was no difference in the effect of dapagliflozin on each outcome by T2DM status (Table). Conclusions: In HF and an ejection fraction &gt;40%, T2DM with MVC is associated with poorer outcomes. The efficacy of dapagliflozin did not differ by diabetes status or the presence of MVC.
Abstract 14962: Rate of 30-Day Readmission and Economic Burden of Sickle Cell Disease Patients Who Underwent Percutaneous Coronary Intervention and Coronary Artery Bypass Graft Procedure for ST Elevation Myocardial Infarction
Authors: Muayad Alzamara, Oluwasegun Akinti, Kenneth Nworie, Henry Aiwuyo, funlola bada, ADESINA ORIGBEMISOYE, Catherine Illah, Patrick Coello, Emmett Brennan, Alexa Kahn, Michael Fatuyi
Journal: Circulation (2023)

Introduction: Sickle cell disease (SCD) is an inherited disorder in which microvascular occlusion causes complications across multiple organ systems, including the heart. Heart problems are among the most common causes of death in people with SCD. Macrovascular complications can also transpire among SCD. Hypothesis: We sought to determine the 30-Day Readmission rate (30-DRr) of patients with SCD who underwent Percutaneous Coronary Intervention (PCI) and Coronary Artery Bypass Graft (CABG) procedure for ST-Elevation Myocardial Infarction (STEMI) and its impact on mortality and healthcare utilization in the United States. Methods: Using the 2020 National Readmission Database, we conducted a retrospective analysis of patients with SCD after PCI and CABG for STEMI as a principal diagnosis according to ICD-10 codes. Readmission was the first admission to any hospital for any non-trauma diagnosis within 30 days of the index admission. The primary outcome was 30DRr, while secondary outcomes were readmission mortality rate and resource utilization defined by length of stay &amp; patient charge. Results: 77 index hospitalization was observed with a mean age of 57.4 SD± 4.2 years, and 70.6 % were females. The in-hospital mortality rate for index admission was 6.5% (5 of 77), while 30-DRr was 20.8% (15 of 72) (Figure 1). Among this group of readmitted patients (mean age was 61.2 SD± 10.5 years, &amp; 57% were males), In-hospital mortality rate was 13.3% (2 of 15). However, observed 30-DRr among Non-SCD was 9.02% (36,564 of 405,526), which is lower, as well as lower inpatient index and readmission mortality of 4.81% (19,507 of 405,426) and 4.83% (1,764 of 36,564) respectively. Conclusions: Approximately 1 in 5 patients who underwent PCI and CABG procedures for STEMI with underlying SCD had 30-DRr. Readmission mortality was higher compared to index mortality but was not statistically significant. SCD patients are a vulnerable subset who will benefit from outpatient multidisciplinary care.
Abstract 18874: Beyond the Beat: Predicting Frailty in Cardiovascular Patients Using Heart Rate Variability
Authors: Maryia Samuel, Saleena Gul Arif, Jonathan Afilalo
Journal: Circulation (2023)

Introduction: Frailty is the increased vulnerability to health issues due to age-related changes in body composition, mobility, and autonomic control. Heart rate variability (HRV) measures the oscillations between consecutive heartbeats. The LF/HF (low frequency/high frequency) ratio, a parameter of HRV, reflects the complex balance between sympathetic and parasympathetic control and cardiac autonomic regulation. Previous studies have linked the LF/HF ratio with frailty. Our goal was to determine if this association holds true in patients with cardiovascular disease (CVD) and if the LF/HF ratio can be used as a surrogate marker of frailty in these patients. Methods: A cross-sectional study was conducted at McGill University's Jewish General Hospital, involving adult patients at the ambulatory cardiology clinic. Resting HRV was evaluated for 2 minutes and 30 seconds using the Elite HRV CorSense monitor. Patients with electrical pacing, atrial fibrillation, or other arrhythmias during the visit were excluded. Frailty was assessed using the clinical frailty scale (CFS), with a CFS ≥ 5 indicating frailty. Routine comprehensive history and physical examinations were performed. Results: The cohort included 155 patients (66.9 ± 13 years, 68 females). Frailty prevalence was 15% (78.6 ± 10 years, 12 females), with a median LF/HF ratio of 0.37. The non-frail population (64.8 ± 12 years, 56 females) showed a significantly higher LF/HF ratio of 1.01 (p&lt;0.001). This difference was driven by a decrease in LF power in the frail group (78.3 ms 2 ) compared to the non-frail group (231.9 ms 2 , p=0.01). The LF/HF ratio correlated with frailty, decreasing by 0.437 for each unit increase in CFS (p&lt;0.001). An LF/HF ratio of 0.37 best predicted frailty (54% sensitivity, 82% specificity, 0.77 ROC). Adjustment for age, sex, and comorbidities did not alter the association between LF/HF ratio and frailty. Conclusions: The LF/HF ratio exhibits an inverse correlation with frailty, making it a predictive tool for identifying CVD patients who may benefit from further frailty evaluation. Additionally, HRV parameters show potential for monitoring frailty and guiding interventions. However, additional research is needed to assess their practical implementation fully.
Abstract 14943: Trans-Biobank Mendelian Randomization Analyses Identify Distinct and Opposing Pathways in the Association of Lower Plasma Low-Density Lipoprotein-Cholesterol With Risk of Gallstone Disease
Authors: Guo-yi Yang, Amy Mason, Dipender Gill, CM Sching, Stephen Burgess
Journal: Circulation (2023)

Background: Higher plasma LDL-cholesterol increases coronary artery disease risk, while biliary cholesterol promotes gallstone formation. Trial evidence suggests that lowering plasma LDL-cholesterol with bempedoic acid increases gallstone risk. Hypothesis: Different plasma LDL-cholesterol lowering pathways have distinct effects on biliary cholesterol and thereby gallstone disease risk. Methods: We conducted a Mendelian randomization (MR) study using data from the UK Biobank (30,547 gallstone disease cases/336,742 controls), FinnGen (34,461 cases/301,383 controls) and Biobank Japan (9,305 cases/168,253 controls). We firstly performed drug-target MR analyses substantiated by colocalization to investigate the effects of plasma LDL-cholesterol lowering therapies on gallstone risk. We then performed clustered MR analyses followed by pathway analyses to identify distinct pathways in the association of lower plasma LDL-cholesterol with gallstone risk. Results: Genetic mimics of statins were associated with lower gallstone risk, but genetic mimics of PCSK9 inhibitors, mipomersen and bile acid sequestrants were associated with higher gallstone risk. The association for statins was supported by colocalization (posterior probability 98.7%). Clustered MR analyses consistently identified clusters showing opposing associations of lower plasma LDL-cholesterol with gallstone risk. Among variants predicting lower plasma LDL-cholesterol, those associated with lower gallstone risk were mapped to glycosphingolipid biosynthesis pathway, while those associated with higher gallstone risk were mapped to pathways relating to ATP-binding cassette transporters and plasma lipoprotein assembly, remodelling, and clearance. Conclusions: Genetic evidence suggests that different plasma LDL-cholesterol lowering pathways may have opposing effects on gallstone disease risk. Specifically, statins may reduce gallstone disease risk.
Abstract 13603: Inhibition of Exercise-Regulated Long Noncoding RNA SALTe1 Reverses Vascular Aging and Age-Related Cardiac Dysfunction
Authors: Haobo Li, Jiayi Kang, Yirong Zhou, JUSTIN GUERRA, Carolin Lerchenmueller, Wai Lydia Tai, Anthony Rosenzweig
Journal: Circulation (2023)

Rationale: Age is a major risk factor for cardiovascular disease. Recent work suggests vascular aging is an important determinant of longevity and end-organ function, although its role in age-related cardiac dysfunction and how exercise mitigates these phenotypes remain unclear. Objective: To identify exercise-regulated, cardiac long noncoding RNAs (lncRNAs) that modulate vascular aging. Methods and Results: Twenty-month-old mice underwent voluntary wheel running for eight weeks. RNAseq identified a novel set of lncRNAs altered in exercised aged hearts, termed S enescence A ssociated L ncRNA T ranscripts in E xercise (SALTes). SALTe1 was conserved and primarily expressed in endothelial cells (ECs). SALTe1 increased in aged hearts but decreased with exercise. Myocardial perfusion and CD31 positive cells were reduced in 20-month-old vs 10-week-old mice while EC senescence (CD31 and p16 or γH2AX double-positive cells) and cardiac diastolic dysfunction increased (p&lt;0.05 for all). In 20-month-old mice, SALTe1 inhibition using antisense GapmeR or EC-specific knockdown in CAS9-mice reversed multiple hallmarks of vascular aging. Recovery from hindlimb ischemia improved (post-surgery day 28 perfusion ratio, Control: 0.58±0.03 vs GapmeR: 0.73±0.03, p=0.04, n=12/group) and aortic stiffness was reduced to levels seen in young animals. Myocardial perfusion (time-to-peak, Control: 2.585±0.08 vs GapmeR: 2.048±0.11 seconds, p=0.03, n=12/group) improved. Cardiac EC number increased, and EC senescence decreased (p&lt;0.05 for all). Inhibition of SALTe1 reduced E/E’ (-20.16±1.60 vs -15.4±1.10, p=0.04, n=12/group) and increased global longitudinal strain (-15.88±0.84 vs 20.66±1.02, p=0.02, n=12/group). Mechanistic studies in vitro and in vivo revealed that SALTe1 works through regulation of Poly (ADP-Ribose) Polymerase Family Member 9 (PARP9) and RNA-binding protein with multiple splicing (RBPMS). Conclusions: SALTe1 regulates EC senescence through PARP9 and RBPMS. SALTe1 inhibition reverses multiple hallmarks of vascular aging and improves age-related cardiac dysfunction. These findings suggest a primary role for EC senescence in age-related cardiac dysfunction and identify SALTe1 as a potential new therapeutic target.
Abstract 13661: In-Hospital Outcomes, Rates of Development of Complete Heart Block and Rates of Pacemaker Placement in TAVR and SAVR Cases: A 5-year Nationwide Inpatient Sample Analysis
Authors: Spandan Desai, Nicholas Roma, Bruce Ferraro, Kashyap Shah, Michael Durkin
Journal: Circulation (2023)

Introduction: Complete Heart Block (CHB) is a commonly observed post-procedural complication associated with Transcatheter aortic valve replacement (TAVR) and Surgical aortic valve replacement (SAVR). Since 2016, limited data exists on In-hospital outcomes of TAVR and SAVR cases and rates of development of CHB. Methods: National Inpatient Sample 2016-2020 was used to identify and group TAVR and SAVR cases using appropriate ICD codes. Logistic regression was used to compare baseline characteristics and in-hospital outcomes. Results: 590,615 patients underwent aortic valve replacement (AVR) from 2016-2020, of which 49.6% were TAVR and 50.4% were SAVR. The most common diagnosis for AVR in both groups was nonrheumatic trileaflet aortic stenosis (AS) (86.6% in TAVR group and 53.5% in SAVR group, p&lt;0.001). In TAVR cases, development of CHB was more common (8.9%-vs-7.2%, p=0.235) along with increased need for transvenous pacing (16.6%-vs-8.7%, p=0.010) and permanent pacemaker placement (9.4%-vs-6.4%, p&lt;0.001). An upward trend in CHB occurrence and pacemaker placement (PPM) was noted in the TAVR group as shown in Image 1. TAVR group was observed to have higher rates of acute myocardial infarction (MI) (14.5%-vs-12.8%, p=0.074). SAVR group had higher rates of cardiogenic shock (8.10%-vs-2.20, p&lt;0.001) and in-hospital mortality (3.6%-vs-1.30%, p=0.02). Conclusions: Over the past few years, CHB has been more commonly observed with TAVR as compared to SAVR, necessitating increasing use for PPM placement. Despite these trends, in-hospital mortality and complications are lower with TAVR procedure.
Abstract 14846: Rurality and Associated Cardiovascular Events and Mortality in Older Men With Prostate Cancer: Longitudinal SEER Medicare Analysis
Authors: Stephanie Jiang, Vraj Patel, Biplab Datta, Priyanshu Nain, Lakshya Seth, Darryl Nettles, Sarah Malik, Sagar A Patel, Manali Rupji, Kevin Ward, Jeffrey M Switchenko, Justin Moore, Neal L Weintraub, Avirup Guha
Journal: Circulation (2023)

Introduction: The effect of rurality as a social determinant of health in cardiovascular events (CVE) in patients with prostate cancer (PC) is unknown. Methods: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified males ≥ 66 years old with a new primary diagnosis of PC between 2009 and 2017. We also identified those who were undergoing leuprolide androgen deprivation therapy (ADT). These patients were followed to identify a primary outcome of CVE that included heart failure (HF), atrial fibrillation (AF), acute myocardial infarction (AMI), peripheral artery disease (PAD), coronary artery disease (CAD), ischemic stroke (IS) and cardiovascular death. Adjusted Cox proportional hazards modeling was performed to estimate all-cause mortality in PC patients stratified by rurality as defined by Medicare. Adjusted Fine-Gray modeling with appropriate competing risk (mortality or type of mortality) was utilized for other outcomes as presented. We adjusted for demographic factors, social determinants of health, cancer-specific factors, and other cardiovascular risk factors apart from the primary exposure of rurality. Results: This study included 102,225 PC patients. Among these, 4,945 (4.8%) belonged to areas with a population of less than 2,500 or less than 20,000 not next to a metro (rural). The use of ADT was noted in 9,071 (8.9%) of patients. The incidence of new CVE and mortality risk due to rurality is presented in Table 1. Rural area was noted to be a risk factor for all-cause mortality [adjusted hazards ratio (aHR) = 1.114 (95% CI= 1.070-1.161)]. No statistically significant association between CVE and rurality, however, was observed in the data. Conclusions: PC patients have a high burden of pre-existing cardiovascular disease prior to PC diagnosis, and rurality increases all-cause mortality. This is consistent with those who are treated with ADT as well.
Abstract 19083: AI-Enabled ECG Detection of Atrial and Ventricular Septal Defects in Pediatric Patients
Authors: Grace Greason, Donnchadh O'Sullivan, Scott Anjewierden, Zachi Attia, Francisco Lopez-Jimenez, Paul Friedman, Peter A Noseworthy, Jason Anderson, Anthony H Kashou, Benjamin W Eidem, Jonathan N Johnson, Talha Niaz, Malini Madhavan
Journal: Circulation (2023)

Background: Atrial septal defects (ASD) and ventricular septal defects (VSD) are among the most common forms of congenital heart disease (CHD). Early detection and intervention for these defects are crucial to prevent complications. Given advancements in AI technology, the development of AI-enabled ECG models for detecting these defects is of significant interest. Aims: This study aimed to create AI models using pediatric ECG data for the detection of ASD, VSD, and a combined model detecting either ASD or VSD. Methods: We analyzed a dataset of 7,795 pediatric patients from Mayo Clinic who had undergone echocardiography between 2002 and 2022, with corresponding 10-second, 12-lead surface ECGs taken within 14 days of echocardiography. This dataset included 259 patients with ASDs and 139 patients with VSDs (single or multiple). The control group was comprised of 7,397 patients without significant or complex CHD. For cases and controls, we included patients with all forms of electrocardiographic abnormalities and those with valvular lesions who had less than moderate stenosis or regurgitation. The dataset was divided into training, validation, and testing subsets to develop convolutional neural network (CNN) models for ASD, VSD, and either ASD or VSD detection. Results: Our ASD and VSD detection models achieved test AUCs of 0.82 (95% CI 0.76, 0.88) and 0.80 (95% CI 0.70, 0.90), respectively. Meanwhile, a combined model that detected either ASD or VSD demonstrated a test AUC of 0.81 (95% CI, 0.76, 0.86), sensitivity of 0.73, specificity of 0.76, PPV of 0.14, and NPV of 0.98 (Figure 1). Conclusions: AI-enabled ECG models demonstrate promising performance in detecting ASD and VSD in pediatric patients. A combined model that detects either ASD or VSD also shows robust results. Future research should focus on multi-center validation of these models, refining their diagnostic capacities, and investigating their potential for early intervention in CHDs.
Abstract 17496: Exploring the Benefits: Role of Repeat Transesophageal Echocardiography (TEE) in Patients Anticoagulated for Four Weeks
Authors: Nazima Khatun, Ekendilichukwu Nnadi, bisrat nigussie, Suzette Graham-Hill
Journal: Circulation (2023)

Background: A left atrial appendage (LAA) thrombus is a well-known complication of atrial fibrillation (AF). Vitamin K antagonists (VKAs) have been well studied been considered the gold standard for thromboembolic prophylaxis. We present a case of LAA thrombus despite compliance with VKAs. Clinical presentation: A 70-year-old female with atrial fibrillation and diabetes presented with left-sided weakness and left facial droop, CT head showed right middle cerebral artery infarct. Vitals were unremarkable. Electrocardiogram showed AF with a rapid ventricular response. She was on warfarin with the most recent international normalized ratio level of 2.3. Transthoracic echocardiography revealed an ejection fraction of 55%, severe left ventricular hypertrophy, and severely dilated left atrium (LA) with LA diameter of 5.3 cm (&gt;= 4.7 cm in women indicates severe dilatation). Transesophageal echocardiography (TEE) with bubble study demonstrated a large thrombus in the LAA with evidence of patent foramen ovale. The pulse wave Doppler (PWD) of the LAA on TEE also showed an LAA velocity of &lt;20 cm/sec, which indicated that there was the highest probability that the thrombus was forming within LAA. Hypercoagulability work-up for thrombosis while on Coumadin such as anti-B2 glycoprotein, anticardiolipin, and factor V Leiden mutation were negative. The patient was started on enoxaparin with appropriate follow-up upon discharge. Discussion: The prevalence of LAA thrombus in patients with AF receiving a minimum of 3 weeks of anticoagulation, was approximately 3%. The presence of a LAA thrombus is a known contraindication to cardioversion and catheter ablation in patients with AF as it can result in cardioembolic stroke. However, current guidelines for cardioversion do not recommend pre-procedural TEE in patients undergoing cardioversion for AF if they have been on therapeutic oral anticoagulation for at least 3 weeks while TEE use remains variable before catheter ablation.