tbuckley/cabot-search huggingface dataset:
Abstract 4147617: Depression and the Development of Cardiovascular Disease: Insights from All of Us Research Program
Authors: Cameron Blazoski, Zhiqi Yao, Michael Blaha
Journal: Circulation (2024)

Introduction/Background: Depression is recognized as a risk factor for worse outcomes in patients with cardiovascular disease, but there is limited research on whether individuals with depression have an increased incidence of future cardiovascular disease. Research questions/Hypothesis: Do individuals with depression have an increased incidence of cardiovascular disease? Goals/Aims: This study was conducted to evaluate the association between a diagnosis of depression and the risk of developing future cardiovascular events, to determine whether the treatment of depression should be considered as a primary form of cardiovascular disease prevention. Methods/Approach: We conducted a prospective analysis using the “All Of Us” Research Program dataset. Participants who responded to the historical depression status in the “Personal/Family History Survey” and with linked electronic health records data were considered eligible for this study. We used Cox regression models to calculate the incidence of myocardial infarction (MI), stroke, heart failure (HF), and atrial fibrillation (AF) and the hazard ratio (HR) of a diagnosis of depression. Models were adjusted for sex, race, age, and prevalent hypertension, diabetes mellitus, hyperlipidemia, and smoking. The survival analysis of the four outcomes was conducted in parallel. We conducted sensitivity analysis by excluding participants with documentation of prior MI, stroke, HF, and/or AF. Results/Data: 100,030 participants were included in this study, with a mean age of 53.2 (standard deviation of 16.5). 68.4% of participants were female, 10% were Hispanic, 9.6% were Black, and 37.1% had a diagnosis of depression. The median follow up time was 3 years. Compared to participants without depression, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.05–1.41), stroke (aHR 1.68, 95% CI 1.06–2.68), HF (aHR 1.28, 95% CI 1.15–1.43), and AF (aHR 1.14, 95% CI 1.02–1.27). In the sensitivity analysis, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.03–1.44), stroke (aHR 1.68, 95% CI 1.06–2.68), and HF (aHR 1.31, 95% CI 1.15–1.48) but not AF (aHR 1.12, 95% CI 0.99–1.27). Conclusions: This study indicates that patients with a diagnosis of depression were more likely to develop cardiovascular disease, even if they had no known history of cardiovascular disease. Providers should include the treatment of depression as a part of a holistic approach to cardiovascular disease prevention.
Abstract 4136967: Congestive Heart Failure Impedes Effective Fluid Resuscitation in Sepsis
Authors: Zhiyuan Ma, Mahesh Krishnamurthy, Peter Puleo, David Allen, Jamshid Shirani
Journal: Circulation (2024)

Background: Fluid resuscitation is recommended in patients with sepsis. Sepsis, however, may be associated with myocardial dysfunction. Additionally, myocardial dysfunction and insufficient cardiac reserves in patients with congestive heart failure (CHF) may complicate fluid resuscitation in the setting of sepsis. We aimed to determine whether CHF would affect fluid resuscitation in septic patients admitted to intensive care unit. Outcome of patients with and without CHF were compared. Methods: Unmatched and propensity score matched septic patients with or without CHF were examined in a retrospective cohort of critically ill adults from the MIMIC-IV database by multivariable logistic regression. Mortality and length of stay were compared. Generalized additive models were used for assessing association between fluid resuscitation and in-hospital mortality. Results: Of 24,376 critically ill patients with sepsis, 6838 (28.1%) were also diagnosed with CHF. CHF in septic patients was associated with higher in-hospital mortality with an adjusted odds ratios of 1.25 (95% confidence interval (CI)=1.14-1.37; p&lt;0.001) in unmatched analysis. Compared with patients without CHF, those with CHF had higher in-hospital mortality (14.3% vs. 9.8%, p &lt; 0.001) and received less IV fluid in the first 24 hours of ICU stay (median=1936 ml, IQR=808-3654 vs. 3037, IQR=1810-4585 ml, p&lt;0.001). Similar results were obtained in propensity score matched septic patients with or without CHF. We also found that fluid resuscitation had a U-shaped association with in-hospital mortality with a lowest mortality at roughly 60 ml/kg in the first 24 hours of ICU stay in septic patients without CHF. In septic patients with CHF, liberal fluid resuscitation did not reduce mortality, while restrictive fluid resuscitation was associated with an increased mortality rate. Conclusions: CHF was significantly associated with higher in-hospital mortality among septic patients. Adequate fluid resuscitation improved in-hospital mortality in septic patients without but not with CHF.
Abstract 4139195: Tipping Point Analysis Identifies C-terminal src kinase-Collagen 22 Regulation by Inflammation in the Pathogenesis of Early-Stage Pulmonary Arterial Hypertension
Authors: Bradley Wertheim, Ruisheng Wang, Elena Arons, William Oldham, George Alba, Frederick Bowman, Nirmal Sharma, Kathleen Haley, Andriy Samokhin, Robert Padera, Joseph Loscalzo, Brad Maron
Journal: Circulation (2024)

Inflammatory injury to pulmonary artery endothelial cells (PAECs) is a key pathogenetic event that drives fibrotic vascular remodeling in pulmonary arterial hypertension (PAH), a progressive disease that lacks early stage-specific therapeutic targets. In an inflammatory rodent model of PAH, we established early-stage disease based on abnormalities in right ventricular (RV) afterload, pulmonary vascular resistance, and RV cardiomyocyte phenotype that were evident without substantial elevation in pulmonary artery pressure. We performed RNA-Seq on PAEC mRNA isolated ex vivo from control, early-stage, and advanced-stage PAH rats and deployed a ‘tipping point’ methodology to identify key pulmonary endothelial protein-protein interactions (PPIs) that regulate the transition from control to early-stage PAH in silico . Building on prior data on the intersection between glucose and proline signaling in fibrosis, we interrogated our early-stage PAH network for convergent PPIs involving metabolism and fibrosis endotypes. C-terminal src kinase (Csk), a conserved inhibitor of Src, was predicted to regulate PAEC fibrosis and was increased in early-stage PAH. In human PAECs, inflammatory stimuli affected markers of Src activation as well as collagen 22 (Col22A1). We observed that pulmonary arterial Col22A1 expression increased progressively across all PAH stages in vivo and that arterial Col22A1 expression is upregulated in human PAH. Further, although inflammation upregulated total Csk mRNA and protein expression in HPAECs, it decreased phosphorylation of Src at tyrosine 527 (pTyr527Src), a Csk-dependent brake on Src kinase activity. Targeting Src through small molecule inhibition or adenovirus overexpression of Csk to increase pTyr527Src, in turn, attenuated inflammation-induced Col22A1 in vitro . Taken together, these data suggest that acquired inhibition of Csk is a novel molecular mechanism by which inflammation induces pulmonary endothelial dysfunction, Src activation, and fibrosis. In early-stage PAH, disrupted Csk inhibition of Src may induce transcriptional upregulation of Csk as a negative feedback response to Src activation. These data suggest that the Csk-Src-Col22A1 axis is a novel target for advancing early-stage therapeutics in patients with PAH subtypes characterized by inflammatory vascular injury.
Abstract 4136930: Plasminogen Activator Urokinase Receptor (PLAUR) Levels are a Predictor of Adverse Cardiovascular Outcomes in the General Population, Independent of High-Sensitive CRP (hs-CRP)
Authors: Shaimaa Sakr, Ishwar Chuckaree, Veena Agusala, Adithya Yadalam, Chang Liu, Matthew Gold, Shivang Desai, Alexander Razavi, Vardhmaan Jain, Arshed Quyyumi
Journal: Circulation (2024)

Background: The gene Plasminogen Activator Urokinase Receptor (PLAUR) encodes the urokinase plasminogen activator surface receptor (uPAR), which upon cleavage releases Soluble Urokinase Plasminogen Activator Receptor (suPAR). SuPAR has emerged as a novel biomarker of inflammation and immunity and is associated with adverse cardiovascular events, particularly coronary artery disease (CAD), regardless of hs-CRP levels, a well-established inflammatory biomarker. However, whether the PLAUR gene predicts adverse cardiovascular events remains uncertain. Methods: We investigated the relationship between PLAUR levels, measured via Olink Immunoassay, in 40,790 individuals from the UK Biobank, and the occurrence of adverse cardiovascular events such as myocardial infarction (MI), as well as all-cause and cardiovascular mortality. Our analysis involved the use of Cox and Fine and Gray proportional hazards models, adjusting for age, sex, race, HDL, LDL, triglyceride levels, BMI, prevalence of hypertension (HTN), prevalence of type 2 diabetes (T2D), smoking history, and use of blood pressure and cholesterol medications. Main Outcomes: The primary outcome was a composite outcome of cardiovascular mortality and MI and the secondary outcome was all-cause mortality. Results: The mean (SD) age was 58 (8) years, 45% men and 94% white. During a median follow-up of 14 (interquartile range 12.3 – 15) years, 7.9% of the population had an MI, 2.7% suffered cardiovascular death, 9.5% all-cause mortality. After adjusting for aforementioned demographic and clinical factors, as well as medication usage, each standard deviation increase in PLAUR levels was associated with a heightened risk of incident non-fatal MI and cardiovascular (CV) death, with a hazard ratio (HR) of 2.31 (95% CI 2.00-2.45), and all-cause mortality, with an HR of 3.81 (95% CI 3.48-4.18). Even after further adjustment for hs-CRP levels, PLAUR levels remained predictive of non-fatal MI and CV death (HR 2.03, 95% CI 1.83-2.26) and all-cause mortality (HR 3.43, 95% CI 3.12-3.77). Furthermore, in a fully adjusted Cox regression model, a significant interaction between PLAUR levels and sex (p = 0.0003) was observed in predicting the primary outcome. The interaction was found to have a stronger predictive value in females compared to males. Conclusion: PLAUR levels are a strong predictor of adverse cardiovascular outcomes in the general population, independent of traditional risk factors and inflammation.
Abstract 4145899: The Danger of Moderator Band Ectopy: A Case of Premature Ventricular Contraction induced Recurrent Ventricular Fibrillation
Authors: Hussein Krayem, Angkawipa Trongtorsak, Gowtham Grandhi, Gautham Kalahasty
Journal: Circulation (2024)

Introduction: Premature Ventricular Contractions (PVCs) are often a benign arrhythmia. However, those originating from the Purkinje system can result in fatal arrhythmias. One example is PVCs originating from the moderator band (MB) within the right ventricle (RV) of the heart. We present a case of PVCs originating from the MB triggering idiopathic ventricular fibrillation (VF) and electrical storm. Case: A previously healthy 49-year-old woman was admitted following a witnessed VF cardiac arrest. She had recurrent episodes of VF, initially treated with Amiodarone and Procainamide which failed to suppress the recurrent VF. She received 54 external defibrillations before a transvenous pacer (TVP) was placed to override the PVCs at a pacing rate of 110 bpm. Post-resuscitation ECGs revealed frequent PVCs originating from the RV free wall, potentially from the lateral part of MB (Figure 1). Quinidine was added to suppress the PVCs ultimately allowing removal of the TVP. Transthoracic Echocardiogram revealed normal cardiac function and a prominent MB. A cardiac MRI was performed showing no infiltrative disease or any other abnormalities. The patient underwent sympathectomy and defibrillator placement. Despite recurrent cardiac arrest, she had excellent neurologic recovery and was subsequently discharged on Quinidine. Discussion: MB extends from the septal wall to the base of the anterior papillary muscle in the RV, carrying Purkinje fibers(PF) from the right bundle branch as it exits the septum. Purkinje fibers have been shown to initiate arrhythmias by several mechanisms including enhanced automaticity, triggered activity and re-entry. In the genesis of PVCs, triggered activity is the likely mechanism. This can degenerate into VF in a structurally normal heart, hence the term “idiopathic VF”. Familiarity with this entity and ECG features of MB ectopy leads to timely management and may potentially prevent lethal arrhythmias in symptomatic patients with such PVCs. Further studies are required to fully understand the arrhythmogenic mechanisms and the optimal management approach for MB ectopy.
Abstract Su803: Sudden Cardiac Arrest Prediction via Deep Learning Electrocardiogram Analysis
Authors: Luca Neri, Matt Oberdier, Alessandro Orro, Richard Carrick, Marco S. Nobile, Sujai Jaipalli, Mariam Khan, Stefano Diciotti, Claudio Borghi, Henry Halperin
Journal: Circulation (2024)

Background: Sudden cardiac arrest (SCA) is a potentially fatal event that often occurs without prior indications. Hypothesis: It was hypothesized that electrocardiogram (ECG) data could be used in conjunction with Deep Learning (DL) algorithms to predict the occurrence of SCA’s. Aims: To improve SCA outcomes and enable preventative strategies, the ECG data from the Nightingale Open Science - Subtyping Cardiac Arrest dataset were utilized to create a DL model to serve as a screening tool for sudden cardiac arrest. Methods: A publicly-available dataset containing ten seconds of 12-lead ECGs from individuals who had a SCA and persons who did not have a SCA, and information about time from ECG to arrest, and age and sex were utilized for individualized prediction of SCA. Subsets of the initial data were used to train, validate, and test deep convolution neural network models that processed cardiac cycles from single-lead ECG voltage waveforms. Results: The cohort comprised 221 (mean age: 68.5 and #females: 75) patients who experienced SCA and 1046 controls (mean age: 69.7 and #females: 497) who did not have a cardiac arrest. The SCA ECG-DL base model, with ECGs within one day and with age and sex data, had an area under the receiver operating curve (AUROC) of 0.774 during hold-out testing for discrimination of subsequent SCA. With sensitivity set at 95%, the base model specificity of the SCA ECG-DL model was 31%. Gradient-weighted class activation mapping showed that the SCA ECG-DL model relied most heavily on the QRS complex to make predictions. The performance of the SCA ECG-DL model was similar removing age and sex data (AUROC 0.775) and less reliable when predicting SCA within one month (AUROC 0.734) or between one month and one year (AUROC 0.574). Conclusion: DL interpretation of ECG data is a promising means of screening for SCA, and this method explains differences in SCA’s due to age and sex. Model performance improved when ECGs were obtained at shorter intervals to the incident SCA event, and SCA prediction was more dependent upon QRS complex data than other temporal segments of the ECG.
Abstract 4143217: Gender Disparities in Clinical Outcomes Following Transcatheter Aortic Valve Replacement: Insights from the National Inpatient Sample
Authors: Chinenye Odo, Toluwalase Awoyemi, Kayode Ogunniyi, Emmanuel Daniel, Isaac Ogunmola, Ikenna Odoh, Rocio Barriga Guzman, Dania Jaamour, Valentine Nriagu
Journal: Circulation (2024)

Background: Transcatheter aortic valve replacement (TAVR) has revolutionized the management of aortic stenosis, offering a less invasive alternative to surgical valve replacement, particularly for high-risk patients. While TAVR has demonstrated efficacy and safety in various patient populations, there is growing recognition of gender-specific differences in clinical outcomes post-procedure.Understanding gender-related variations in TAVR outcomes is crucial for optimizing patient care and ensuring equitable access to this life-saving therapy. Methods: Using the National Inpatient Sample (2017-2020), we analyzed the characteristics and comorbidities of male and female patients undergoing TAVR. We then assessed the incidence of clinical outcomes between genders, including in-hospital mortality, mechanical ventilation, length of stay, hospital charges, vasopressor requirement, heart block, pacemaker insertion, stroke, acute kidney injury (AKI), vascular complications, and discharge disposition. Multivariate analysis was performed to evaluate mortality risk among congestive heart failure (CHF) patients. Results: Among 234,860 total admissions, females comprised 44.5% (104,365) of the population. Females were slightly older (mean age 79.4 vs. 78.5 years, p &lt; 0.001) and had a lower mean Charlson Comorbidity Index (2.8 vs. 3.1, p &lt; 0.001) compared to males. After adjusting for confounding factors, females had a higher odds ratio for in-hospital mortality (OR 1.48, 95% CI 1.37-1.60, p &lt; 0.001), mechanical ventilation (OR 1.14, 95% CI 1.07-1.20, p &lt; 0.001), stroke (OR 1.55, 95% CI 1.46-1.65, p &lt; 0.001), and vascular complications (OR 1.24, 95% CI 1.19-1.31, p &lt; 0.001). Length of stay (mean difference 0.37 days, 95% CI 0.32-0.42, p &lt; 0.001) and hospital charges (mean difference $3,795, 95% CI 2,488-5,102, p &lt; 0.001) were also significantly higher in females (p &lt; 0.001 for both). Conclusion: The divergent clinical profile and poorer outcomes observed among females undergoing TAVR, characterized by elevated in-hospital mortality, stroke, and vascular complications compared to males, may emphasize the need for gender-specific approaches in TAVR management.
Abstract 4140119: Liver Steatosis and Liver Fibrosis Predict Major Adverse Cardiovascular Events in the CLEAR Outcomes Trial
Authors: Vivian de Jong, Alina Saidi, Manuel Castro Cabezas, Steven Nissen, William Sasiela, Na Li, Leanne Bloedon, Abraham Lincoff, Stephen Nicholls, Diederick Grobbee
Journal: Circulation (2024)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), and progressive stages accompanied by liver fibrosis (LF), have been associated with liver-related and CV complications in middle-aged patients, although data on the latter is limited. Objectives: We evaluated whether liver steatosis (LS) or LF are associated with CV outcomes in a large clinical trial that included patients at high CV risk who were statin intolerant (SI), and if so, whether bempedoic acid (BA) treatment reduces observed increases in CV risk. Methods: CLEAR Outcomes evaluated the efficacy of BA in 13,970 SI patients randomized to BA (180 mg daily) or placebo and followed for a median of 40.6 months. The primary outcome was a 4-component major adverse CV event (MACE4: nonfatal MI, nonfatal stroke, coronary revascularization, or CV death). This post-hoc analysis used the following non-invasive algorithms to estimate the presence of LS and LF at baseline: Framingham Steatosis Index (FSI), Fibrosis-4 Index (FIB-4) and NAFLD Fibrosis Score (NFS). Continuous variables were reported as mean±SD, categorical variables as proportion. Time-to-event data were analysed using a Cox proportional hazards model. Adjusted hazard ratios (aHR) for every 1 unit increase in score, while holding every other variable constant, and corresponding 95% CI were reported. Results: The mean age of included participants was 66±9 years, 48% were female, mean BMI was 30±5 kg/m 2 , and characteristics were balanced over the treatment arms. Baseline FSI was 0.2±1.5, FIB-4 1.3±0.6 and NFS -0.6±1.2. LS was associated with an increased incidence of MACE4 in the whole study population, as indicated by the aHR of 1.09 (1.06-1.12) for 1 unit of FSI increase. LF was also associated with increased risk of MACE4 in the overall population, aHR 1.19 (1.11-1.28) for 1 unit of FIB-4 increase, and aHR 1.14 (1.10-1.19) for 1 unit of NFS increase. For LS, per 1 unit of FSI increase the aHR for MACE4 was lower in the treatment group: aHR of 1.04 (0.99-1.09) for BA vs 1.14 (1.09-1.18) for placebo, interaction p=0.004. For LF, aHR did not differ between groups and no significant interaction with treatment was observed. Conclusion: Both LS and LF are associated with an increased risk of MACE4. Overall, BA was associated with lower rates of MACE4 across categories of LS and LF (data not shown). A lower risk of LS-associated MACE4 was observed in the BA group. These benefits are less clear regarding the MACE4 risk driven by LF.
Abstract 4144552: Difference in Characteristics and Outcomes of Atrial Fibrillation patients based on type of Heart Failure: An NRD Propensity Matched Analysis
Authors: Ajit Brar, Soumiya Ravi, Ayushi Garg, Yashitha Chirumamilla, Mohammed Omer, Nikky Maharjan, Shriya Maini, Luay Alkotob
Journal: Circulation (2024)

Background: Heart Failure(HF) significantly deteriorates outcomes in patients with Atrial Fibrillation. Heart Failure with Preserved Ejection Fraction(HFpEF) and Atrial Fibrillation(AFib) share common disease progression pathways and are gradually increasing in prevalence. Aim: We aim to study the variation in characteristics and outcomes based on type of heart failure in patients with AFib using the National Readmission Database(2016-2020). Methods: NRD database was used to identify patients with Atrial Fibrillation using ICD-10 codes. Patients were stratified into two groups based on the presence of systolic dysfunction and diastolic dysfunction. Patients with combined systolic and diastolic dysfunction were excluded. Information was collected on patient demographics, comorbidities, and outcomes. Propensity score matching was performed to compare outcomes among AFib patients with HFrEF and HFpEF. Results: A total of 6,673,080 patients with AFib and isolated systolic or isolated diastolic dysfunction were included in the analysis. 3,914,695(58.66%) had HFpEF and 2,758,385 (41.34%%) had HFrEF. In the HFpEF group 57.8% were females in comparison with 33.12% females in the HFrEF group. HFpEF group had a higher rate of hypertension (84.9% vs 82%, p&lt;0.001), OSA(19.35 vs 14.9, p&lt;0.001), immunocompromised status (0.06 vs 0.04%, p&lt;0.001), hypothyroidism(23.7% vs 18.47%,P&lt;0.001), Anemia(10.1% vs 7.95%, p&lt;0.001), Pneumonia (13.51%) and Pulmonary disease(37.34% vs 30.98%) as compared to the HFrEF group. In the propensity matched analysis, HFpEF group had lower in-hospital death (5.26% vs 6.59%, p&lt;0.001), acute kidney injury (33.19% vs 38.92%; p&lt;0.001), stroke (0.99% vs 1.71%), cardiogenic shock (1.02% vs 3.29%; p&lt;0.001), Myocardial infarction (3.60% vs 7.65%; p&lt;0.001), sudden cardiac arrest (1.95% vs 2.62%;p&lt;0.001), mechanical circulatory device use(0.16% vs 0.77%;p&lt;0.001) and major adverse cardiovascular event(9.79% vs 16.06%;p&lt;0.001). Discussion: In Afib patients with HFpEF, yearly admissions were higher in comparison to the HFrEF group. Furthermore, we found a higher prevalence of hypertension, obesity, OSA, pulmonary disease, pneumonia, immunocompromised status, hypothyroidism, and anemia in comparison with the HFrEF group. However, mortality rate in HFpEF group and MACE were lower. At present, there are no definite therapies for patients with HFpEF that have displayed a clear mortality benefit highlighting the need for further inquiry.