tbuckley/cabot-search huggingface dataset:
Abstract 4145081: ACUTE ISCHEMIC STROKE IN YOUNG CANNABIS USERS: A NATIONWIDE ANALYSIS
Authors: Vivek Joseph Varughese, Gowri Anil Peethambar, NIVED JAYARAJ RANJINI, Anvitha Mummadisetty
Journal: Circulation (2024)

Background: The incidence of stroke in young adults is on the rise in the United States. Drug abuse has been proposed as a known modifiable risk factor for stroke in this age group. The association between cannabis use and stroke in young adults is an area that needs further exploration. Research Hypothesis: Cannabis is an independent modifiable risk factor for stroke in young adults with Cannabis Use Disorder(CUD). Aim: To investigate the association between Cannabis Use Disorder(CUD) and Stroke in young adults. Methods: Using the National Inpatient Sample 2019, admissions for stroke in the age group of 18-45 were identified. The cohort was subdivided into admissions with documented CUD. Demographic data of the cohort was analyzed, including the prevalence of comorbid conditions. Using multivariate binomial logistic regression, the association between cannabis use and the occurrence of stroke was studied, after accounting for age, smoking, cocaine abuse, and uncontrolled hypertension(HTN). A two-tailed p-value &lt;0.05 was used to determine statistical significance. Results: Out of the 13,514 stroke admissions identified, 1,027 (7.06%) had documented CUD. Analyzing the population, 63.87% were male, 39.57% were White, 38.5% were Black, and 12.3% were Hispanic. The prevalence of other comorbid conditions in this group included uncontrolled HTN (45.67%), alcohol abuse (15.78%), major depression (13.08%), COPD (11.56%), congestive heart failure (8.95%), and cocaine abuse (5.98%). [Table 1] The crude odds ratio (OR) for stroke among admissions with CUD was 2.998 (95% CI: 2.587-3.473, p=0.000). Significant association with stroke was also found between documented cocaine abuse (OR: 1.604, 95%CI: 1.195-2.152), smoking (OR: 2.214, 95%CI: 1.374-3.569), and uncontrolled HTN (OR: 2.114, 95%CI: 1.959-2.281,). Using binomial logistic regression analysis, after adjusting for age, smoking, cocaine abuse, and uncontrolled hypertension, the association between stroke and cannabis use disorder remained significant: OR of 2.956 (95%CI: 2.541-3.440). [Table 2] Further analyzing 543,445 admissions of individuals aged 18-45 with documented CUD, we identified the following as significant risk factors for the occurrence of stroke: Black race (OR: 1.556, 95%CI: 1.16-2.08), uncontrolled hypertension (OR: 5.222, 95%CI: 3.92-6.94), congestive heart failure (OR: 2.763, 95%CI: 1.67-4.55), and a history of myocardial infarction (OR: 2.346, 95%CI: 1.15-4.76). [Table 3]
Abstract 4145148: The Hypertrophic Cardiomyopathy Associated Junctophilin-2 E169K Variant Disrupts Mitofusin-2 Binding and Elicits a Pathological Cellular Response to Metabolic Stress
Authors: Minwoo Kim, Lynn Hartweck, Ryan Moon, Rashmi Raveendran, Kurt Prins
Journal: Circulation (2024)

Introduction: Junctophilin-2 (JPH2) plays essential roles in multiple cardiac processes including calcium handling, t-tubule structure, and gene regulation. We recently showed JPH2 also has a mitochondrial role as it binds the mitochondrial protein mitofusin-2 (MFN2) and modulates mitochondrial metabolic function. However, the impacts of JPH2 disease-causing variants on MFN2 binding and subsequent cellular responses to metabolic stressors are unknown. Methods: Disease-associated variants in the MFN2 binding domain of JPH2 were engineered and recombinantly expressed in E. coli cells. Purified proteins were then subjected to pulldown experiments to assess MFN2 protein binding. Alphafold3 modeled how MFN2 and JPH2 and JPH2 E169K mutants interacted in the presence or absence of fatty acids. Wildtype JPH2 or JPH2 E169K expression was directed by a doxycycline inducible promoter after being cloned into the AAVS1 locus in JPH2 knockout iPSC-cardiomyocytes. In vitro metabolic stress was induced by incubating iPSC-CM with 150 μM oleate, 150 μM palmitate, and 500 μM carnitine overnight. Super resolution confocal microscopy visualized mitochondria integrity, nuclei shape and size, and lipid droplet accumulation and morphology. Results: In pulldown experiments, the JPH2 E169K mutation disrupted MFN2 binding. Alphafold3-based modeling showed JPH2 E169K disrupted the interaction between the two proteins when modeled with or without lipids (A-D). Control, wild type JPH2, and JPH2 E169K iPSC-CM displayed divergent responses to in vitro metabolic stress. JPH2 E169K cells exhibited pathological mitochondrial network changes characterized by a lower mitochondrial footprint and less network branches (E-G). In addition, the JPH2 E169K iPSC-CM accumulated significantly more lipid droplets in the cytoplasm and the nucleus, and the JPH2 E169K lipid droplets were significantly larger than the other cell types (H-K). Finally, the accumulation of lipid droplets impacted nuclear morphology as the JPH2 E169K cells had nuclear hypertrophy and nuclei were more ellipse-shaped (L-N). Conclusion: The JPH2 E169K variant disrupts MFN2 binding, which results in heightened metabolic stress characterized by lipid droplet accumulation and mitochondrial and nuclear morphological changes. These results implicate a new pathophysiological mechanism for how the JPH2 E169K mutation causes cardiac dysfunction.
Abstract 4145048: PAROXYSMAL ATRIAL FIBRILLATION PATIENTS ON ANTICOAGULATION PRESENTING WITH EMBOLIC STROKE: A NATIONWIDE ANALYSIS
Authors: Vivek Joseph Varughese, Gowri Anil Peethambar, NIVED JAYARAJ RANJINI, Anvitha Mummadisetty, Souvik Sen
Journal: Circulation (2024)

Introduction/ Background: Paroxysmal Atrial Fibrillation is a clinical condition that increases the risk for embolic stroke. Current guidelines suggest anticoagulating patients with atrial fibrillation when the chadvasc score is &gt; 2 to decrease the risk of embolic stroke. Aim/ Research Questions: Analyze comorbid conditions that holds significant associations with occurence of embolic stroke in paroxsymal atrial fibrillation admissions while being on long term anticoagulation. Methods/Approach: We used National inpatient Sample (2019) to identify admissions for embolic pattern stroke, with documented history of Paroxysmal Atrial Fibrillation (p AFib) on chronic anticoagulation (AC) (Age group &gt; 18 years).Prevalence of comorbid conditions in the cohort was analyzed. Associations of the comorbid conditions with occurrence of embolic stroke in the admission cohort was analyzed using multivariate linear regression. A two tailed p value &lt; 0.05 was used to define significance in all the calculations. Results/Data: (descriptive and inferential statistics) Of 4780 admissions for embolic stroke with comorbid Pafib on chronic AC were identified. Mean age of the admission cohort was 76.94. Of the admissions, 38.192% had congestive heart failure, 25.83% had chronic kidney disease, 41.94% had uncontrolled hypertension, 54.18% had diagnosis of unspecified hyperlipidemia, 0.523% had Hypertrophic obstructive cardiomyopathy, 0.73% had rheumatic/non rheumatic mitral stenosis listed as their comorbidities. Statistically significant association was seen between uncontrolled hypertension and occurence of embolic stroke OR: 1.997. 95%: 1.756- 2.27. Documented diagnosis of unspecified hyperlipidemia had statistically significant association with admissions for embolic stroke in the patient cohort: OR: 1.642, 95% CI: 1.214 – 1.845). Presence of coexisting HOCM and Mitral stenosis had positive ODDs but did not reach statistical significance {HOCM: OR :1.50, 95% :0.062 - 3.63 and Mitral stenosis: OR: 1.59, 95%: 0.075- 3.36). (Table 1) There was no statistically significant association between CHF, CKD, smoking or with presence of prosthetic valve with embolic stroke. (HOCM: hypertrophic obstructive cardiomyopathy) (OR: Odds Ratio) Conclusion(s): Based on our analysis, presence of uncontrolled hypertension and hyperlipidemia had significant association with the occurrence of embolic stroke in paroxysmal atrial fibrillation population who were on long term anticoagulation.
Abstract 4144910: AI-Enhanced Recognition of Occlusion in Acute Coronary Syndrome (AERO-ACS): A Retrospective Review
Authors: James Choi, Vincent Torelli, Sara Diaz, Esha Vaish, Luka Katic, Alex Nagourney, Zara Khan, Alex Silverman, Serdar Farhan
Journal: Circulation (2024)

Introduction: Traditional ST-elevation criteria do not exhibit high sensitivity for acute occlusion detection, with many total occlusions presenting as NSTEMI, often resulting in worse outcomes. AI-based EKG interpretation may improve the identification of occlusion myocardial infarction (OMI). This study evaluates a novel AI-EKG device's accuracy and clinical outcomes for detecting OMI in suspected ACS patients. Methods: Adult patients who underwent coronary angiogram (CAG) at Mount Sinai Morningside Hospital for unstable angina, NSTEMI, or STEMI between January 1 and December 31, 2022, were included. The AI model (PMCardio) analyzed all pre-CAG ECGs. Inclusion criteria: suspected ACS at the emergency department, no outside hospital transfers, and available peak troponin levels. OMI was defined as a culprit vessel with TIMI 0-2 flow or TIMI 3 flow and peak cTnI &gt; 10.0 ng/mL. Primary outcome: AI EKG model's sensitivity and specificity for predicting OMI on CAG. Secondary outcomes: F1 score, predictive values, AI OMI prediction of inpatient mortality, reduced ejection fraction at 1 year, unplanned readmissions, and STEMI criteria performance. Results: Of 257 patients, 222 met the inclusion criteria: 72 STEMI (32%), 145 NSTEMI (65%), and 5 unstable angina (3%). Confirmed angiographic OMI: 60 (83%) STEMI and 51 (35%) NSTEMI patients. AI model sensitivity was 81.08%, specificity 87.39%, AUROC 0.8423, F1 score 0.8372, PPV 86.54%, NPV 82.20%. Odds ratio of 12.44 (1.56 - 98.98) for AI-detected OMI patients, unplanned readmissions (OR 1.15 [0.53 - 2.51]), and reduced ejection fraction at 1 year (OR 0.24 [0.26 -2 .16]). Traditional STEMI criteria sensitivity for OMI was 54.05%, and specificity 89.29%. The AI model was 100% sensitive for STEMI-OMI and correctly reclassified 8 out of 12 false positive STEMI patients as NOMI. Conclusion: The AI model nearly doubles the sensitivity of traditional STEMI criteria for OMI, enabling more accurate and earlier detection. Further studies are needed to determine if earlier OMI detection with AI improves clinical outcomes. The AI's high specificity in detecting STEMI-OMI may also reduce false positive catheterization lab activations while ensuring no true positive STEMI OMI cases are missed.
Abstract 4144938: Echocardiographic Insights into Subclinical Cardiac Abnormalities in Genotype-Positive Phenotype-Negative Transthyretin (ATTR) Cardiomyopathy
Authors: Gracia Fahed, shadi bagherzadeh, Isaiah Jimenez, Marina Adrianzen Fonseca, Lindsey Chun, Xiu Tang, Michael Salerno, Ronald Witteles, Kevin Alexander, Francois Haddad
Journal: Circulation (2024)

Background: Hereditary transthyretin amyloidosis (ATTR) is often missed due to variable presentations, ranging from primarily neurologic to solely cardiac. Nearly 50% of ATTR mutation carriers develop cardiomyopathy; thus, understanding their subclinical echocardiographic abnormalities could inform early disease presentation. Objective: Define the echocardiographic profiles of ATTR genotype-positive, cardiac phenotype-negative (Gen+/Ph-) individuals compared to matched controls and those with confirmed cardiac disease (Gen+/Ph+). Methods: ATTR Gen+/Ph- individuals were identified based on positive genetic test and no signs of cardiac infiltration by routine echo or PYP scan. Baseline echocardiograms were analyzed and compared to age-, sex- and comorbidity-matched controls, and to Gen+/Ph+ patients with ejection fraction &gt;50%. Structural indices, diastolic parameters and 2D strain analyses of the left ventricle (LV), left atrium (LA), right ventricle (RV) and right atrium (RA) were measured and compared for differences in rank (Mann-Whitney U test) and in effect size (Cliff’s δ). Results: In the ATTR Gen+/Ph- group (n=39), mean age was 52±12 years, 69% were female. Mutations were V122I (23%), V30M (30%) and T60A (26%). The distribution of functional echocardiographic indices differed significantly from controls (n=78) (Table 1), with the largest effect size observed for RA reservoir strain, RV free wall longitudinal strain and LA reservoir strain (Figure 1). The proportion of ATTR Gen+/Ph- patients meeting the guidelines abnormal thresholds was different from controls for E/e’&gt;14 (1.3% vs 10.3%), p=0.04),RV strain&gt;-20% (1.3% vs 12.8%, p=0.02) and RA reservoir strain&gt;-25% (1.3% vs 17.9%, p&lt;0.01). Compared to a Gen+/Ph+ group (n=43), the distribution of all measured parameters differed significantly from the Gen+/Ph- group. Conclusion: ATTR genetic carriers seem to be most different from controls in certain functional, rather than structural, echocardiographic indices. Longitudinal studies are needed to guide screening and early management in this population.
Abstract 4145068: Machine learning analysis of serum proteome in the diagnosis of COVID-19 myocarditis
Authors: Kyle Gordon, Cade William Gordon, Ana Roman, Samuel Watson, Matthew Tong, Daniel Addison, Daniel Jones, Eugene Oltz, Gerard Lozanski, Shan-Lu Liu, Curt Daniels, Saurabh Rajpal, Francesca Madiai, Richard Gumina
Journal: Circulation (2024)

Background: The COVID-19 global pandemic was the third leading cause of mortality in the US in 2020 and is associated with numerous complications, including myocarditis. Diagnosis of COVID-19 myocarditis can involve costly and invasive procedures. In addition, asymptomatic myocarditis could place people at risk for arrhythmias and sudden cardiac death. Objective: To use machine learning (ML) of serum proteomics to distinguish asymptomatic COVID-19 positive volunteers with and without myocarditis. Approach and Results: In 2020, for a cohort of 20 previously healthy 18–23-year-old individuals diagnosed with COVID-19 two weeks after the diagnosis, CMR was performed to assess for evidence of cardiac inflammation and serum samples were obtained the same day (10 were diagnosed as myocarditis positive and 10 negative) We performed proteomic analysis using the SomaScan proteomics assay from SomaLogic. The data were passed through an initial feature selection process of 1000 rounds of bootstrapped multivariate logistic regression using L1-regularization to introduce sparser feature utilization. The top 25 features (largest absolute log-odds) were utilized for a final logistic regression analysis. The feature selection step was optimized to have an average receiver operating characteristic area under the curve (ROCAUC) of 83.29% over 1000 iterations, but the final model utilizing only 25 proteins achieved an average ROCAUC of 99.58%. This method produced 22 proteins with significant odds-ratios for COVID-19 myocarditis (OR 95%CI excluding 1), of particular interest are those involved in inflammatory control and injury response mechanisms. Increases in the heat shock protein DNAJB11 (1.19 [1.10, 1.27]) and calponin-2 (1.17 [1.10, 1.25]), as well as decreases IL1RN (0.88 [0.83, 0.93]) were associated in increased likelihood of CMR diagnosed myocarditis (Fig 1A). Furthermore, a UMAP projection of the data using the 22 significant features yielded a clear visual distinction between those with and without COVID-19 myocarditis via CMR (Fig 1B). Conclusion: Utilizing ML on serum proteomic screenings of asymptomatic young COVID-19 patients, we can differentiate between those with CMR myocarditis positive and negative patients.
Abstract 4144970: Prognosis of Percutaneous Coronary Intervention Versus Optimal Medical Therapy in the Treatment of Chronic Total Coronary Occlusion: A Systematic Review and Meta-Analysis
Authors: Napat Suriyathumrongkul, Nisha Wanichwecharungruang, Natnicha leelaviwat, Phuuwadith Wattanachayakul, Narathorn Kulthamrongsri, Thitiphan Srikulmontri, Wasawat Vutthikraivit
Journal: Circulation (2024)

Introduction: Chronic total coronary occlusion (CTO) management remains a challenge. Several studies have reported the benefits of percutaneous coronary intervention (PCI) in CTO. However, the outcomes of PCI vs optimal medical therapy (OMT) are still controversial. We conducted an extensive review and meta-analysis to compare the clinical outcomes between PCI and OMT in CTO. Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2024. Included studies were published cohort (prospective or retrospective) with propensity score matching analysis and randomized trials that reported all-cause death, cardiac death, and myocardial infarction (MI) with PCI and OMT in CTO patients. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate odd ratios and 95% confidence intervals. Results: Sixteen studies, 6 randomized controlled trials (RCTs) and 11 observational studies with propensity score with matching (PSMs), were included in this meta-analysis involving 8,316 CTO patients (4,332 underwent PCI and 4,084 received OMT). In the overall analysis, all-cause death, cardiac death, and MI were significantly reduced in PCI compared to OMT group, respectively ([OR] 0.65, 95% CI 0.55-0.76, I 2 =0.0%, p&lt;0.001, [OR] 0.60, 95% CI 0.49-0.74, I 2 =0.0%, p&lt;0.001, and [OR] 0.72, 95% CI 0.52-0.99, I 2 =19.0%, p=0.041). Conclusions: Our study is the most updated meta-analysis to assess the impact of PCI compared to OMT in patients with CTO, analyzing the data being derived from PSMs and RCTs, that demonstrated significant impact of PCI on all-cause death, cardiac mortality, and MI.
Abstract 4144991: Exploring Optimal Cardiac Electronic Implantable Devices Programming: Reducing Non-Actionable Alerts and Assessing Clinical Outcomes
Authors: Mohamed Mostafa, George Bodziock, Amber Seiler, John Dillon, Lindsey Cotten, James Allred, Prashant Bhave
Journal: Circulation (2024)

Background: Remote monitoring for cardiac electronic implantable devices (CIEDs) has become standard of care, resulting in an abundance of remote transmission data. While this data is valuable, the number of clinically irrelevant non-actionable alerts (NAA) can lead to alert fatigue and reduce device clinic efficiency. Objective: We aimed to propose clinically reasonable alert parameters to reduce the number of NAA and explore its impact on clinical outcomes. Methods: We included 412 participants with CIEDs indicated for atrial fibrillation (AF) or non-sustained ventricular tachycardia (NSVT) from a single academic medical center. Reprogramming changes set as no alerts for AF episodes &lt; 5.5 hours, persistent AF episodes &gt; 1 month when a prior alert has already been issued, AF episodes &lt; 24 hours in patients with paroxysmal AF on anticoagulation or with left atrial appendage occlusion, NSVT in patients with defibrillators. The number of NAAs were tracked 90 days before and after reprogramming. Incident ischemic stroke and sudden cardiac death (SCD) was ascertained over a median follow-up of 20.9 months. Linear regression was used to compare differences in alarms between pre- and post-periods, and multivariable linear regression was applied to identify factors associated with alerts. Results: Among participants, indication for reprogramming included 69% (n=285) patients with AF and 30.7% (n=127) with NSVT. Compared to pre-programming, the number of NAAs was significantly lower post reprogramming implementation (median [IQR]: 3 [6] vs. 1 [2], P &lt; 0.001) respectively. During follow up, the incidence of primary outcomes was 3.6% ( n :15) for ischemic stroke and 0.7% ( n= 3) for SCD. ( Table ) Conclusion: Our findings demonstrate that implementing guidelines-derived alert parameters in patients with CIEDs significantly reduces the number of clinically irrelevant NAA. This reduction in NAA appears to be safe, with incidence of adverse clinical outcomes comparable to the general population of patients with CIED. This approach has the potential toreduce clinician alert fatigue and safely improve efficiency of device clinics.
Abstract 4144992: Ambient Air Pollution Heightens Prevalence and Adverse Impacts of Clonal Hematopoiesis of Indeterminate Potential
Authors: Shady Abohashem, Wesam Aldosoky, Md Mesbah Uddin, Giovanni Civieri, HUI CHONG LAU, Krystel AbiKaram, Alula Assefa, Sanjay Rajagopalan, Michael Osborne, Pradeep Natarajan, Ahmed Tawakol
Journal: Circulation (2024)

Background: Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the expansion of somatic leukemogenic variations in hematopoietic stem cells, has been linked to atherosclerotic cardiovascular disease. While particulate matter with aerodynamic diameter ≤2.5 micrometers (PM 2.5 ) is known to elevate major adverse cardiovascular event (MACE) risk, potentially through enhanced leukopoietic activity, the specific connection between PM 2.5 and CHIP and their combined role in MACE risk, remains unclear. Hypothesis: We hypothesized that high levels of PM 2.5 exposure are associated with increased CHIP prevalence, which in turn mediates the relationship between PM 2.5 exposure and MACE risk. Methods: We analyzed data of 7015 participants from the Mass General Brigham Biobank, who had undergone genotyping and had their PM 2.5 exposure quantified (for the year prior to consent) based on residential addresses. CHIP detection utilized whole-exome sequencing of blood DNA. MACE diagnosis and risk factors were assessed using ICD codes and health surveys. Multivariable logistic regressions and mediation analysis were employed. Results: Of the participants (mean age of 64 (SD 0.2) years and 47.8% male), 972 exhibited CHIP. High PM 2.5 exposure was associated with an increased risk of CHIP (standardized odds ratio [OR] 1.140 [95% CI: 1.031, 1.262], p=0.011; Fig 1A ) and a higher number of CHIP mutations (OR:1.403 [95% CI: 1.123, 1.753], p=0.003; Fig 1B ) after adjusting for covariables related to CHIP*. Further, CHIP mediated the relationship between PM 2.5 exposure and MACE risk (p&lt;0.05). Notably, MACE risk was greatest among individuals with CHIP who were exposed to higher PM 2.5 (OR:1.405 [95% CI: 1.104,1.786], p=0.006*; Fig 2 ). Conclusion: Our findings suggest that ambient air pollution exposure not only associates with the CHIP prevalence but also exacerbates the risk of adverse cardiovascular events through these genetic mutations. This study highlights the importance of addressing air quality as a modifiable risk factor in the prevention of cardiovascular diseases, particularly among individuals with or at risk for CHIP.