tbuckley/cabot-search huggingface dataset:
Abstract 14188: Myopericarditis as the Initial Presentation of Systemic Lupus Erythematosus
Authors: Bistees George, Janina Quintero Bisono, Kori Ormachea, Sandeep Singh
Journal: Circulation (2023)

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disorder that can affect any organ. However, myocardial involvement is uncommon and rarely presents as the initial manifestation of SLE. Case: We present a case involving a 31-year-old male with no past medical history who presented to the emergency department with chest pain, fatigue, and intermittent swelling in his hands and feet. Initial workup was remarkable for high sensitivity troponin of 11, 821 and respiratory viral panel positive for parainfluenza. Results: Evaluation with left heart catheterization showed no obstructive coronary artery disease thus a cardiac MRI was obtained for further investigation. It showed late gadolinium enhancement involving the lateral apical wall extending to the apex as well as the lateral wall at the base (figure 1). The initial diagnosis was suspected to be viral-induced myopericarditis. However, he started developing accelerated acute kidney injury out of proportion to the current clinical presentation leading us to pursue rheumatological workup as it could explain the cardiac and renal pathologies. He was found to have ANA &gt;= 1:2560, positive dsDNA, and positive anti-smith antibody. Kidney biopsy revealed diffuse spike formation on the glomerular basement membrane and focal endocapillary proliferation and segmental sclerosis consistent with lupus nephritis. He was started on prednisone and mycophenolate mofetil resulting in symptom and disease control. Conclusion: Myocardial involvement of SLE is uncommon and can be a life-threatening condition in the acute phase; however, the disease has an overall good prognosis with early treatment.
Abstract 13070: Interleukin-19 Regulates Lymphatic Permeability and Induces Prox1-Dependent Lymphangiogenesis
Authors: Amanda Peluzzo, Cali Corbett, Amanda St. Paul, Sheri E Kelemen, Michael Autieri
Journal: Circulation (2023)

Introduction: Increased lymphangiogenesis is associated with atherosclerosis, but whether it is disease-causative or a compensatory attempt to attenuate disease is currently unresolved. Recent studies suggest lymphatic permeability plays a role in reverse cholesterol transport (RCT) as a possible mechanism for attenuating atherosclerosis. We previously reported that that Interleukin-19 (IL-19), an immunomodulatory cytokine, is unique by inducing angiogenesis while reducing atherosclerosis. The purpose of this study was to test the hypothesis that IL-19 could be atheroprotective by inducing functional lymphangiogenesis and promoting lymphatic flux. Methods &amp; Results: RNA sequencing of IL-19-treated human Lymphatic Endothelial Cells (hLEC) identified induction of chemokines, pro-lymphangiogenic, and permeability-associated genes. Prox1, the master regulator of lymphatic formation, was increased by six-fold, validated by qPCR and western blot. Cellular assays further demonstrated IL-19-associated lymphangiogenesis through hLEC proliferation, migration, and tube formation, each mitigated by Prox1 siRNA knockdown. Angpt2, a regulator of permeability through VE-cadherin, is also upregulated by IL-19 and mitigated by Prox1 siRNA knockdown. Electric Cell-substrate Impedance Sensing (ECIS) showed that IL-19 mitigates oxLDL-associated decreases in permeability, suggestive of preventing lymphatic barrier malfunction during atherosclerosis. Preliminary in vivo lymphatic permeability assays suggest injection of rmIL-19 improves lymphatic function in conditional lymphatic-specific Prox1 heterozygous mice. Conversely, similar experiments show that Il19 / LDLR double knockout mice, which are known to have exacerbated atherosclerosis, also have significantly decreased lymphatic permeability compared to LDLR -/- mice after 16-weeks of high fat diet. Conclusion: These data suggest that IL-19 is a previously unrecognized regulator of lymphatic function as it increases lymphangiogenesis and permeability, with the potential to improve RCT. Together, these effects may regulate atherosclerosis, and influence our understanding of the association between the lymphatic system and atherosclerosis.
Abstract 13079: Prevalence and Incidence of Transthyretin Amyloid Cardiomyopathy in the USA From 2004 to 2022: An Observational Database Study
Authors: Kevin M Alexander, Anne S Ersboell, Christiane L Haase, Julie T Mortensen, mathew S Maurer
Journal: Circulation (2023)

Introduction: Improved diagnosis and awareness have resulted in global increases in the incidence and prevalence of transthyretin amyloid cardiomyopathy (ATTR-CM). However, current US epidemiology data are lacking. Aims: To estimate the prevalence and incidence of ATTR-CM in a large US population and describe characteristics of patients with ATTR-CM. Methods: Data from 2004–2022 were extracted from TriNetX, a US database of EMRs covering in- and outpatient data. An algorithm using ICD-9/10 codes and RxNorm codes for clinical drugs (amyloidosis + cardiac manifestation – light chain amyloidosis) was used to identify patients with ATTR-CM. Included were adults ≥ 18 years old at index date (first ATTR-CM diagnosis per the algorithm) with ≥ 1 year of database history. The incidence and prevalence of ATTR-CM were assessed annually. Demographic characteristics at index and ATTR-CM-related comorbidities any time pre-index were assessed in cross-sectional cohorts over time. Results: In total, 12 209 patients were identified (2004–08, n = 332; 2009–13, n = 913; 2014–18, n = 3392; 2019–22, n = 7572). The incidence and prevalence of ATTR-CM per 100 000 people increased over time (incidence, 2004: 3.7; 2022: 11.5; prevalence, 2004: 5.1; 2022: 35.1) ( Figure ). Across cohorts, approximately 40% of patients were women, and 20% were Black. Median age increased over time (2004–08: 65 years; 2019–22: 74 years). In the 2019–22 cohort, the cardiac manifestations of ATTR-CM were cardiomyopathy (56.3%), atrial fibrillation (56.1%), and heart failure (20.9%). The proportion of patients with ATTR-CM-related comorbidities increased over time (2004–08 vs 2019–22: polyneuropathy, 15.1 vs 19.0%; carpal tunnel syndrome, 10.5 vs 13.4%; lumbar spinal stenosis, 4.2 vs 13.3%; aortic stenosis, 9.3 vs 13.2%). Conclusion: In this US population, the incidence and prevalence of ATTR-CM diagnoses increased over 19 years. Age at diagnosis and ATTR-CM comorbidity burden increased during this period.
Abstract 13364: Transplantation of Mutant <i>Clostridium_ASF356</i> Rescues Aging Gut-Derived Phenylacetate-Mediated Perivascular Adipose Tissue and Endothelial Senescence
Authors: Benoit Pugin, Florentin Constancias, Aurélien Thomas, Sylvain LeGludic, Meret S Allemann, Pratintip Lee, Cristina Menni, Francesco Paneni, FRANK RUSCHITZKA, Juerg H Beer, Seyed Soheil Saeedi Saravi
Journal: Circulation (2023)

Introduction: Perivascular adipose tissue (PVAT) may contribute to atherosclerosis by promoting endothelial dysfunction in aging. Gut microbiota can induce PVAT dysfunction; yet, whether it leads to endothelial cell (EC) senescence requires further investigation. Our studies revealed that gut-derived phenylacetate (PAA) and its derivative PAGln age-dependently increase ( TwinsUK Aging Cohort ). Yet, it remains unclear whether and how it contributes to PVAT-EC senescence. Methods: To circumvent our limited knowledge of PAA-(peri)vasculature pathway in aging, we performed multi-omics (fecal shotgun metagenomics and targeted metabolomics), and cell-cell (co-culture) interaction and senescence analyses. Results: Our human ( TwinsUK , n=7,303) and mouse (24 vs. 3 months, n=6) studies identified a positive association of plasma PAA and PAGln with higher abundance of VOR - and PPFOR -harboring bacteria (metabolizing dietary phenylalanine to PAA), particularly Clostridium_ASF356, in gut of old humans and mice that exhibited PVAT and vascular dysfunction. PAA aggravated PVAT dysfunction (reduced UCP1 and Prdm16) by generating excess mitochondrial H 2 O 2 and upregulating Notch1 , leading to reduced energy supply and increased senescence-messaging secretome from PVAT. It induced senescence (increased SA-β-galactosidase, telomere attrition, cell-cycle arrest ( p16 INK4a and p21 WAF1/Cip1 ), and SASP (IL6 and VCAM1)) in co-cultured aortic ECs and reduced angiogenesis (tube formation). We also showed that transplantation of genetically-engineered Δvor, Δppfor C. ASF356 double mutants to old mice (reduces plasma PAA) decreases VCAM1 secretion from PVAT and thereby inhibits senescence in aortic ECs that exhibited eNOS uncoupling. Conclusions: We conclude that age-related increase in microbiota-driven PAA regulates PVAT-mediated EC senescence via Notch1 signaling. Our bacterial engineering approach may represent a novel (peri)vascular senotherapy.
Abstract 15806: An Age Index Derived From Heart Rate Metrics is Associated With Cardiovascular Risk Biomarkers
Authors: Davide Valeriani, Hulya Emir-Farinas, Tony Faranesh
Journal: Circulation (2023)

Introduction: Conventional cardiovascular (CV) risk scores depend on clinical and laboratory measurements, and therefore have limited accessibility in the general population. Consumer wearables provide heart rate measures which individually correlate with CV risk, but it is not known how well they align collectively with conventional clinical biomarkers. Objective: To demonstrate the alignment of a composite index based on heart rate metrics available from consumer wearables with clinical biomarkers and risk scores. Methods: As chronological age is a strong predictor of cardiovascular health, we trained a linear regression model on the UK Biobank (UKB) dataset to predict chronological age from sex, body mass index, resting heart rate (RHR), and mean HR, maximum HR, HR recovery and estimated VO2max during a cycle ergometry test. Data from 53,670 individuals aged 40-70 years were used: 30,247 for training and 23,423 for testing. A cardiovascular age (CVAge) index was obtained as the difference between chronological and predicted age of the individual: a positive/negative CVAge index indicates the CV health is better/worse than the age would suggest. Heart rate predictors and CVAge index were z-scored using age and sex data on the training set. Results: Individuals in the bottom quintile (“Poor CVAge index”) of the test set had higher systolic blood pressure (+5.0 mmHg), diastolic blood pressure (+3.0 mmHg), Framingham 10-year risk score (+1.8%) and ASCVD risk score (+0.8%), than those in the top quintile (“Very Good CVAge index”) - Figure 1. Conclusions: Continuous monitoring of heart rate metrics may help users track their heart health even in the absence of clinical and laboratory measurements.
Abstract 15810: Relationship Between Left Ventricular Ejection Fraction and ICD-10 Codes Among Patients Hospitalized for Heart Failure
Authors: Ty J Gluckman, Shih-Ting Chiu, deanna Rider, Pu-kai Tseng, James Mudd, Joshua Remick, Craig Granowitz, Amy Carroll, Slaven Sikirica, Mario Enrico Canonico, Judith A Hsia, Marc P Bonaca
Journal: Circulation (2023)

Introduction: International Classification of Diseases (ICD)-10 codes are routinely used to classify patients with heart failure (HF). Although these codes play an important role with case identification and reimbursement, they are perceived to lack clinical specificity. Goals/Aims: We sought to describe the relationship between HF type (based on left ventricular ejection fraction [LVEF]) and assigned HF ICD-10 code in a large real-world dataset. Methods: We performed a retrospective cross-sectional analysis of patients admitted to a large health system within the western US between 1/1/18 and 10/1/2022 with a principal diagnosis of HF (ICD-10 codes: I50.2, systolic HF; I50.3, diastolic HF; I50.4, combined systolic and diastolic HF; I11.0, hypertensive heart disease with HF; and I13.0 and I13.2, hypertensive heart disease with HF and chronic kidney disease [CKD]). The analysis was further limited to patients with an LVEF by echocardiography in the 3 months preceding hospital discharge. Results: Over nearly 5 years, 61,238 HF hospitalizations occurred, of which 49,772 (81%) had an LVEF available. Most patients admitted with systolic HF (4.4% of the cohort) as well as systolic and diastolic HF (3.2% of the cohort) had an LVEF ≤40% (86.2% and 74.8%, respectively); similarly, most patients admitted with diastolic HF (3.1% of the cohort) had an LVEF ≥50% (94.0%) (Figure). Those admitted with hypertensive heart disease with HF (36.3% of the cohort) and hypertensive heart disease with HF and CKD (52.9% of the cohort) had a much wider LVEF distribution (Figure). Conclusions: Although relatively good concordance was noted between LVEF and ICD-10 codes for systolic HF, diastolic HF, and systolic and diastolic HF, this was not the case for most HF hospitalizations. This should be considered when performing analyses with HF ICD-10 codes.
Abstract 13114: Beyond the Medical Record: An In-Depth Exploration of Takotsubo Syndrome Triggers
Authors: Natalie G Keirns, Rochelle Rosen, Matthew Burg, Sara Ouaddi, Emma Black, Janice Tripolone, Christopher Breault, Jinnette D Abbott, Elena Salmoirago-Blotcher
Journal: Circulation (2023)

Introduction: Takotsubo syndrome (TS) is an acute, reversible episode of systolic dysfunction, preceded by emotional/physical triggers in 2/3 of cases and no trigger in 1/3 of cases based on retrospective medical record data. Research Question: How do patients with a recent TS episode describe their triggers? Goals: To conduct an in-depth investigation of patient narratives concerning the events that triggered their TS episode. Methods: We conducted semi-structured interviews in patients with a recent (&lt; 1 month) TS episode (Mayo Clinic criteria). We inquired about (1) type of trigger(s), and (2) trigger timing (&lt; or &gt; 48-96 hours before TS episode). Triggers were coded as emotional, psychosocial, and/or behavioral/physical. Recordings were transcribed, coded, summarized, and analyzed by the first and second authors. Results: Over 2/3 of patients (n=30; 97% female, 93% white; age 64 ± 9 yrs old) identified a trigger. Triggers included: a) acute events that occurred &lt;48-96 hours before the TS episode (e.g., death of daughter), b) chronic circumstances that occurred both outside of and within 48-96 hours before the episode (e.g., conflicts with spouse), and c) acute events that occurred &gt;48-96 hours before (e.g., binge drinking). The most prevalent triggers were negative emotions (86%; e.g., stress) and behavioral or physical factors (81%; e.g., atypical exercise/exertion). Nearly all triggers reported (81%) were multi-factorial (e.g., both physical and emotional). Of note, among participants who initially did not identify a trigger, 67% described potential triggering factors during the interview (e.g., increased stress). Conclusions: Consistent with the literature, 2/3 of patients identified a trigger. Yet, in contrast with current evidence, triggers were most often multifactorial (e.g., both emotional and physical) and many were chronic/ongoing. Moreover, for participants who could not identify a trigger, a potential trigger was often identified in the interview. Patients’ narratives around TS triggers are highly complex and likely insufficiently captured in clinical encounters. If these findings are replicated in larger and more diverse samples, they could lead to a re-thinking of the role of triggers in the onset of TS.
Abstract 14195: Right Ventricular Outflow Tract Diameter Increase With the Low-Moderate Workload: A Prospective Simultaneous Exercise Echocardiography and Invasive Cardiopulmonary Exercise Testing Study
Authors: Ahmed ElShaer, Mariana Garcia-Arango, Claudia E Korcarz, Farhan Raza
Journal: Circulation (2023)

Background: While cardiac output at rest can be estimated non-invasively with echocardiogram, change in left ventricular or right ventricular outflow tract diameter (RVOTd) with exercise makes the cardiac output estimation inaccurate. Hypothesis: RVOTd increases with exercise proportionally with an incremental workload and is determined by stroke volume augmentation. Aims: 1. Define a workload-based change in RVOTd in subjects undergoing invasive cardiopulmonary exercise test (iCPET). 2. Correlate RVOTd at exercise stages with iCPET metrics. Methods: 20 subjects undergoing simultaneous echocardiogram and iCPET were enrolled in a prospective study. Exercise datapoints were acquired at 25 W (n=20), 50W (n=16), 75W (n=14), 100W (n=6). Three hemodynamic groups included: HFpEF (n=12), PAH (n=5), controls (n=3). Utilizing iCPET-based direct Fick cardiac output and stroke volume, RVOTd was reverse engineered with RVOT velocity time integral, per ASE guidelines. Pearson correlation was used to assess correlation of RVOTd with hemodynamic metrics. p&lt;0.05* Results: In overall cohort, age was 64±12 years, BMI 31.2±4.9 Kg/m 2 , female 60%, peak VO 2 13.7±5.7 mL/Kg.min -1 and V E /VCO 2 37±8. Increase in RVOTd with exercise is represented in the Figure. In comparison to rest, RVOTd increased significantly even at low-25W (+4.1±13.6%*) and moderate-50W (+7.6±17.2%*) workloads. Overall, RVOTd increased by 4-5% every 25W. At high workload (100W), the diameter increased by 24% (n=6). There were no differences in RVOT diameter between subgroups. RVOTd at four exercise stages (25W, 50W, 75W, 100W) correlated significantly with stroke volume index (r=0.68*, 0.80*, 0.23, 0.64) and cardiac output (r=0.50*, 0.80*, 0.08, 0.68), but non-significantly with heart rate (r=-0.15, 0.19, -0.10, 0.68). Conclusion: RVOTd increases by 4-5% every 25W on an incremental workload protocol. This behavior is predominantly associated with an increase in stroke volume index with exercise.
Abstract 15554: Three-Year Incidence of Pacemaker Implantation in Patients With Atrial Fibrillation and Sinus Node Dysfunction Receiving Ablation versus Antiarrhythmic Drugs
Authors: nazli okumus, Maximiliano Iglesias, Rahul Khanna, Yiran Rong, Saima Karim
Journal: Circulation (2023)

Introduction: Around one in five patients with atrial fibrillation (AF) has a diagnosis of sinus node dysfunction (SND). Hypothesis: There will be lower incidence of pacemaker implantation (PPM) among patients with AF and SND who undergo catheter ablation (CA) compared to anti-arrhythmic drugs (AAD). Methods: Data were collected from 2014-2022 utilizing Optum Clinformatics database, an administrative claims database for commercially insured and Medicare Advantage beneficiaries in the United States. Adult patients with concomitant AF and SND, and prior history of taking at least one AAD were identified and classified into CA or AAD cohort based for subsequent treatment. Patients were excluded if they had a prior history of PPM, implantable cardiac defibrillator, catheter or surgical ablation, AV nodal ablation, valvular procedure, left atrial appendage occlusion, or high grade/complete heart block. Inverse probability treatment weighting technique was applied to balance sociodemographic and clinical comorbid characteristics between the cohorts. Weighted Cox regression model was used to evaluate the differential risk of incident PPM. Sub-analyses were performed by AF type (paroxysmal and persistent AF). Results: There were 1,206 patients in AAD cohort and 1,624 patients in CA cohort. Incidence rate (per 1,000 person-year) of PPM was 55.8 (95% CI 47.1-64.5) for CA cohort and 117.8 (95% CI 101.7-133.9) for AAD cohort and the 3-year cumulative incidence of PPM was 23.1% (95% CI 20.0%-26.2%) and 13.8% (95% CI 11.6%-15.9%), respectively. Weighted Cox regression model indicated that CA had 43% lower risk of incident PPM compared to AADs (hazard ratio [HR] 0.57; 95% CI 0.46-0.71). Those with paroxysmal AF (HR 0.48; 95% CI 0.34-0.69) had lower need for PPM compared to persistent AF (HR 0.57; 95% CI 0.40-0.81). Conclusions: Patients with AF and SND treated with CA were observed to have significantly lower risk of incident pacemaker implantation compared to those who had AAD.
Abstract 13085: Sociodemographic Predictors of NYHA Class Assignment: An Analysis From CHAMP-HF
Authors: Charles F Sherrod, Mirza Khan, Kensey L Gosch, Paul S Chan, Andrew J Sauer, Javed Butler, Stephen J Greene, Nancy M Albert, Gregg C Fonarow, John A Spertus
Journal: Circulation (2023)

Background: The New York Heart Association (NYHA) class is the cornerstone of health status assessment in heart failure with reduced ejection fraction (HFrEF). However, prior work has shown marked variability compared to patient-reported health status - measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). As clinicians determine NYHA, systemic biases may impact class selection. It is unknown if patients’ age, race, sex, BMI, or education influence NYHA class assignment. Aims: To determine whether patient factors (age, race, sex, education, and BMI) predict NYHA class when controlling for KCCQ. Methods: Participants in CHAMP-HF, a prospective registry of ambulatory HFrEF patients, were evaluated by a clinician with a simultaneously completed NYHA and KCCQ-12. Using hierarchical multinomial logistic regression models with site-level random effects to account for clustering by site, we modeled NYHA class on age, Hispanic and Black vs White patients, males vs females, education, and BMI separately while adjusting for baseline KCCQ-12 as a restricted cubic spline. Results: 4,742 participants were included. The table shows model summaries. Of all predictor variables, only age was associated with differential NYHA class assignment. Compared with class I, 5-year increases in age increased the odds of being assigned class II (OR 1.11; 95% CI 1.07-1.16), III (OR 1.2; 95% CI 1.15-1.26) and IV (OR 1.18; 95% CI 1.07-1.31). Conclusions: These results suggest clinicians assign higher NYHA classes to older patients irrespective of patient-reported health status, but there were no differences identified by race, sex, education or BMI. Whether this leads to differential treatment in older patients merits investigation.